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- Assimes, Themistocles L., et al.
(författare)
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Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies
- 2010
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 56:19, s. 1552-1563
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Tidskriftsartikel (refereegranskat)abstract
- Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of >= 2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study. (J Am Coll Cardiol 2010;56:1552-63) (C) 2010 by the American College of Cardiology Foundation
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| 3. |
- Nettleton, Jennifer A., et al.
(författare)
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Interactions of Dietary Whole-Grain Intake With Fasting Glucose- and Insulin-Related Genetic Loci in Individuals of European Descent A meta-analysis of 14 cohort studies
- 2010
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Ingår i: Diabetes Care. - 1935-5548. ; 33:12, s. 2684-2691
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - Whole-grain foods are touted for multiple health benefits including enhancing insulin sensitivity and reducing type 2 diabetes risk Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin RESEARCH DESIGN AND METHODS - Via meta-analysis of data from 14 cohorts comprising similar to 48 000 participants of European descent we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations For tests of interaction we considered a P value <0 0028 (0 05 of 18 tests) as statistically significant RESULTS - Greater whole grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics other dietary and lifestyle factors, and BMI (beta [95% Cl] per 1-serving greater whole grain intake -0 009 mmol/l glucose [-0 013 to -0 0051 P < 0 0001 and -0011 pmol/l [In] insulin [-0 015 to -0 0071 P = 0 0003) No interactions met our multiple testing adjusted statistical significance threshold The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0 006) where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin raising allele
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