Autosomal Dominant Polycystic Kidney Disease (ADPKD) accounts for 2.6% of the

patients with Chronic Kidney Disease in India. The disease is caused by pathogenic

sequence variants in either PKD1 or PKD2 gene. The primary aim of the present

study was to evaluate PKD1 and PKD2 genes to identify the disease causing variants

in patients of ADPKD. A significant phenotypic variability is observed in patients of

ADPKD with respect to progression of the disease. Genetic modifying factors are

reported to be associated with this variability and thus, identification of these factors

could inform about targets for intervention. Given this, an attempt was made to

investigate the role of Glu298Asp (c.894G>T) polymorphism of NOS3 gene and two

promoter polymorphisms (-2578C>A and -1154G>A) of VEGF gene in progression

of disease in ADPKD patients.

PKD1 and PKD2 variants were analyzed by direct gene sequencing and/or multiplex

ligation-dependent probe amplification (MLPA) in 125 unrelated patients of ADPKD.

The pathogenic potential of the variants was evaluated computationally using multiple

in silico web based prediction tools and by segregation analysis. NOS3 and VEGF

gene polymorphisms were genotyped in 123 patients of ADPKD and 100 healthy

controls. Genotyping was carried out using the amplification refractory mutationspecific

polymerase chain reaction (ARMS-PCR) for NOS3 and restriction fragment

length polymorphism (RFLP) for VEGF gene polymorphisms. Comparison of allele,

genotype and haplotype frequencies between groups was done by using Chi-Square

(χ2) test or Fisher's exact test.