Identification of PKD1 and PKD2 gene variants in a cohort of 125 Asian Indian patients of ADPKD.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) accounts for 2.6% of the patients with chronic kidney disease in India. ADPKD is caused by pathogenic variants in either PKD1 or PKD2 gene. There is no comprehensive genetic data from Indian subcontinent. We aimed to identify the pathogenic variants in the heterogeneous Indian population. PKD1 and PKD2 variants were identified 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 and were classified according to ACMG guidelines. Overall 300 variants were observed in PKD1 and PKD2 genes, of which 141 (47%) have been reported previously as benign. The remaining 159 variants were categorized into different classes based on their pathogenicity. Pathogenic variants were observed in 105 (84%) of 125 patients, of which 99 (94.3%) were linked to PKD1 gene and 6 (6.1%) to PKD2 gene. Of 159 variants, 97 were novel variants, of which 43 (44.33%) were pathogenic, and 10 (10.31%) were of uncertain significance. Our data demonstrate the diverse genotypic makeup of single gene disorders in India as compared to the West. These data would be valuable in counseling and further identification of probable donors among the relatives of patients with ADPKD.

Vascular Endothelial Growth Factor (VEGF) Gene Promoter Polymorphisms and Disease Progression in North Indian Cohort with Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a significant phenotypic variability in progression of the disease. Vascular endothelial growth factor (VEGF) has been reported to play a major role in renal pathophysiology. The aim of the present case-control study was to evaluate the association of two promoter polymorphisms (-2578C>A and-1154G>A) of VEGF gene and ADPKD. Genotyping was carried out in 123 ADPKD patients and 100 healthy controls, using a polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP). The genotype, allele and haplotype frequencies of these two polymorphisms in ADPKD patients were compared with those in controls, as well as in patients with early and advanced chronic kidney disease (CKD) stages, using Chi-square (χ2) test. The distribution frequency of CC, CA and AA genotypes of -2578C>A polymorphism differed significantly between patients and controls (0.31, 0.63 and 0.06 vs 0.37, 0.44 and 0.19, respectively (P=0.003)), but no significantly different genotype distribution was observed for the-1154G>A polymorphism. The A allele of -2578C>A and G allele of -1154G>A, were significantly more present in the controls as compared to the patients, and may provide protection for CKD under recessive (OR, 3.73; 95% CI, 1.45-9.62; P=0.0042), and dominant (OR, 0.55; 95%CI, 0.31-0.98; P=0.041) models. The [A;G] haplotype was more frequently present in controls (18%) than in cases (8%), (OR 0.398; 95% CI 0.22-0.71; P=0.002). These results suggest that the two promoter polymorphisms of VEGF may modify the disease risk in ADPKD patients from North India.