Analysis of SLC16A11 Variants in 12,811 American Indians: Genotype-Obesity Interaction for Type 2 Diabetes and an Association With RNASEK Expression.
Analysis of SLC16A11 Variants in 12,811 American Indians: Genotype-Obesity Interaction for Type 2 Diabetes and an Association With RNASEK Expression.
- 2016
Available online from MWHC library: 1995 - present (after 6 months), Available in print through MWHC library: 1999 - 2006
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 x 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 x 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. Copyright © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
English
0012-1797
*Diabetes Mellitus, Type 2/ge [Genetics]
*Endoribonucleases/me [Metabolism]
*Genetic Variation
*Indians, North American/ge [Genetics]
*Monocarboxylic Acid Transporters/ge [Genetics]
*Obesity/ge [Genetics]
Adolescent
Adult
Alleles
Arizona
Body Mass Index
Female
Genetic Predisposition to Disease
Haplotypes
Humans
Longitudinal Studies
Male
Middle Aged
North Dakota
Obesity/co [Complications]
Oklahoma
South Dakota
Weight Loss/ge [Genetics]
Young Adult
MedStar Health Research Institute
Journal Article
Research Support, N.I.H., Extramural
Available online from MWHC library: 1995 - present (after 6 months), Available in print through MWHC library: 1999 - 2006
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 x 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 x 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. Copyright © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
English
0012-1797
*Diabetes Mellitus, Type 2/ge [Genetics]
*Endoribonucleases/me [Metabolism]
*Genetic Variation
*Indians, North American/ge [Genetics]
*Monocarboxylic Acid Transporters/ge [Genetics]
*Obesity/ge [Genetics]
Adolescent
Adult
Alleles
Arizona
Body Mass Index
Female
Genetic Predisposition to Disease
Haplotypes
Humans
Longitudinal Studies
Male
Middle Aged
North Dakota
Obesity/co [Complications]
Oklahoma
South Dakota
Weight Loss/ge [Genetics]
Young Adult
MedStar Health Research Institute
Journal Article
Research Support, N.I.H., Extramural