NOS3 gene Glu298Asp polymorphism and severity of disease in patients of ADPKD from North India

Abstract

IntroductionGenetic modifying factors play a significant role in disease progression in autosomal dominant polycystic kidney disease (ADPKD). Identification of these factors could inform about targets for intervention. The present study investigates the role of Glu298Asp (c.894G>T) polymorphism of NOS3 gene in the progression of disease in ADPKD patients from North India, and compares with the results in studies among other ethnic groups. MethodsGenotyping for c.894G>T polymorphism was carried out in 123 patients of ADPKD and 100 healthy controls using polymerase chain reaction method. The allelic and genotypic frequencies of patients of ADPKD and healthy controls were analyzed using Chi-Square test. The mean age at onset of ESRD in the patients with PKD1 gene mutations, and in those with hypertension was correlated with G and T alleles of this polymorphism using Student's t-test. ResultsDistribution of GG, GT and TT genotypes were 0.73, 0.25 and 0.02 in patients of ADPKD and 0.67, 0.31 and 0.02 in healthy controls, respectively. The differences in the genotype frequencies between patients and controls were not significant (p=0.604). The frequency of mutant allele T of c.894G>T polymorphism did not vary significantly among patients of ADPKD with ESRD and those without ESRD (p=0.112). This polymorphism was also not associated with hypertension (p=0.681) and severity of disease in PKD1-linked patients (p=0.582). ConclusionsThe GT/TT genotype of c.894G>T (Glu298Asp) polymorphism did not have a significant role in modifying the progression of the disease in patients of ADPKD, or those with mutations in PKD1 gene from North India.