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

Authors

Michael Traurig
Robert L. Hanson
Alejandra Marinelarena
Sayuko Kobes
Paolo Piaggi
Shelley A. Cole
Joanne E. Curran, The University of Texas Rio Grande Valley
John Blangero, The University of Texas Rio Grande Valley
Harald H. H. Goring, The University of Texas Rio Grande Valley
Satish Kumar, The University of Texas Rio Grande Valley

Document Type

Article

Publication Date

2-2016

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.

Comments

© 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. Original published version available at https://doi.org/10.2337/db15-0571

Recommended Citation

Traurig, M., Hanson, R. L., Marinelarena, A., Kobes, S., Piaggi, P., Cole, S., Curran, J. E., Blangero, J., Göring, H., Kumar, S., Nelson, R. G., Howard, B. V., Knowler, W. C., Baier, L. J., & Bogardus, C. (2016). Analysis of SLC16A11 Variants in 12,811 American Indians: Genotype-Obesity Interaction for Type 2 Diabetes and an Association With RNASEK Expression. Diabetes, 65(2), 510–519. https://doi.org/10.2337/db15-0571

Publication Title

Diabetes

DOI

10.2337/db15-0571

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics