Metabolomics study on the association between nicotinamide N-methyltransferase gene polymorphisms and type 2 diabetes

Numerous reports have demonstrated that activities of nicotinamide N-methyltransferase (NNMT) are significantly associated with type 2 diabetes (T2D), and more than 200 single nucleotide polymorphisms (SNPs) have been identified across NNMT gene to date. Although two SNPs (rs694539 and rs1941404) have been found significantly associated with a variety of noninfectious chronic diseases, the association between NNMT gene polymorphisms and T2D has not been reported yet. In this paper, 558 T2D patients and 442 healthy controls were recruited from Chinese Han population. After a case-control study on the association between the two SNPs (rs694539 and rs1941404) and T2D, we found that the rs1941404 is significantly associated with T2D and the CC carriers at this locus are T2D susceptible population. The following metabolomics study showed that the rs1941404 variation is able to affect the metabolic pathways of tryptophan, tyrosine, and arginine, which may partly explain why the rs1941404 variation is significantly associated with T2D.