Physiological Study on Association between Nicotinamide N-Methyltransferase Gene Polymorphisms and Hyperlipidemia

Abstract

Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide. Our previous works indicate that NNMT is involved in the body mass index and energy metabolism, and recently the association between a SNP (rs694539) of <i>NNMT</i> and a variety of cardiovascular diseases was reported. At present, more than 200 <i>NNMT</i> single nucleotide polymorphisms (SNPs) have been identified in the databases of the human genome projects; however, the association between rs694539 variation and hyperlipidemia has not been reported yet, and whether there are any SNPs in <i>NNMT</i> significantly associated with hyperlipidemia is still unclear. In this paper, we selected 19 SNPs in <i>NNMT</i> as the tagSNPs using Haploview software (Haploview 4.2) first and then performed a case-control study to observe the association between these tagSNPs and hyperlipidemia and finally applied physiological approaches to explore the possible mechanisms through which the <i>NNMT</i> polymorphism induces hyperlipidemia. The results show that a SNP (rs1941404) in <i>NNMT</i> is significantly associated with hyperlipidemia, and the influence of rs1941404 variation on the resting energy expenditure may be the possible mechanism for rs1941404 variation to induce hyperlipidemia.