The N-acetyltransferase (NAT) gene: an early risk marker for diabetic nephropathy in Japanese type 2 diabetic patients?
A point mutation in the N-acetyltransferase gene (NAT2) leads to the recessive trait for the slow acetylator phenotype, which is suggested to be associated with microalbuminuria in Type 1 diabetic patients. Our study was designed to elucidate whether the NAT2 gene polymorphism would be a marker for diabetic nephropathy. The genotype distribution was studied in Japanese Type 2 diabetic patients with established nephropathy (n = 43), with microalbuminuria (n = 24), with normoalbuminuria (n = 18), non-diabetic patients with kidney disease (n = 62), and healthy control subjects (n = 51). The different alleles of the NAT2 gene were identified by restriction fragment length polymorphism analysis: the gene was amplified from genomic DNA (obtained from blood) and digested with restriction enzymes. The genotype was classified by the specific pattern of each allele (M1, M2, M3) in the agarose electrophoresis and ethdium bromide fluorescence. Alleles M1, M2, and M3 of NAT2 gene were found in 42.4% of all subjects (40.0% in all diabetic patients and 44.2% in all non-diabetic controls). The prevalence of the genotype, encoding the slow acetylator phenotype, was 7.0% in diabetic patients with established diabetic nephropathy, 20.8% in microalbuminuric diabetic patients, 0% in normoalbuminuric diabetic patients, 6.5% in non-diabetic patients with kidney disease, and 7.8% in healthy control subjects. The differences in the prevalence were non-significant. The results suggest that the N-acetyltransferase gene polymorphism may not be a genetic risk marker for diabetic nephropathy in Japanese Type 2 diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical Research Institute, International Medical Centre of Japan, Tokyo.
S
S
Neugebauer
T
T
Baba
T
T
Watanabe
T
T
Ishizaki
K
K
Kurokawa
D000293:Adolescent; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000150:complications; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001483:Base Sequence; D004247:DNA / Q000032:analysis / Q000737:chemistry; D017931:DNA Primers / Q000737:chemistry; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D012307:Risk Factors
D017931:DNA Primers; D005819:Genetic Markers; D004247:DNA; D001191:Arylamine N-Acetyltransferase