Association of urokinase and Vitamin D receptor genes SNPs and urolithiasis in an Iraqi population

Abstract

BackgroundSeveral genetic polymorphisms have been supposed to participate in urolithiasis progression. We investigated the association of the urokinase gene 3’-UTR and vitamin D receptor (VDR) polymorphisms with urolithiasis in an Iraqi population. MethodsTotally, 104 first kidney stone formers (63 males and 41 females), 100 recurrent stone formers (56 males and 44 females) and 127 healthy subjects (71 males and 56 females) were enrolled. The DNA was extracted from the peripheral blood; next the urokinase 3’-UTR and vitamin D receptor (VDR) genes polymorphisms (rs4065 and rs731236, respectively) were evaluated using polymerase chain reaction (PCR) and PCR- restriction fragment length polymorphism (RFLP) using ApaL I and Taq1 restriction enzymes, respectively. ResultsThere was a significant difference between those who had urolithiasis with familial history and those patients without history (179 vs 25, p < .001). TT genotype (rs4065 polymorphism) was predominant among first-time stone formers (73/104, 70.2%) and recurrent stone formers (84/100, 84%) as compared to control group (42/127, 33.1%) (p = .002 and p < .001, respectively). CC genotype was significantly higher in recurrent stone formers (20/100, 20%) than first-time stone formers (8/104, 7.7%, p = .022). Notably, total stone formers had significant more rs4065 SNP (157/204 or 76.96% vs. 33.1%, p < .001) than control group (76.96 vs 33.1%, p < .001). Furthermore, VDR CC genotype (rs731236 polymorphism) of stone formers (18%) was significantly higher than control (12/127, 9.44%) (p = .030 and p = .021, respectively). Control group had significantly higher rate of CG than those from other groups. Using multinomial logistic analysis, urokinase TT genotype and VDR CC genotype were associated with urolithiasis. ConclusionThere was a significant association between urokinase gene 3’-UTR TT (rs4065) and VDR genes (rs731236) polymorphisms urolithiasis. In addition, VDR CC genotype was significantly associated with recurrent urolithiasis. However, more in-depth verifications will be helpful towards disclosure of genetic mutations predisposing first-time and recurrent urolithiasis.