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 (NI DDM). Several studies suggested an excess of rapid acetylators among N IDDM patients. This may be explained by an increased risk to develop N IDDM 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-s pecific 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 additio n, we have studied by the combined use of PCR and restriction fragment length polymorphism the occurrence of seven allelic variants of the C YP2D6 gene in the same subjects. In contrast to previous phenotyping s tudies, no relationship was found between NAT2 polymorphism and NIDDM or its complications such as nephropathy or neuropathy, The CYP2D6 gen otype was similar between cases and controls, Our findings do not prov ide a genetic basis for any association of NIDDM and NAT2 polymorphism , suggesting that any excess of subjects with the rapid acetylator phe notype among patients with NIDDM should be secondary to the disease or concomitant drug therapy.