Genetic analysis of the NAT2 and CYP2D6 polymorphisms in white patients with non-insulin-dependent diabetes mellitus.

The arylamine N-acetyltransferase (NAT2) polymorphism has been related to the risk of developing non-insulin-dependent diabetes mellitus (NIDDM). Several studies suggested an excess of rapid acetylators among NIDDM patients. This may be explained by an increased risk to develop NIDDM among subjects with the rapid acetylator capacity, or by changes in the acetylator status due to the disease or drug therapy. In order to elucidate this controversial topic, we have studied by a mutation-specific polymerase chain amplification (PCR) method the occurrence of seven point mutations at the coding region of the NAT2 gene in genomic DNA from 111 patients with NIDDM and 217 healthy controls. In addition, we have studied by the combined use of PCR and restriction fragment length polymorphism the occurrence of seven allelic variants of the CYP2D6 gene in the same subjects. In contrast to previous phenotyping studies, no relationship was found between NAT2 polymorphism and NIDDM or its complications such as nephropathy or neuropathy. The CYP2D6 genotype was similar between cases and controls. Our findings do not provide a genetic basis for any association of NIDDM and NAT2 polymorphism, suggesting that any excess of subjects with the rapid acetylator phenotype among patients with NIDDM should be secondary to the disease or concomitant drug therapy.