## 4 Discussion  
There are some reports in the literature about the association between rs626277, rs7805747, and rs11959928 genetic variants and CKD. However, the effect of these genetic variants on CKD according to gender has not been revealed. We investigated these three SNPs in female and male patients with CKD. Our association study demonstrated that rs7805747 has a protective effect on females. However, this SNP and rs11959928 increased the risk of CKD in male patients. The present results suggest that some polymorphism affects the development of CKD in contrasting ways in males and females. Complex diseases have multiple genetic and environmental background risk factors. Genome-wide association study with its ability to scan many genetic variations has emerged recently to find such susceptibility variants. HRM offers a low-cost, sensitive, convenient, and closed-tube method for single-nucleotide discrimination and easy combination with real-time PCR [17]. Moreover, the close-tube approach decreases the risk of contamination. Megalin plays a crucial role in the process of filtered low molecular weight protein endocytosis in the apical region of renal proximal tubular cells. DAB2, as an intracellular adaptor, regulates megalin trafficking [18]. Our investigation also showed a more than two-fold increase in CKD because of the presence of rs11959928 variation in males. In multiple GWAS, the rs11959928 variation has been linked to CKD [19]. However, neither the Genotype-Tissue Expression (GTEx25) nor the gene expression variation (eQTLs; [[https://www.eetlgen.org/](https://www.eetlgen.org/)]([https://www.eetlgen.org/](https://www.eetlgen.org/)), accessed on 1 June 2017) datasets showed any correlation between this variation and changes in gene expression [20]. It is assumed that DAB2 in CKD plays a role in the renal tubule cells and the endolysosomal pathway [6]. They came to the conclusion that tubular fibrosis is caused by higher expressed levels of DAB2 in tubule cells, which is linked to the DAB2 locus in CKD. Reducing DAB2 expression in renal tubules protected mice from CKD, according to functional tests [6]. The degree of CKD was significantly lower in DAB2 knock-out mice compared with wild-type mice with folic acid-induced kidney injury. These studies have found rs11959928 to be associated with a higher CKD risk, but without accounting for sex heterogeneity. In our study, the rs7805747 dominant model demonstrated more than four times the odds of kidney involvement in males even after adjustment for age, C-reactive protein, body mass index, diabetes mellitus, and smoking. This variant had the opposite effect on females. [PERSON] et al. highlighted the role of PRKAG2 in the metabolic functions of the kidney [19]. It has also been mentioned that PRKAG2 may cause enlarged kidneys [21]. With a genome-wide significance level, PRKAG2 was found to be significantly linked with both serum creatinine and CKD [22]. Comprehensive functional analysis using multiple bioinformatics databases reported this variant to be associated with serum creatinine [13]. It has been reported that 5'-AMP-activated protein kinase (AMPK), as a metabolic enzyme, plays a role in regulating energy metabolism in response to cellular stress [23]. The presence