| 1. |
- Merwood, Andrew, et al.
(författare)
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Genetic associations between the ADHD symptom dimensions and Cloninger's temperament dimensions in adult twins
- 2013
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Ingår i: European Neuropsychopharmacology. - Amsterdam, Netherlands : Elsevier. - 0924-977X .- 1873-7862. ; 23:6, s. 416-425
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have identified phenotypic associations between Cloninger's temperament dimensions and the symptoms of attention deficit hyperactivity disorder (ADHD) in adults. However the underlying aetiology of these associations remains unclear. We investigate the extent to which genetic and environmental influences contribute to the relationship between temperament and ADHD, examining the ADHD symptoms of inattention (IA) and hyperactivity/impulsivity (HI) separately. Participants were 886 adult twin pairs aged 19-20 years. ADHD symptoms of IA and HI were measured using a DSM-IV based rating scale. Temperament was measured using Cloninger's Temperament and Character Inventory (TCI), across four dimensions: novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (PS). The twin method was used to decompose phenotypic variance/covariance among these variables into genetic and environmental components. We found that NS was genetically associated with both ADHD symptom dimensions (IA and HI), but that HA was genetically associated with IA only. There was also some evidence of genetic association between PS, IA and HI. These findings suggest that unique profiles of temperament are genetically related to the two ADHD symptom dimensions in adults. Further work is now needed to elucidate the mechanisms that underlie both the combined and separate symptom factor domains of ADHD.
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| 2. |
- Fransén, Karin, 1973-, et al.
(författare)
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CRP levels are significantly associated with CRP genotype and estrogen use in The Lifestyle, Biomarker and Atherosclerosis (LBA) study
- 2022
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Ingår i: BMC Cardiovascular Disorders. - : BioMed Central. - 1471-2261 .- 1471-2261. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The C‑reactive protein (CRP) is an important biomarker for atherosclerosis and single nucleotide poly‑morphisms (SNPs) in the CRP locus have been associated with altered CRP levels and associated with risk for cardio‑vascular disease. However, the association between genetic variations in the CRP gene, estrogen use and CRP levels orearly signs of atherosclerosis in young healthy individuals is not fully characterized. We aimed to evaluate the influ‑ence of five genetic variants on both plasma CRP levels and carotid intima‑media thickness (cIMT) values, includingaspects on estrogen containing contraceptive use in females.Methods: Genotyping was performed with TaqMan real time PCR and compared with high sensitivity CRP serumlevels in 780 Swedish young, self‑reported healthy individuals. Haplotypes of the SNPs were estimated with the PHASEv 2.1. The cIMT was measured by 12 MHz ultrasound. The contraceptive use was self‑reported.Results: Strong associations between CRP and genotype were observed for rs3091244, rs1800947, rs1130864, andrs1205 in women (all p < 0.001). In men, only rs1800947 was associated with CRP (p = 0.029). The independent effectof genotypes on CRP remained significant also after adjustment for established risk factors. Female carriers of the H1/ATGTG haplotype had higher CRP than non‑carriers. This was specifically pronounced in the estrogen‑using group(p < 0.001), and they had also higher cIMT (p = 0.002) than non‑carriers but with a small cIMT difference between thehaplotype groups (0.02 mm). In parallel, a significant correlation between CRP and cIMT in the estrogen using groupwas observed (r = 0.194; p = 0.026).Conclusions: Estrogen use, genotypes and haplotypes in the CRP locus are significantly associated with CRP levels.Based on an observed interaction effect between sex/estrogen use and the H1/ATGTG haplotype on CRP, and amarginally thicker cIMT in the estrogen using group, our data suggest that both genotypes and estrogen usage couldbe involved in arterial wall structural differences. The causality between CRP levels and cIMT remains unclear, and theobserved difference in cIMT is not clinically relevant in the present state. Future larger and longitudinal studies mayshed further light on the role of more long‑term estrogen use and early atherosclerosis.
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| 3. |
- Hahn-Strömberg, Victoria, 1971-, et al.
(författare)
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Polymorphisms in the CLDN1 and CLDN7 genes are related to differentiation and tumor stage in colon carcinoma
- 2014
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley-Blackwell. - 0903-4641 .- 1600-0463. ; 122:7, s. 636-642
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Tidskriftsartikel (refereegranskat)abstract
- Tight junction is composed of transmembrane proteins important for maintaining cell polarity and regulating ion flow. Among these proteins are the tissue-specific claudins, proteins that have recently been suggested as tumor markers for several different types of cancer. An altered claudin expression has been observed in colon, prostatic, ovarian, and breast carcinoma. The aim of this study was to analyze the allele frequencies of three common single nucleotide polymorphisms (SNPs) in the genes for claudin 1 and claudin 7 in colon cancer (CC) patients and in a control population of healthy blood donors. Pyrosequencing was used to genotype the CLDN1 SNP rs9869263 (c.369C>T), and the CLDN7 SNPs rs4562 (c.590C>T) and rs374400 (c.606T>G) in DNA from 102 formalin fixed paraffin embedded (FFPE) colon cancer tissue, and 111 blood leukocyte DNA from blood/plasma donors. These results were correlated with clinical parameters such as TNM stage, tumor localization, tumor differentiation, complexity index, sex, and age. We found that there was a significant association between the CLDN1 genotype CC in tumor samples and a higher risk of colon cancer development (OR 3.0, p < 0.001). We also found that the CLDN7 rs4562 (c.590C>T) genotype CT had a higher risk of lymph node involvement (p = 0.031) and a lower degree of tumor differentiation (p = 0.028). In the control population, the allele frequencies were very similar to those in the HapMap cohort for CLDN7. The CLDN1 rs9869263 genotype (c.369C>T) was related to increased risk of colon cancer, and the CLDN7 rs4562 genotype (c.590C>T) was related to tumor differentiation and lymph node involvement in colon carcinoma. Further studies are warranted to ascertain their potential uses as biomarkers predicting tumor development, proliferation, and outcome in this disease.
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| 4. |
- Jonsson, Lina, 1982, et al.
(författare)
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Association between ASMT and autistic-like traits in children from a Swedish nationwide cohort
- 2014
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Ingår i: Psychiatric Genetics. - Stockholm : Lippincott Williams & Wilkins. - 0955-8829 .- 1473-5873. ; 24:1, s. 21-27
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Tidskriftsartikel (refereegranskat)abstract
- Individuals with autism spectrum disorders often show low levels of melatonin, and it has been suggested that this decrease may be because of the low activity of the acetylserotonin O-methyltransferase (ASMT), the last enzyme in the melatonin-synthesis pathway. Also, genetic variants in ASMT have been associated with autism, as well as with low ASMT activity and melatonin levels, suggesting that the low ASMT activity observed in autism may partly be because of variations within the ASMT gene. In this study, we present a symptom-based approach to investigate possible associations between ASMT and autistic-like traits in the general population. To this end, continuous measures of autistic-like traits were assessed in a nationally representative twin cohort (n=1771) from Sweden and six single nucleotide polymorphisms (SNPs), and a duplication of exons 2-8 in ASMT were genotyped. Our results show a nominally significant association, in girls, between one single nucleotide polymorphism (rs5949028) in the last intron of ASMT and social interaction impairments. No significant association, however, was observed with traits related to language impairment or restricted and repetitive behavior. In conclusion, our results support the possible involvement of the ASMT gene in autism spectrum disorders, and our finding that only one of the three traits shows association suggests that genetic research may benefit from adopting a symptom-specific approach to identify genes involved in autism psychopathology.
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| 5. |
- Busi, Micol, 1975-, et al.
(författare)
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Navigating the Usher Syndrome Genetic Landscape : An Evaluation of the Associations between Specific Genes and Quality Categories of Cochlear Implant Outcomes
- 2024
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Ingår i: Audiology Research. - : MDPI. - 2039-4330 .- 2039-4349. ; 14:2, s. 254-263
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Forskningsöversikt (refereegranskat)abstract
- Usher syndrome (US) is a clinically and genetically heterogeneous disorder that involves three main features: sensorineural hearing loss, retinitis pigmentosa (RP), and vestibular impairment. With a prevalence of 4–17/100,000, it is the most common cause of deaf-blindness worldwide. Genetic research has provided crucial insights into the complexity of US. Among nine confirmed causative genes, MYO7A and USH2A are major players in US types 1 and 2, respectively, whereas CRLN1 is the sole confirmed gene associated with type 3. Variants in these genes also contribute to isolated forms of hearing loss and RP, indicating intersecting molecular pathways. While hearing loss can be adequately managed with hearing aids or cochlear implants (CIs), approved RP treatment modalities are lacking. Gene replacement and editing, antisense oligonucleotides, and small-molecule drugs hold promise for halting RP progression and restoring vision, enhancing patients’ quality of life. Massively parallel sequencing has identified gene variants (e.g., in PCDH15) that influence CI results. Accordingly, preoperative genetic examination appears valuable for predicting CI success. To explore genetic mutations in CI recipients and establish correlations between implant outcomes and involved genes, we comprehensively reviewed the literature to gather data covering a broad spectrum of CI outcomes across all known US-causative genes. Implant outcomes were categorized as excellent or very good, good, poor or fair, and very poor. Our review of 95 cochlear-implant patients with US, along with their CI outcomes, revealed the importance of presurgical genetic testing to elucidate potential challenges and provide tailored counseling to improve auditory outcomes. The multifaceted nature of US demands a comprehensive understanding and innovative interventions. Genetic insights drive therapeutic advancements, offering potential remedies for the retinal component of US. The synergy between genetics and therapeutics holds promise for individuals with US and may enhance their sensory experiences through customized interventions.
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| 6. |
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| 7. |
- Risal, Sanjiv, et al.
(författare)
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Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome
- 2019
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Ingår i: Nature Medicine. - : Nature Publishing Group. - 1078-8956 .- 1546-170X. ; 25:12, s. 1894-1904
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Tidskriftsartikel (refereegranskat)abstract
- How obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring is unclear. In a Swedish nationwide register-based cohort and a clinical case-control study from Chile, we found that daughters of mothers with PCOS were more likely to be diagnosed with PCOS. Furthermore, female mice (F0) with PCOS-like traits induced by late-gestation injection of dihydrotestosterone, with and without obesity, produced female F1-F3 offspring with PCOS-like reproductive and metabolic phenotypes. Sequencing of single metaphase II oocytes from F1-F3 offspring revealed common and unique altered gene expression across all generations. Notably, four genes were also differentially expressed in serum samples from daughters in the case-control study and unrelated women with PCOS. Our findings provide evidence of transgenerational effects in female offspring of mothers with PCOS and identify possible candidate genes for the prediction of a PCOS phenotype in future generations.
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| 8. |
- Karypidis, A.-H., et al.
(författare)
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Deletion polymorphism of the UGT2B17 gene is associated with increased risk for prostate cancer and correlated to gene expression in the prostate
- 2008
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Ingår i: The Pharmacogenomics Journal. - Avenet, NJ : Nature Pub. Group. - 1470-269X .- 1473-1150. ; 8:2, s. 147-151
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Tidskriftsartikel (refereegranskat)abstract
- Metabolism of androgens includes glucuronidation, the major pathway of steroid elimination in several steroid target tissues. Glucuronidation is catalysed by UDP-glucuronosyltransferases (UGTs). UGT2B17 has been shown to be particularly active against androgens and is highly abundant in the prostate. Recently, we discovered that deletion of the UGT2B17 gene is associated with low or undetectable urinary testosterone levels. Here, we determined the phenotypic outcome of the deletion by quantifying the UGT2B17 mRNA expression in normal prostate tissues in individuals with different genotypes. Additionally, the frequency of UGT2B17 deletion polymorphism was studied in a Swedish population-based case–control study including 176 patients diagnosed with prostate cancer and 161 controls. We found that the individuals homozygous for the insertion allele expressed 30 times more UGT2B17 mRNA in prostate tissue than the heterozygotes. Carriers of the deletion allele had a significantly increased risk of prostate cancer (OR=2.07; 95% CI=1.32–3.25). In conclusion, these results show the UGT2B17 deletion polymorphism is associated with prostate cancer risk.
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| 9. |
- Bereketoglu, Ceyhun, et al.
(författare)
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The brominated flame retardants TBECH and DPTE alter prostate growth, histology and gene expression patterns in the mouse
- 2021
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Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 102, s. 43-55
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Tidskriftsartikel (refereegranskat)abstract
- The brominated flame retardants (BFRs), 1,2-dibromo-4-(1,2 dibromoethyl)cyclohexane (TBECH) and 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE) bind to the androgen receptor (AR). In vitro bioassays have shown that TBECH is a potent androgen agonist while DPTE is a potent AR antagonist. Both TBECH and DPTE alter gene expression associated with AR regulation. However, it remains to be determined if TBECH and DPTE can affect the prostate. For this reason, we exposed CD1 mice to a 1:1 mixture of TBECH diastereomers α and β, a 1:1 mixture of γ and δ, and to DPTE, and tested their effects on prostate growth, histology and gene expression profiles. Castrated (C) mice were used to study the androgenic effects of TBECHαβ and TBECHγδ while the antagonistic effects of DPTE were studied in non-castrated (NC) mice. We observed that testosterone and TBECHγδ increased body and prostate weights while TBECHαβ affected neither of them; and that DPTE had no effect on body weight but reduced prostate weight drastically. Histomorphometric analysis of the prostate revealed epithelial and glandular alterations in the TBECHγδ group comparable to those in testosterone group while alterations in the TBECHαβ group were less pronounced. DPTE displayed androgen antagonist activity reminiscent of castration. The transcription profile of the prostate was altered by castration and exposure to testosterone and to TBECHγδ reversed several of these changes. Testosterone and TBECHγδ also regulated the expression of several androgen responsive genes implicated in prostate growth and cancer. While DPTE resulted in a drastic reduction in prostate weight, it only affected a small number of genes. The results indicate that TBECHγδ and DPTE are of high human health concern as they may contribute to changes in prostate growth, histology and function.
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| 10. |
- Kaminsky, Zachary A., et al.
(författare)
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DNA methylation profiles in monozygotic and dizygotic twins
- 2009
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 41:2, s. 240-245
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Tidskriftsartikel (refereegranskat)abstract
- Twin studies have provided the basis for genetic and epidemiological studies in human complex traits. As epigenetic factors can contribute to phenotypic outcomes, we conducted a DNA methylation analysis in white blood cells (WBC), buccal epithelial cells and gut biopsies of 114 monozygotic (MZ) twins as well as WBC and buccal epithelial cells of 80 dizygotic (DZ) twins using 12K CpG island microarrays. Here we provide the first annotation of epigenetic metastability of approximately 6,000 unique genomic regions in MZ twins. An intraclass correlation (ICC)-based comparison of matched MZ and DZ twins showed significantly higher epigenetic difference in buccal cells of DZ co-twins (P = 1.2 x 10(-294)). Although such higher epigenetic discordance in DZ twins can result from DNA sequence differences, our in silico SNP analyses and animal studies favor the hypothesis that it is due to epigenomic differences in the zygotes, suggesting that molecular mechanisms of heritability may not be limited to DNA sequence differences.
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