TMPRSS6 gene polymorphisms, body iron stores and risk of type 2 diabetes mellitus in a Chinese population

Abstract

Several studies have shown that iron overload (i.e., elevated body iron stores) is involved in the pathogenesis of type 2 diabetes mellitus (T2DM). rs4820268 and rs855791, single nucleotide polymorphisms (SNPs) in the transmembrane protease serine 6 gene (TMPRSS6), were strongly associated with serum iron concentrations in recent genome-wide association scans. However, whether rs4820268 and rs855791 are associated with risk of T2DM remains unknown. To determine the association between these variants and risk of T2DM, we conducted a case-control study of 688 cases of T2DM and 983 healthy controls in a Chinese population. In addition, we also explored the association between these variants and plasma ferritin concentrations in a subset of subjects who participated in the ferritin test. The frequency of rs4820268 G allele was 0.528 in controls and 0.516 in T2DM patients. As for rs855791 A allele, the frequency was 0.552 and 0.524, respectively. We found that neither rs4820268 nor rs855791 showed significant association with risk of T2DM. For rs4820268, the odds ratio (OR) for T2DM among persons with GG genotype, compared to those with AA genotype, was 0.939 (95% confidence interval (CI) 0.690-1.279) after adjustment for age, sex and body mass index. For rs855791, after multivariate adjusted, the OR for T2DM among people with AA genotype, compared to those with GG genotype, was 0.846 (95% CI 0.621-1.153). On the other hand, in our study, no significant associations were observed between the above variants and plasma ferritin concentrations. For rs4820268, the geometric means of ferritin were 130.52 ng/mL, 133.62 ng/mL and 132.30 ng/mL in persons carried AA, AG and GG genotypes (P > 0.05). For rs855791, the geometric means of ferritin were 134.39 ng/mL, 135.64 ng/mL and 126.14 ng/mL in persons carried GG, AG and AA genotypes (P > 0.05). In conclusion, our data indicate that rs4820268 and rs855791 in TMPRSS6 gene may not be associated with risk of T2DM or elevated body iron stores.