Association of the PPARGC1A gene polymorphism with diabetic nephropathy in an Asian Indian population (CURES-41).
BACKGROUND
The aim of this study was to evaluate the association of polymorphisms of the peroxisome proliferator-activated receptor gamma (PPARG) gene and peroxisome proliferators-activated receptor gamma co-activator 1 alpha (PPARGC1A) gene with diabetic nephropathy (DN) in Asian Indians.


METHODS
Six common polymorphisms, 3 of the PPARG gene [-1279G/A, Pro12Ala, and His478His (C/T)] and 3 of the PPARGC1A gene (Thr394Thr, Gly482Ser, and +A2962G) were studied in 571 normal glucose-tolerant (NGT) subjects, 255 type 2 diabetic (T2D) subjects without nephropathy, and 141 DN subjects. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Logistic regression analysis was performed to assess the covariables associated with DN.


RESULTS
Among the 6 polymorphisms examined, only the Gly482Ser of the PPARGC1A gene was significantly associated with DN. The genotype frequency of Ser/Ser genotype of the PPARGC1A gene was 8.8% (50/571) in NGT subjects, 7.8% (20/255) in T2D subjects, and 29.8% (42/141) in DN subjects. The odds ratios (ORs) for DN for the susceptible Gly/Ser and Ser/Ser genotype after adjusting for age, sex, body mass index, and duration of diabetes were 2.14 [95% confidence interval (CI), 1.23-3.72; P = 0.007] and 8.01 (95% CI, 3.89-16.47; P < 0.001), respectively. The unadjusted OR for DN for the XA genotype of the Thr394Thr polymorphism was 1.87 (95% CI, 1.20-2.92; P = 0.006) compared to T2D subjects. However, the significance was lost (P = 0.061) when adjusted for age, sex, BMI, and duration of diabetes. The +A2962G of PPARGC1A and the 3 polymorphisms of PPARG were not associated with DN.


CONCLUSIONS
The Gly482Ser polymorphism of the PPARGC1A gene is associated with DN in Asian Indians.
Gayathri
Sakthi Baby
SB
Madras Diabetes Research Foundation, and Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Noncommunicable Diseases Prevention Control, Gopalapuram, Chennai, India.
Radha
Venkatesan
V
Vimaleswaran
Karani S
KS
Mohan
Viswanathan
V
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D044466:Asian People / Q000235:genetics; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*
D006360:Heat-Shock Proteins; D047495:PPAR gamma; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors