Contribution of SLC30A8 variants to the risk of type 2 diabetes in a multi-ethnic population: a case control study

BACKGROUND: Several studies have shown the association of solute carrier family 30 (zinc transporter) member 8 (SLC30A8) rs13266634 with type 2 diabetes (T2D). However, the association of alternative variants and haplotypes of SLC30A8 with T2D have not been studied in different populations. The aim of this study is to assess the association of the alternative SLC30A8 variants, rs7002176 and rs1995222 as well as the most common variant, rs13266634 and haplotypes with glutamic acid decarboxylase antibodies (GADA) negative diabetes in Malaysian subjects. METHODS: Single nucleotide polymorphisms (SNPs) of SLC30A8; rs7002176, rs1995222 and rs13266634 were genotyped in 1140 T2D and 973 non-diabetic control subjects. Of these, 33 GADA positive diabetic subjects and 353 metabolic syndrome (MetS) subjects were excluded from subsequent analysis. RESULTS: The recessive genetic model controlled for age, race, gender and BMI shows that the alternative SLC30A8 variant, rs1995222 is associated with GADA negative diabetes (OR = 1.29, P = 0.02) in Malaysian subjects. The most common variant, rs13266634 is also associated with GADA negative diabetes (OR = 1.45, P = 0.001). This association is more pronounced among Malaysian Indians (OR = 1.93, P = 0.001). Moreover, the CG haplotype and CG-CG diplotype have been equally associated with increased diabetic risk (OR = 1.67, P = 8.6 × 10(-5)). CONCLUSIONS: SLC30A8 SNPs and haplotypes are associated with GADA negative diabetes in Malaysian subjects, and this association is markedly higher among Malaysian Indian subjects.