Lack of Association betweenSLC30A8Variants and Type 2 Diabetes in Mexican American Families

Abstract

SLC30A8encodes zinc transporter 8 which is involved in packaging and release of insulin. Evidence for the association ofSLC30A8variants with type 2 diabetes (T2D) is inconclusive. We interrogated single nucleotide polymorphisms (SNPs) aroundSLC30A8for association with T2D in high-risk, pedigreed individuals from extended Mexican American families. This study of 118 SNPs within 50 kb of theSLC30A8locus tested the association with eight T2D-related traits at four levels: (i) each SNP using measured genotype approach (MGA); (ii) interaction of SNPs with age and sex; (iii) combinations of SNPs using Bayesian Quantitative Trait Nucleotide (BQTN) analyses; and (iv) entire gene locus using the gene burden test. Only one SNP (rs7817754) was significantly associated with incident T2D but a summary statistic based on all T2D-related traits identified 11 novel SNPs. Three SNPs and one SNP were weakly but interactively associated with age and sex, respectively. BQTN analyses could not demonstrate any informative combination of SNPs over MGA. Lastly, gene burden test results showed that at best theSLC30A8locus could account for only 1-2% of the variability in T2D-related traits. Our results indicate a lack of association of theSLC30A8SNPs with T2D in Mexican American families.