Peroxisome proliferator-activated receptor-gamma gene polymorphism and risk of cardiovascular disease in patients with diabetic nephropathy.
BACKGROUND
Peroxisome proliferator-activator receptor-gamma (PPAR-gamma) is a nuclear receptor that serves important roles in intermediate metabolism. We examined the relationship between two PPAR-gamma gene polymorphisms, namely the P12A and C161T, and cardiovascular disease in patients with diabetic nephropathy.


METHODS
We studied 170 predialysis and 50 peritoneal dialysis patients with diabetic nephropathy. The PPAR-gamma genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism assay. The patients were then followed prospectively for the development of cardiovascular events. Cardiovascular mortality and all-cause mortality were also compared.


RESULTS
There were 91 male cases. The mean age was 64.3 +/- 10.6 years. The frequencies of Pro/Pro and Pro/Ala genotypes of the P12A polymorphism were 95 and 5%, respectively; CC, CT and TT genotypes of the C161T polymorphism were 55.5, 39.5 and 5.0%, respectively. For the P12A polymorphism, the event-free survival was 56.5 and 9.1% at 60 months for Pro/Pro and Pro/Ala genotypes, respectively (p = 0.0005). For the C161T polymorphism, the event-free survival was 61.5 and 44.9% for CC and CT/TT genotypes, respectively (p = 0.0044). By multivariate analysis with the Cox proportional hazard model to adjust for confounders, the independent factors for event-free survival were P12A and C161T polymorphisms, age and diastolic blood pressure. In this model, the Pro/Ala genotype conferred 7.6-fold (95% CI 2.1- to 28.0-fold, p = 0.002) excess hazard of developing primary cardiovascular end point as compared to the Pro/Pro genotype, while each T allele at the 161 position conferred 83.4% (95% CI 15.2-291.9%, p = 0.011) excess hazard.


CONCLUSIONS
We conclude that P12A and C161T polymorphisms of the PPAR-gamma gene are important predictors of cardiovascular event in patients with diabetic nephropathy. Further studies are needed to examine the interaction of PPAR-gamma gene polymorphisms and thiazolidinedione treatment on the cardiovascular risk in this group of patients.
Szeto
Cheuk-Chun
CC
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, China. ccszeto@cuhk.edu.hk
Chow
Kai-Ming
KM
Poon
Peter Yam-Kau
PY
Kwan
Bonnie Ching-Ha
BC
Li
Philip Kam-Tao
PK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000235:genetics / Q000401:mortality; D003928:Diabetic Nephropathies / Q000150:complications*; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies
D047495:PPAR gamma