Abstract
Background/ObjectiveRAC1 gene could influence susceptibility to renal failure by altering the activity and expression of Rac1, which is a member of the Rho family of small GTP-binding proteins. In clinical practice, renal transplantation provides the optimal treatment for people with end-stage renal disease (ESRD). The objective of this present study was to determine whether the RAC1 gene polymorphisms were associated with primary ESRD susceptibility in Chinese renal recipients.MethodsSix single nucleotide polymorphisms (SNPs) of RAC1 gene, including rs836488 T>C, rs702482 A>T, rs10951982 G>A, rs702483 A>G, rs6954996 G>A, and rs9374 G>A, were genotyped in 300 renal transplant recipients (cases) and 998 healthy Chinese subjects (controls) by using TaqMan SNP genotyping assay. Allele, genotype, and haplotype frequencies of the six SNPs were compared between cases and controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated in logistic regression models to evaluate the associations of the six SNPs with ESRD risk.ResultsThe genotype distributions for the six SNPs in controls were consistent with Hardy-Weinberg equilibrium (P > 0.05). Association analysis revealed that three SNPs were significantly associated with ESRD risk. Positive associations with ESRD risk were found for the rs836488, rs702482, and rs702483 in the co-dominant model (minor allele homozygotes versus major allele homozygotes); specifically, the frequencies of the minor allele homozygotes and the minor allele for the three SNPs were higher in the cases than in the controls. In addition, these three SNPs also had associations with increased ESRD risk under the additive model (P < 0.05), and positive associations were also found for the rs836488 in the dominant model (P < 0.05) and for the rs702483 in the recessive model (P < 0.05). All these associations were independent of confounding factors. The other three SNPs (rs10951982, rs6954996, and rs9374), in all comparison models, were not associated with ESRD risk (P > 0.05). In haplotype analysis, carriers with "C-T-G-G-G-G" haplotype had a significantly higher risk of ESRD compared with the most common haplotype "T-A-G-A-G-G" (P = 0.011, OR = 1.46, 95% CI = 1.09–1.94).ConclusionThis study suggested that polymorphisms of RAC1 gene might influence the susceptibility to ESRD in Chinese Han population. Further studies are necessary to confirm our findings.
Highlights
End-stage renal disease (ESRD), the complete or almost complete failure of the kidneys to function, has become a worldwide public health problem, with increased risks of mortality and morbidity [1, 2]
Positive associations with ESRD risk were found for the rs836488, rs702482, and rs702483 in the co-dominant model; the frequencies of the minor allele homozygotes and the minor allele for the three single nucleotide polymorphisms (SNPs) were higher in the cases than in the controls
There were no significant differences between cases and controls in gender, age, history of alcohol consumption, and smoking status which indicated that the populations were adequately matched (P > 0.05)
Summary
End-stage renal disease (ESRD), the complete or almost complete failure of the kidneys to function, has become a worldwide public health problem, with increased risks of mortality and morbidity [1, 2]. A growing body of studies have focused on associations of genetic polymorphisms in candidate genes with the risk of ESRD [6,7,8,9,10]. The latest developments in genomewide association studies (GWAS) have identified a number of genetic-variants associated with impairment of renal function [1], including MECOM, UNCX, WDR72, UMOD, and GNAS [1, 11,12,13]. Other genes could be candidates and further assessment is desirable
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