Analysis of SLC16A11 variants in 12,811 American Indians: Genotype-obesity interaction for type 2 diabetes and an association with RNASEK expression

Michael Traurig, Robert L. Hanson, Alejandra Marinelarena, Sayuko Kobes, Paolo Piaggi, Shelley Cole, Joanne E. Curran, John Blangero, Harald Göring, Satish Kumar, Robert G. Nelson, Barbara V. Howard, William C. Knowler, Leslie J. Baier, Clifton Bogardus

    Research output: Contribution to journalArticlepeer-review

    10 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)510-519
    Number of pages10
    JournalDiabetes
    Volume65
    Issue number2
    DOIs
    StatePublished - Feb 2016

    ASJC Scopus subject areas

    • Internal Medicine
    • Endocrinology, Diabetes and Metabolism

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