| 1. |
- Khorram-Manesh, Amir, 1958, et al.
(författare)
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Long-term outcome of a large series of patients surgically treated for pheochromocytoma
- 2005
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Ingår i: Journal of internal medicine. - 0954-6820. ; 258:1, s. 55-66
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyse the morbidity, mortality and long-term outcome in a consecutive series of surgically treated patients with pheochromocytoma (PC), or paraganglioma (PG), from the western region of Sweden between 1950 and 1997. PATIENTS: All patients (n = 121) who had been hospitalized and treated for PC/PG over 47 years. DESIGN: Retrospective review of patients with PC/PG regarding presenting symptoms, tumour characteristics, clinical management and long-term outcome after treatment. SETTING: One referral centre for all patients from the western region of Sweden. RESULTS: During an observation of 15 +/- 6 years, 42 patients died vs. 23.6 expected in the general population (P < 0.001). There was no intra- or post-operative mortality. Four patients with sporadic disease died of malignant PC and six with hereditary disease of associated neuroectodermal tumours. Five patients died of other malignancies, 20 of cardiovascular disease and seven of other causes. Besides older age at primary surgery, elevated urinary excretion of methoxy-catecholamines was the only observed risk factor for death (P = 0.02). At diagnosis 85% of the patients were hypertensive; one year after surgery more than half were still hypertensive. However, pre- and post-operative hypertension did not influence the risk for death versus controls. CONCLUSION: Pheochromocytoma/PG can be safely treated by surgery. Death of malignant PC/PG was unusual, but the patients as a group had an increased risk of death. We recommend life-long follow-up of patients treated for PC/PG with screening for recurrent tumour in sporadic cases and for associated tumours in hereditary cases. This strategy would also be helpful in diagnosing cardiovascular disease at an early stage.
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| 2. |
- Anckarsäter, Henrik, 1966, et al.
(författare)
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Child neurodevelopmental and behavioural problems are intercorrelated and dimensionally distributed in the general population
- 2008
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Ingår i: The Open Psychiatry Journal. - : Bentham Science Publishers Ltd.. - 1874-3544. ; 2, s. 5-11
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Tidskriftsartikel (refereegranskat)abstract
- The Autism – Tics, AD/HD, and other Comorbidities inventory (A-TAC) is a comprehensive interview for evaluating problems related to autism spectrum disorders (ASD), tic disorders, attention-deficit/hyperactivity disorder (AD/HD), and common comorbid conditions in children and adolescents. A-TAC telephone interviews were administered to parents of 2,957 children aged nine- or twelve-years, representing one in each twin pair included in the population- based Child and Adolescent Twin Study in Sweden (CATSS). A total of 16.4% were screen-positive for one or several of the targeted disorder, 1.3% for ASD and 5.6% for AD/HD. All types of problems were more common among boys, with the exception of those related to “eating habits”. They were all dimensionally/continuously distributed, highly inter-correlated, and overlapped across types. They aggregated in three ba- sic factors corresponding to externalizing/disruptiveness, socio-communicative problems, and compulsiveness. Population-based data on problems in children thus challenge current categorical diagnostic definitions, calling for dimen- sional and complementary models of problem descriptions.
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| 3. |
- Bergendorff, Ola, et al.
(författare)
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Chemical changes in rubber allergens during vulcanization
- 2007
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 57:3, s. 152-157
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Tidskriftsartikel (refereegranskat)abstract
- Allergic contact dermatitis to rubber is caused by residues of chemicals used in manufacturing a rubber product. Several different additives are used to achieve a final product of the desired characteristics. Accelerators such as thiurams, dithiocarbamates, and mercaptobenzothiazoles are often among the additives responsible for allergic reactions recognized by dermatologists. The chemistry of the vulcanization process is complicated; as it occurs at an elevated temperature with a mixture of reactive chemicals, the compositions of the initial and final products differ. This paper investigates the changes in composition of common allergens during vulcanization, doing so by chemically analysing various rubber formulations at different stages of the process. Major changes were found in which added chemicals were consumed and new ones produced. An important observation is that thiuram disulfides rarely appear in the final rubber although they may have been used as additives. Instead, thiurams are often converted to dithiocarbamates or to products formed by addition to mercaptobenzothiazole structures, if these have been used together with thiurams as accelerators.
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| 4. |
- Bergendorff, Ola, et al.
(författare)
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Contact dermatitis to a rubber allergen with both dithiocarbamate and benzothiazole structure.
- 2007
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 56:5, s. 278-280
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Tidskriftsartikel (refereegranskat)abstract
- Contact dermatitis to rubber products are often caused by additives used during manufacture, and diagnosed from patch test with established rubber allergen series. In these series the compounds are divided into separate groups such as thiurams, dithiocarbamates and mercaptobenzothiazoles. The objectives were to investigate the substances with allergenic structures present in a diving mask giving rise to facial dermatitis, also those substances including structures from different groups of rubber chemicals. The rubber material was analysed by high-performance liquid chromatography and diode-array detector. The patient was tested by epicutaneous tests using pure substances, extracts and authentic rubber material. 2-Benzothiazolyl-N,N-diethylthiocarbamylsulfide, was found in the diving mask and the patient showed positive reaction to the pure compound and to extracts of the diving mask. This compound has structures of both mercaptobenzothiazole and thiuram/dithiocarbamate in its formulae. Besides the established groups of rubber accelerators, uncommon allergens with structures from more than one group can be formed or added at vulcanization. Chemical analysis of the product is needed to find these allergens.
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| 5. |
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Fernandez, Celine, et al.
(författare)
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Hormone-sensitive lipase is necessary for normal mobilization of lipids during sub-maximal exercise.
- 2008
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Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 295, s. 179-186
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Tidskriftsartikel (refereegranskat)abstract
- For the working muscle there are a number of fuels available for oxidative metabolism, including glycogen, glucose and non-esterified fatty acids. Non-esterified fatty acids originate from lipolysis in white adipose tissue, from hydrolysis of VLDL-triglycerides or from hydrolysis of intramyocellular triglyceride stores. A key enzyme in the mobilization of fatty acids from intracellular lipid stores is hormone-sensitive lipase (HSL). The aim of the present study was to investigate the metabolic response of HSL-null mice challenged with exercise or fasting and to examine if other lipases are able to fully compensate for the lack of HSL. The results showed that HSL-null mice have reduced capacity to perform aerobic exercise. The liver glycogen stores were more rapidly depleted in HSL-null mice during treadmill exercise and HSL-null mice had reduced plasma concentrations of both glycerol and non-esterified fatty acids after exercise and fasting, respectively. The data support the hypothesis that in the absence of HSL mice are not able to respond to an exercise challenge with increased mobilization of the lipid stores. Consequently, the impact of the lipid sparing effect on liver glycogen will be reduced in the HSL-null mice, resulting in faster depletion of this energy source, contributing to the decreased endurance during sub-maximal exercise. Key words: Treadmill exercise, lipid metabolism, glycogen, skeletal muscle, liver.
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| 10. |
- Gustafsson, Johanna, et al.
(författare)
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Predictors of the first cardiovascular event in patients with systemic lupus erythematosus : a prospective cohort study
- 2009
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 11:6, s. R186-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION :Cardiovascular disease (CVD) is a major cause of premature mortality among Systemic lupus erythematosus (SLE) patients. Many studies have measured and evaluated risk factors for premature subclinical atherosclerosis, but few studies are prospective and few have evaluated risk factors for hard endpoints, i.e. clinically important cardiovascular events (CVE). We investigated the impact of traditional and lupus associated risk factors for the first ever CVE in a longitudinal cohort of SLE patients.METHODS : A total of 182 SLE patients (mean age 43.9 years) selected to be free of CVE were included. Cardiovascular and autoimmune biomarkers were measured on samples collected after overnight fasting at baseline. Clinical information was collected at baseline and at follow up. End point was the first ever CVE (ischemic heart, cerebrovascular or peripheral vascular disease or death due to CVD). Impact of baseline characteristics/biomarkers on the risk of having a first CVE was evaluated with Cox regression.RESULTS :Follow up was 99.5% after a mean time of 8.3 years. Twenty-four patients (13%) had a first CVE. In age-adjusted Cox regression, any positive antiphospholipid antibody (aPL), elevated markers of endothelial activation (von Willebrand factor (vWf), soluble vascular cellular adhesion molecule-1 (sVCAM-1)) and fibrinogen predicted CVEs. Of SLE manifestations, arthritis, pleuritis and previous venous occlusion were positively associated with future CVEs while thrombocytopenia was negatively associated. Among traditional risk factors only age and smoking were significant predictors. In a multivariable Cox regression model age, any positive aPL, vWf and absence of thrombocytopenia were all predictors of the first CVE.CONCLUSIONS : In addition to age, positive aPL, biomarkers indicating increased endothelial cell activity/damage, and absence of thrombocytopenia were independent predictors of CVEs in this prospective study. Our results indicate that activation of the endothelium and the coagulation system are important features in SLE related CVD. Furthermore, we observed that the risk of CVEs seems to differ between subgroups of SLE patients.
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| 11. |
- Hansson, Gustav, 1977, et al.
(författare)
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Country Size and the Rule of Law: Resuscitating Montesquieu
- 2006
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The political and economic impact of country size has been a frequently discussed issue in social science. In accordance with the general hypothesis of Montesquieu, this paper demonstrates that there is a robust negative relationship between the size of country territory and a measure of the rule of law for a large cross-section of countries. We propose that there are two main reasons for this regularity; firstly that institutional quality often has the character of a local public good that is imperfectly spread across space from the capital to the hinterland, and secondly that a large territory usually is accompanied by valuable rents that tend to distort property rights institutions. Our empirical analysis further shows that whether the capital is centrally or peripherally located within the country matters for the average level of rule of law.
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| 12. |
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| 13. |
- Hansson, Ola
(författare)
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Hormone-Sensitive Lipase, new roles for an old enzyme
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hormone-sensitive lipase (HSL) has a wide tissue distribution with the highest expression found in white adipose tissue (WAT). HSL also has a unique ability to hydrolyze a large panel of substrates including acylglycerols, cholesteryl esters and retinyl esters. HSL is potentially a new drug target for the treatment of obesity and type II diabetes. However, as HSL is not only expressed in adipose tissue, but also plays significant roles in other tissues it is of importance to better understand the different functions of this enzyme in the body. In this thesis the aim has been to study the consequences of a targeted disruption of the HSL gene in the mouse with focus on the effects in skeletal muscle and WAT. Expressional and functional analyses of soleus muscle of HSL null mice supports an important role of HSL in skeletal muscle metabolism as the absence of HSL leads to increased glycogen utilization and an increased amount of lipid droplets, which presumably reflects a metabolic switch from lipid to carbohydrate metabolism. A fibre type transformation from slow twitch oxidative fibres to an enrichment of fast twitch glycolytic fibres in soleus muscle is also suggested. Using a proteomic approach a local inflammatory response in WAT is demonstrated in the non-obese HSL null mouse model. New methodological aspects of analysing data generated by two-dimensional polyacrylamide gel electrophoresis are also presented. Increased energy expenditure and perturbation of adipogenesis are suggested reasons behind the observed protection against diet-induced obesity in HSL null mice. Results presented in this thesis suggest an important role of HSL in lipid signalling and adipogenesis through its action as a retinyl ester hydrolase in WAT.
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| 14. |
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| 15. |
- Hansson, Ola, et al.
(författare)
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Transcriptome and proteome analysis of soleus muscle of hormone-sensitive lipase-null mice
- 2005
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Ingår i: Journal of Lipid Research. - 1539-7262. ; 46:12, s. 2614-2623
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Tidskriftsartikel (refereegranskat)abstract
- Hormone-sensitive lipase (HSL), a key enzyme in fatty acid mobilization in adipocytes, has been demonstrated also in skeletal muscle. To gain further insight into the role and importance of HSL in skeletal muscle, a transcriptome analysis of soleus muscle of HSL-null mice was performed. A total of 161 transcripts were found to be differentially expressed. Increased mRNA levels of fructose-1,6-bisphosphatase, fructose-2,6-bisphosphatase, and phosphorylase kinase gamma 1A suggest a higher glycogen flux in soleus muscle of HSL-null mice. An observed increase in the utilization of glycogen stores supports this finding. Moreover, an increased amount of intramyocellular lipid droplets, observed by transmission electron microscopy, suggests decreased mobilization of lipid stores in HSL-null mice. To complement the transcriptome data, protein expression analysis was performed. Five spots were found to be differentially expressed: pyruvate dehydrogenase E1 alpha, creatine kinase (CK), ankyrin-repeat domain 2, glyceraldehyde-3-phosphate dehydrogenase, and one protein yet to be identified. The increased protein level of CK indicates creatine phosphate degradation to be of increased importance in HSL-null mice. The results of this study suggest that in the absence of HSL, a metabolic switch from reliance on lipid to carbohydrate energy substrates takes place, supporting an important role of HSL in soleus muscle lipid metabolism.
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| 16. |
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| 17. |
- Henriksson, Dan, et al.
(författare)
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Tools for Real-Time Control Systems Co-Design
- 2006
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Ingår i: ARTES -- A network for Real-Time research and graduate Education in Sweden 1997--2006.
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Bokkapitel (refereegranskat)abstract
- A survey of four co-design tools for joint analysis, simulation, and design of computer-based control systems developed within the Swedish ARTES programme is presented. The tools allow simultaneous treatment of the control aspects and the computing and communication aspects of the control problems. The tools are Jitterbug and TrueTime developed at the Department of Automatic Control LTH, Lund University, and Aida and Xilo developed at the Division of Mechatronics, Department of Machine Elements, KTH.
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| 18. |
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| 19. |
- Markus, Tina, et al.
(författare)
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Cerebral Inflammatory Response after Fetal Asphyxia and Hyperoxic Resuscitation in Newborn Sheep.
- 2007
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Ingår i: Pediatric Research. - 1530-0447. ; 62, s. 71-77
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Tidskriftsartikel (refereegranskat)abstract
- Resuscitation with pure oxygen at birth after fetal asphyxia may aggravate brain damage by inducing pro-inflammation. The toll-like receptors (TLRs) may serve a pro-inflammatory role in hyperoxemia during ischemia-reperfusion. Sixteen near-term fetal sheep (132-136 d) were subjected to 10 min of cord occlusion, delivery and mechanical ventilation with 100% O-2 (n = 8), or 21% O-2 (n = 8) for 30 min followed by normoxemia for 90 min. Eight sheep fetuses were delivered immediately with inspired O-2 targeted at normoxemia for 120 min (controls). Levels and distributions of mRNAs for IL-1 beta, TNF-alpha, IL-12p40, IL-18, IL-6, IL-10, IFN-gamma, TLR-2. -3 and -4 in cerebral tissue at 2 h after birth were evaluated with real-time polymerase chain reaction (PCR) and in situ hybridization. Expressions of IL-1 beta, IL-12p40, TLR-2, and TLR-4 were increased in cortex/subcortex after resuscitation with 100% 02 compared with 21% O-2 (all p < 0.05) and to controls (all p < 0.05). Increased cellular expression of IL-1 beta was localized to sub-meningeal cortical layers and to sub-cortical white matter. Hyperoxic resuscitation at birth following fetal asphyxia induces a cerebral pro-inflammatory response with an up-regulation of TLR-2 and -4. These may be early events leading to increased tissue damage after exposure to hyperoxemia at birth.
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| 20. |
- Naucler, Pontus, et al.
(författare)
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Efficacy of HPV DNA testing with cytology triage and/or repeat HPV DNA testing in primary cervical cancer screening.
- 2009
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 101:2, s. 88-99
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Tidskriftsartikel (refereegranskat)abstract
- Primary cervical screening with both human papillomavirus (HPV) DNA testing and cytological examination of cervical cells with a Pap test (cytology) has been evaluated in randomized clinical trials. Because the vast majority of women with positive cytology are also HPV DNA positive, screening strategies that use HPV DNA testing as the primary screening test may be more effective.
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| 21. |
- Naucler, Pontus, et al.
(författare)
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Human papillomavirus and Papanicolaou tests to screen for cervical cancer.
- 2007
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Ingår i: New England Journal of Medicine. - Boston, Massachusetts : Massachusetts medical society. - 0028-4793 .- 1533-4406. ; 357:16, s. 1589-97
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Tidskriftsartikel (refereegranskat)abstract
- Background Screening for cervical cancer based on testing for human papillomavirus (HPV) increases the sensitivity of detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia, but whether this gain represents overdiagnosis or protection against future high-grade cervical epithelial neoplasia or cervical cancer is unknown. Methods In a population-based screening program in Sweden, 12,527 women 32 to 38 years of age were randomly assigned at a 1:1 ratio to have an HPV test plus a Papanicolaou (Pap) test (intervention group) or a Pap test alone (control group). Women with a positive HPV test and a normal Pap test result were offered a second HPV test at least 1 year later, and those who were found to be persistently infected with the same high-risk type of HPV were then offered colposcopy with cervical biopsy. A similar number of double-blinded Pap smears and colposcopies with biopsy were performed in randomly selected women in the control group. Comprehensive registry data were used to follow the women for a mean of 4.1 years. The relative rates of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected at enrollment and at subsequent screening examinations were calculated. Results At enrollment, the proportion of women in the intervention group who were found to have lesions of grade 2 or 3 cervical intraepithelial neoplasia or cancer was 51% greater (95% confidence interval [CI], 13 to 102) than the proportion of women in the control group who were found to have such lesions. At subsequent screening examinations, the proportion of women in the intervention group who were found to have grade 2 or 3 lesions or cancer was 42% less (95% CI, 4 to 64) and the proportion with grade 3 lesions or cancer was 47% less (95% CI, 2 to 71) than the proportions of control women who were found to have such lesions. Women with persistent HPV infection remained at high risk for grade 2 or 3 lesions or cancer after referral for colposcopy. Conclusions The addition of an HPV test to the Pap test to screen women in their mid-30s for cervical cancer reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening examinations.
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| 22. |
- Osmark, Peter, et al.
(författare)
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Unique splicing pattern of the TCF7L2 gene in human pancreatic islets.
- 2009
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 52, s. 850-854
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Intronic variation in the TCF7L2 gene exhibits the strongest association to type 2 diabetes observed to date, but the mechanism whereby this genetic variation translates into altered biological function is largely unknown. A possible explanation is a genotype-dependent difference in the complex splicing pattern; however, this has not previously been characterised in pancreatic or insulin target tissues. Here, the detailed TCF7L2 splicing pattern in five human tissues is described and dependence on risk genotype explored. METHODS: RT-PCR and quantitative real-time PCR were employed to characterise TCF7L2 splicing in pancreatic islets, blood lymphocytes, skeletal muscle and subcutaneous and visceral adipose tissue from non-diabetic individuals. RESULTS: The mapping of TCF7L2 splice variants shows a specific pattern in pancreatic islets, with four predominant transcripts and high usage of the variable exons 4 and 15. The overall concentration of TCF7L2 mRNA is highest in islets and fat and lower in blood and muscle. No significant difference in overall amount or splicing pattern was observed between carriers and non-carriers of the rs7903146 risk (T) allele. However, incorporation of exon 4 in islets correlates positively with plasma HbA(1c) levels (r = 0.758; p = 0.018). CONCLUSIONS/INTERPRETATION: There were pronounced tissue-specific differences in the splicing of TCF7L2 with forms containing exon 4 and 15 being most abundant in islets. The incorporation of exon 4 in islets correlated with HbA(1c) levels. Further experiments will be needed to determine the direction of this correlation, and larger cohorts needed to unequivocally resolve whether there is a relationship between genotype and splicing in islets.
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| 23. |
- Prokunina-Olsson, Ludmila, et al.
(författare)
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Tissue-specific alternative splicing of TCF7L2
- 2009
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 18:20, s. 3795-3804
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Tidskriftsartikel (refereegranskat)abstract
- Common variants in the transcription factor 7-like 2 (TCF7L2) gene have been identified as the strongest genetic risk factors for type 2 diabetes (T2D). However, the mechanisms by which these non-coding variants increase risk for T2D are not well-established. We used 13 expression assays to survey mRNA expression of multiple TCF7L2 splicing forms in up to 380 samples from eight types of human tissue (pancreas, pancreatic islets, colon, liver, monocytes, skeletal muscle, subcutaneous adipose tissue and lymphoblastoid cell lines) and observed a tissue-specific pattern of alternative splicing. We tested whether the expression of TCF7L2 splicing forms was associated with single nucleotide polymorphisms (SNPs), rs7903146 and rs12255372, located within introns 3 and 4 of the gene and most strongly associated with T2D. Expression of two splicing forms was lower in pancreatic islets with increasing counts of T2D-associated alleles of the SNPs: a ubiquitous splicing form (P = 0.018 for rs7903146 and P = 0.020 for rs12255372) and a splicing form found in pancreatic islets, pancreas and colon but not in other tissues tested here (P = 0.009 for rs12255372 and P = 0.053 for rs7903146). Expression of this form in glucose-stimulated pancreatic islets correlated with expression of proinsulin (r(2) = 0.84-0.90, P < 0.00063). In summary, we identified a tissue-specific pattern of alternative splicing of TCF7L2. After adjustment for multiple tests, no association between expression of TCF7L2 in eight types of human tissue samples and T2D-associated genetic variants remained significant. Alternative splicing of TCF7L2 in pancreatic islets warrants future studies. GenBank Accession Numbers: FJ010164-FJ010174.
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| 24. |
- Resjö, Svante, et al.
(författare)
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Proteomic studies in animal models of diabetes
- 2008
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Ingår i: Proteomics Clinical Applications. - : Wiley. - 1862-8354 .- 1862-8346. ; 2:5, s. 654-669
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Forskningsöversikt (refereegranskat)abstract
- The aim of this review is to provide an overview of proteomic studies in animal models of diabetes and to give some insight into the different methods available today in the rapidly developing field of proteomics. A summary of 31 papers published between 1997 and 2007 is presented. For instance, proteomics has been used to study the development of both type 1 and type 2 diabetes, diabetic complications in tissues like heart, kidney and retina and changes after treatment with anti-diabetic drugs like peroxisome proliferator-activated receptors agonists. Together, these studies give a good overview of a number of experimental approaches. Proteomics holds the promise of providing major contributions to the field of diabetes research. However, to achieve this, a number of issues need to be resolved. Appropriate data representation to facilitate data comparison, exchange, and verification is required, as well as improved statistical assessment of proteomic experiments. In addition, it is important to follow up the results with functional studies to be able to make biologically relevant conclusions. The potential of proteomics to dissect complex human disorders is now beginning to be realized. In the future, this will result in new important information concerning diabetes.
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| 25. |
- Rönn, Tina, et al.
(författare)
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Age influences DNA methylation and gene expression of COX7A1 in human skeletal muscle.
- 2008
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 51:7, s. 1159-1168
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Reduced oxidative capacity of the mitochondria in skeletal muscle has been suggested to contribute to insulin resistance and type 2 diabetes. Moreover, a set of genes influencing oxidative phosphorylation (OXPHOS) is downregulated in diabetic muscle. Here we studied whether genetic, epigenetic and non-genetic factors influence a component of the respiratory chain, COX7A1, previously shown to be downregulated in skeletal muscle from patients with type 2 diabetes. The specific aims were to: (1) evaluate the impact of genetic (single nucleotide polymorphisms [SNPs]), epigenetic (DNA methylation) and non-genetic (age) factors on the expression of COX7A1 in human skeletal muscle; and (2) investigate whether common variants in the COX7A1 gene are associated with increased risk of type 2 diabetes. METHODS: COX7A1 mRNA expression was analysed in muscle biopsies from young (n = 110) and elderly (n = 86) non-diabetic twins and related to measures of in vivo metabolism. Genetic variants (three SNPs) from the COX7A1 locus were genotyped in the twins and in two independent type 2 diabetes case-control cohorts (n = 1466 and 6380, respectively). DNA methylation of the COX7A1 promoter was analysed in a subset of twins (ten young, ten elderly) using bisulphite sequencing. RESULTS: While DNA methylation of the COX7A1 promoter was increased in muscle from elderly compared with young twins (19.9 +/- 8.3% vs 1.8 +/- 2.7%; p = 0.035), the opposite was found for COX7A1 mRNA expression (elderly 1.00 +/- 0.05 vs young 1.68 +/- 0.06; p = 0.0005). The heritability of COX7A1 expression was estimated to be 50% in young and 72% in elderly twins. One of the polymorphisms investigated, rs753420, influenced basal COX7A1 expression in muscle of young (p = 0.0001) but not of elderly twins. The transcript level of COX7A1 was associated with increased in vivo glucose uptake and [Formula: see text] (p = 0.009 and p = 0.001, respectively). We did not observe any genetic association between COX7A1 polymorphisms and type 2 diabetes after correcting for multiple testing. CONCLUSIONS/INTERPRETATION: Our results provide further evidence for age as a factor influencing DNA methylation and expression of OXPHOS genes, and thereby in vivo metabolism.
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