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

MedStar author(s):
Citation: Diabetes. 65(2):510-9, 2016 Feb.PMID: 26487785Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., ExtramuralSubject headings: *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 AdultYear: 2016Local holdings: Available online from MWHC library: 1995 - present (after 6 months), Available in print through MWHC library: 1999 - 2006ISSN:
  • 0012-1797
Name of journal: DiabetesAbstract: 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.All authors: Baier LJ, Blangero J, Bogardus C, Cole S, Curran JE, Goring H, Hanson RL, Howard BV, Knowler WC, Kobes S, Kumar S, Marinelarena A, Nelson RG, Piaggi P, Traurig MFiscal year: FY2016Digital Object Identifier: Date added to catalog: 2016-06-13
Holdings
Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 26487785 Available 26487785

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.

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