Association Analysis of Variation in/Near FTO, CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, LOC387761, and CDKN2B With Type 2 Diabetes and Related Quantitative Traits in Pima Indians

被引：154

作者：

Rong, Rong ^{[1
]}

Hanson, Robert L. ^{[1
]}

Ortiz, Daniel ^{[1
]}

Wiedrich, Christopher ^{[1
]}

Kobes, Sayuko ^{[1
]}

Knowler, William C. ^{[1
]}

Bogardus, Clifton ^{[1
]}

Baier, Leslie J. ^{[1
]}

机构：

[1] NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA

来源：

DIABETES | 2009年 / 58卷 / 02期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; FAT MASS; GENETIC-VARIANTS; RISK LOCI; OBESITY; POLYMORPHISMS; REPLICATION; CHILDHOOD; TCF7L2; TISSUE;

D O I：

10.2337/db08-0877

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

OBJECTIVE-In recent genome-wide association studies, variants in CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, CDKN2B, LOC387761, and FTO were associated with risk for type 2 diabetes in Caucasians. We investigated the association of these single nucleotide polymorphisms (SNPs) and some additional tag SNPs with type 2 diabetes and related quantitative traits in Pima Indians. RESEARCH DESIGN AND METHODS-Forty-seven SNPs were genotyped in 3,501 Pima Indians informative for type 2 diabetes and BMI, among whom 370 had measures of quantitative traits. RESULTS-FTO provided the strongest evidence for replication, where SNPs were associated with type 2 diabetes (odds ratio = 1.20 per copy of the risk allele, P = 0.03) and BMI (P = 0.002). None of tire other previously reported SNPs were associated with type 2 diabetes; however, associations were found between CDKAL1 and HHEX variants and acute insulin response (AIR), where the Caucasian risk alleles for type 2 diabetes were associated with reduced insulin secretion in normoglycemic Pima, Indians. Multiallelic analyses of carrying risk alleles for multiple genes showed correlations between number of risk alleles and type 2 diabetes and impaired insulin secretion in normoglycemic subjects (P = 0.006 and 0.0001 for type 2 diabetes and AIR, respectively), supporting the hypothesis that many of these genes influence diabetes risk by affecting insulin secretion. CONCLUSIONS-Variation in FTO impacts BMI, but the implicated common variants in the other genes did not confer a significant risk for type 2 diabetes in Pima Indians. However, confidence intervals for their estimated effects were consistent with the small effects reported in Caucasians, and the multiallelic "genetic risk profile" identified in Caucasians is associated with diminished early insulin secretion in Pima Indians. Diabetes 58: 478-488, 2009

引用

页码：478 / 488

页数：11

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