| 1. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 2. |
- Hop, Paul J., et al.
(författare)
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Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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| 3. |
- Laux, Timothy S, et al.
(författare)
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Nicaragua revisited : evidence of lower prevalence of chronic kidney disease in a high-altitude, coffee-growing village
- 2012
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Ingår i: JN. Journal of Nephrology (Milano. 1992). - : SAGE Publications. - 1121-8428 .- 1724-6059. ; 25:4, s. 533-540
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic kidney disease (CKD) is found at epidemic levels in certain populations of the Pacific Coast in northwestern Nicaragua especially in younger men. There are knowledge gaps concerning CKD's prevalence in regions at higher altitudes.METHODS: A cross-sectional study of adults between the ages of 20 and 60 years in 1 coffee-growing village in Nicaragua located at 1,000 m above sea level (MASL) altitude was performed. Predictors included participant sex, age, occupation, conventional CKD risk factors and other factors associated with CKD suggested by previous surveys in Central America. Outcomes included serum creatinine (SCr) values >1.2 mg/dL for men and >0.9 mg/dL for women, estimated glomerular filtration rate (GFR) <60 ml/min per 1.73 m2, dipstick proteinuria stratified as microalbuminuria (30-300 mg/dL) and macroalbuminuria (>300 mg/dL), hypertension and body mass index.RESULTS: Of 324 eligible participants, 293 were interviewed (90.4%), and 267 of those received the physical exam (82.4% overall). Of the sample, 45% were men. Prevalence rate of estimated GFR <60 ml/min per 1.73 m2 was 0 for men (0%) and 2 for women (1.4%). The prevalence of at least microalbuminuria was significantly higher among men compared with women (27.5% vs. 21.4%, respectively; p=0.02).CONCLUSIONS: The CKD prevalence in this village is comparable to a previously studied Nicaraguan coffee-farming region and much lower than previously screened portions of northwestern Nicaragua. There is heterogeneity in CKD prevalence across Nicaragua. At this time, screenings should target individuals living in previously identified, higher risk regions. More work is needed to understand determinants of CKD in this resource-poor nation.
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| 4. |
- Laux, Timothy S., et al.
(författare)
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Revalence of hypertension and associated risk factors in six nicaraguan communities
- 2012
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Ingår i: Ethnicity & Disease. - 1049-510X. ; 22:2, s. 129-135
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Describe the prevalence of hypertension. Design: Population based cross-sectional survey. Setting: Six Nicaraguan communities with varying economies. Participants: 1,355 adults aged 20-60 years who completed both self-reported and quantitative measures of health. Main Outcome Measures: Prevalence of hypertension (systolic >= 140 mm Hg, diastolic >= 90 mm Hg, or self-reported medical history with diagnosis by a health care professional), uncontrolled hypertension (systolic >= 140 mm Hg or diastolic >= 90 mm Hg), diabetes (urinary glucose excretion >= 100 mg/dL or self-reported medical history diagnosed by a health care professional), and uncontrolled diabetes (urinary glucose excretion >= 100 mg/dL only). Results: The prevalence of hypertension was 22.0% (19.2% in men, 24.2% in women). Blood pressure was controlled in 31.0% of male hypertensives and 55.1% of female hypertensives (odds ratio [OR] 2.86; 95% confidence interval [CI] 1.74-4.69). Older age and higher body mass index were strongly associated with hypertension. Women who completed primary school had a lower risk of hypertension (OR .40; 95% CI .19-.85) compared to those with no formal education. A history of living in both urban and rural settings was associated with lower prevalence of hypertension (OR .52; 95% CI .34-.79). Diabetes mellitus was found in 1.2% of men and 4.3% of women. Male sex was independently associated with decreased risk of diabetes (OR .31; 95% CI .11-.86). Conclusions: At least one cardiovascular risk factor was found in half of this Nicaraguan sample. Cardiovascular risk factors should be the target of educational efforts, screening, and treatment.
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| 5. |
- Muthukumar, Kaliappan, et al.
(författare)
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Cerium Endohedral fullerenes (Ce@C82 and Ce2@C80) Theoretical Interpretations for Experimental observation
- 2008
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Konferensbidrag (refereegranskat)abstract
- Many questions remain unanswered for the endohedral fullerenes. Owing to the improvement in separation of isomers and in theoretical studies (DFT and ab-initio) evolving as imperative tool for characterization; these can be addressed.1;2 Understanding of the position and binding configuration of the metal atom inside the cage is crucial as it controls the structural and electronic properties of the molecule.3 Theoretical calculations proved to be efficient in explaining many controversies in the field of lanthanoid endohedral fullerenes.2-5 Fig; Ce2@C80; Ce2@C78) DFT optimized structures of Ce2@C80 D3d and Ce2@C78 D3h Here in this study we use DFT to characterize Ce doped metallofullerenes and report some surprising theoretical findings on the binding of cerium inside various carbon cages; (C60; C78; C80; C82). We observe that the presence of an additional Ce atom puts restrictions on the binding in the C80 cage6; but this does not happen in the C78 cage. We explain the reason behind this by analyzing the electronic structure. Further various spectra (RESPES; IETS; STM/STS) have been simulated for Ce@C82 and Ce2@C80 which we compare and discuss with experiments
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| 6. |
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| 7. |
- Muthukumar, Kaliappan, et al.
(författare)
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Surprising Findings for Ce Doped Fullerenes and Understanding of Experiments through Theoretical Modelling A DFT Approach
- 2008
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Endohedral fullerenes; which have one metal atom encapsulated; are relatively well studied compared to species that have two elements inside the cage.1-5 Cerium; the most reactive elements of the rare earth group can be encapsulated into fullerene (C78; C80; C82) cages;1 which works as a n-dopant and in the incarcerated form it can be used as quantum bits in quantum computing2. Understanding of the position and binding pattern of the metal atom inside the cage is important as it controls the structural and electronic properties of the molecule. We found that Ce in Ce@C82 has a specific and unique binding site in C82-C2v and has a C2v symmetric structure; which is explained by the specific charge pattern of this binding site and the symmetry of the MO s that comply well with the Ce d orbital bonding.6 This six-membered ring binding site is also favored by La in La@C82. Each of the six-membered rings of C80-Ih fulfills this symmetry criterion and therefore a similar kind of binding site is expected for Ce in Ce2@C80. But; we observe a novel binding site for Ce in presence of an additional cerium atom; while La preserve its usual binding pattern in La2@C80 as in La@C82.7 We here discuss and analyze the reason for the preference of novel binding site of Ce atoms in C80-Ih by explaining the competitive binding nature of Ce-Ce and Ce-C. Surprisingly; Ce in Ce2@C78 unlike Ce2@C80 has its binding pattern as in Ce@C60 and in Ce@C82 (binding to a six-membered ring). We explain this variation in binding together with the nature of the charge transfer between the Ce atoms and the cage (C82 and C80). In addition; we explain experimental observations for Ce@C82 and Ce2@C80 from RESPES; IETS; STM/STS spectra by comparison with simulated properties
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| 8. |
- Muthukumar, Kaliappan, et al.
(författare)
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Theoretical Predictions and Explanation of Experimental Observations for Ce Doped Fullerenes
- 2008
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Konferensbidrag (refereegranskat)abstract
- Fullerenes that have one metal atom encapsulated; for example M@C60; M@C70; M@C82; (M= Sc; Y; La; Ce; etc.) are relatively well studied compared to species that have two elements inside the cage.1-4 We recently reported the structure of Ce@C82 and explained the preferential binding site of Ce to only one of the thirty-one 6-membered rings of C82-C2v cage by identifying its specific charge pattern and the symmetry of the MO s that comply well with the Ce d orbital bonding.5 Since; each of the six-membered rings of C80-Ih fulfill the proposed criteria; similar kind of binding site is expected for Ce in Ce2@C80. But; we observe a novel binding site for Ce in presence of an additional cerium atom; while La in La2@C80 does bond with six-membered rings.6 In this study; we discuss and analyze the reason for the preference for a novel binding site by Ce atoms in C80-Ih through density functional calculations. Further; we explain the nature of the charge transfer between the Ce atoms and the cage (C82 and C80) and elucidate the oxidation state of Ce in these metallofullerenes by comparing the charge transfer in the conventional Ce tri halides (CeF3; CeBr3). In addition; we explain experimental observations for Ce@C82 and Ce2@C80 from RESPES; IETS; STM/STS spectra by comparison with simulated properties
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