Publikationsdatum:
2012-09-28
Beschreibung:
Insulin resistance (IR) is a key determinant of type 2 diabetes (T2D) and other metabolic disorders. This genome-wide association study (GWAS) was designed to shed light on the genetic basis of fasting insulin (FI) and IR in 927 non-diabetic African Americans. 5 396 838 single-nucleotide polymorphisms (SNPs) were tested for associations with FI or IR with adjustments for age, sex, body mass index, hypertension status and first two principal components. Genotyped SNPs ( n = 12) with P 〈 5 x 10 –6 in African Americans were carried forward for de novo genotyping in 570 non-diabetic West Africans. We replicated SNPs in or near SC4MOL and TCERG1L in West Africans. The meta-analysis of 1497 African Americans and West Africans yielded genome-wide significant associations for SNPs in the SC4MOL gene: rs17046216 ( P = 1.7 x 10 –8 and 2.9 x 10 –8 for FI and IR, respectively); and near the TCERG1L gene with rs7077836 as the top scoring ( P = 7.5 x 10 –9 and 4.9 x 10 –10 for FI and IR, respectively). In silico replication in the MAGIC study ( n = 37 037) showed weak but significant association (adjusted P -value of 0.0097) for rs34602777 in the MYO5A gene. In addition, we replicated previous GWAS findings for IR and FI in Europeans for GCKR , and for variants in four T2D loci ( FTO , IRS1 , KLF14 and PPARG ) which exert their action via IR. In summary, variants in/near SC4MOL , and TCERG1L were associated with FI and IR in this cohort of African Americans and were replicated in West Africans. SC4MOL is under-expressed in an animal model of T2D and plays a key role in lipid biosynthesis, with implications for the regulation of energy metabolism, obesity and dyslipidemia. TCERG1L is associated with plasma adiponectin, a key modulator of obesity, inflammation, IR and diabetes.
Print ISSN:
0964-6906
Digitale ISSN:
1460-2083
Thema:
Biologie
,
Medizin
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