Implication of podocin promoter variant haplotype in south Indian diabetic kidney patients

Type 2 diabetes (T2D) is a global epidemic, 40% of T2D individuals are associated with diabetic kidney disease (DKD) a major microvascular complication leading to end stage renal disease (ESRD). We aimed to screen for three podocin (NPHS2) gene promoter variants -535ins/del (CTTTTTTT)2, rs1079291(C > T) and rs12406197 (G > T) in T2D and DKD patients of south India to explore their role in the propensity to DKD. The present study enrolled a total of 200 T2D patients comprising an equal number of T2D and DKD patients and performed genotyping using PCR followed by Sanger sequencing. Individual genotype analysis performed for three podocin promoter variants yielded different results. -535 ins/del (CTTTTTT)2 and rs1079291(C > T) gene variants showed lack of association. However, the GG vs. GT + TT genotype of rs12406197(G > T) exhibited protective effect (OR = 0.51; 95% CI = 0.28–0.92; p = 0.03). A genotype dependent variation was noted with respect to rs1079291 mutant genotype for serum albumin, serum creatinine, eGFR and rs12406197 risk genotypes for HbA1c, serum albumin and serum creatinine within the DKD group. Haplotype block 2TT found to be a risk haplotype towards DKD (OR = 2.43; 95% CI = 1.17–5.03; p = 0.017). Diabetic individuals carrying mutant allele and the elevated levels of kidney functioning markers are vulnerable to nephropathy. Further 2TT promoter haplotype appears to play a role in the genetic susceptibility to DKD in south Indian patients suggesting that the low production/depletion of podocin may hinder the regeneration and replacement of podocytes. As the sample size of the present study is limited in order to test our contention large studies are warranted.