Global rise in the prevalence of endemic chronic kidney disease of unknown etiology (CKDu) possess major health issues. The prevalence of CKDu is also rising in the Indian population. Besides environmental factors, genetic factors play an important role in the predisposition to CKDu. In the present study, we have analyzed the association of single nucleotide polymorphisms (SNPs) in three genes with the susceptibility to CKDu. This was a case-control study with a total of 180 adult subjects (CKD = 60, CKDu = 60, Healthy = 60) from central India. We performed KASP genotyping assay to determine the allele frequency of SNP genotypes. We used the odds ratio (OR) to assess the association of individual SNPs, rs34970857 of KCNA10, rs6066043 of SLC13A3, and rs2910164 of miR-146a with CKDu and CKD susceptibility. In the case of rs34970857 of the KCNA10 gene, we noted a significantly increased OR for CKDu versus healthy control (Dominant model; CKDu versus control, CT + CC versus TT, OR = 3.96, p = 0.004). In the recessive and homozygous model, we observed significantly increased OR for rs6066043 of SLC13A3 gene, CKDu versus healthy control {(Recessive model; CKDu versus control, GG versus AA + GA, OR = 2.41, p = 0.03; homozygous model, GG versus AA, OR = 3.54, p = 0.04)}. CC genotype of rs34970857 of the KCNA10 gene and the GG genotype of the SLC13A3 gene are significantly associated with the susceptibility of CKDu.