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Diabetes. 2016 Feb;65(2):510-9. doi: 10.2337/db15-0571. Epub 2015 Oct 20.

Analysis of SLC16A11 Variants in 12,811 American Indians: Genotype-Obesity Interaction for Type 2 Diabetes and an Association With RNASEK Expression.

Author information

1
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ.
2
Texas Biomedical Research Institute, San Antonio, TX.
3
South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley School of Medicine, Brownsville, TX.
4
MedStar Health Research Institute, Hyattsville, MD Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC.
5
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ cbogardu@mail.nih.gov.

Abstract

Genetic variants in SLC16A11 were recently reported to be associated with type 2 diabetes in Mexican and other Latin American populations. The diabetes risk haplotype had a frequency of 50% in Native Americans from Mexico but was rare in Europeans and Africans. In the current study, we analyzed SLC16A11 in 12,811 North American Indians and found that the diabetes risk haplotype, tagged by the rs75493593 A allele, was nominally associated with type 2 diabetes (P = 0.001, odds ratio 1.11). However, there was a strong interaction with BMI (P = 5.1 × 10(-7)) such that the diabetes association was stronger in leaner individuals. rs75493593 was also strongly associated with BMI in individuals with type 2 diabetes (P = 3.4 × 10(-15)) but not in individuals without diabetes (P = 0.77). Longitudinal analyses suggest that this is due, in part, to an association of the A allele with greater weight loss following diabetes onset (P = 0.02). Analyses of global gene expression data from adipose tissue, skeletal muscle, and whole blood provide evidence that rs75493593 is associated with expression of the nearby RNASEK gene, suggesting that RNASEK expression may mediate the effect of genotype on diabetes.

PMID:
26487785
PMCID:
PMC4747458
DOI:
10.2337/db15-0571
[Indexed for MEDLINE]
Free PMC Article

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