title: Association of myeloperoxidase G-463A gene polymorphism with diabetic nephropathy in Japanese type 2 diabetic subjects.
abstract: It is possible that myeloperoxidase (MPO) contributes to the pathogenesis of diabetic nephropathy through the production of reactive oxygen species and HOCl/OCl⁻. In this study, we examined the relationship between renal damage and MPO G-463A gene polymorphism that is associated with its transcription activity in diabetic patients. We evaluated the association between MPO G-463A polymorphism and the prevalence of proteinuria and estimated GFR (eGFR) in 1448 Japanese type 2 diabetic subjects. The prevalence of macroalbuminuria was higher as the number of G alleles increased (GG (7.6%), GA (3.8%), AA (0.0%), p for trend=0.0269). The number of G alleles was significantly associated with macroalbuminuria (odds ratio 2.12, 95%CI 1.06-4.24, p=0.0344) even after adjustment for conventional risk factors. Inversely, eGFR was lower as the number of G alleles increased (GG (76.7±20.7 mL/min/1.73m²), GA (81.0±22.8 mL/min/1.73m²), AA (92.0±23.1 mL/min/1.73m²), p for trend=0.0025) and the number of G allele was an independent risk factor for a low eGFR (β=-0.072, p=0.003). We also examined the association between MPO expression and several stages of renal damage in a high-fat diet-induced diabetic mouse model. The proteinuria-induced increase in MPO expression was markedly enhanced in diabetic mice, and MPO expression was significantly correlated with the severity of kidney damage. In conclusion, it is likely that the G allele of the MPO G-476T polymorphism is a susceptibility allele for renal injury in type 2 diabetic patients.
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita 565-0871, Japan. katakami@endmet.med.osaka-u.ac.jp
authors.forename: Naoto
authors.initials: N
authors.lastname: Katakami
authors.forename: Shinji
authors.initials: S
authors.lastname: Kume
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.forename: Takashi
authors.initials: T
authors.lastname: Uzu
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D024509:3' Flanking Region; D000368:Aged; D000419:Albuminuria / Q000453:epidemiology / Q000209:etiology; D000818:Animals; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009195:Peroxidase / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012720:Severity of Illness Index
chemical_list: D009195:Peroxidase