Research On The Correlation Between TRPC6 Gene Polymorphism And Its Serological Level And Primary Nephrotic Syndrome In Children Of Zhuang Nationality In Guangxi

Objective:To investigate the relationship between the locus polymorphisms of rs3802829,rs12805398,rs12366144,rs3824934,rs7105083,rs10501986 of TRPC6 gene and the occurrence and development of primary nephrotic syndrome in children of Zhuang nationality in Guangxi.To analyze the correlation between polymorphism of six loci above-mentioned and theraputic effects of glucocorticoid therapy on PNS.To study the expression level of TRPC6 protein in serum of children of Zhuang nationality in Guangxi with PNS and analyze its significance.Methods:We included 155 children with PNS and 100 healthy children of Zhuang nationality in Guangxi as the research objects and collected their blood samples for Case-control Study.Children with PNS of Zhuang nationality in Guangxi were divided into groups according to the effect of glucocorticoid therapy,then using the second generation gene sequencing technology to carry out the genotyping of TRPC6 gene rs3802829,rs12805398,rs12366144,rs3824934,rs7105083 and rs10501986.We used the Hardy-Weinberg equilibrium law to test the group representation of the sample,applied SPSS26.0 statistical software to analyze the experimental data,and compared the differences in genotype and allele distribution of the above-mentioned loci between the groups by using Chi-square test or fisher exact probability method.The Logistic regression test was performed to assess the correlation between TRPC6 gene polymorphism and PNS susceptibility and glucocorticoid therapy effect of children of Zhuang nationality in Guangxi,and TRPC6 serum level was detected by enzyme-linked immunosorbent assay.Moreover,the nonparametric rank sum test of two independent samples was used to analyze the difference in its expression between groups.Results:(1)A total of two genotypes GG,GA were detected in PNS group at rs3802829 site with the distribution frequencies of GG: 85.58% and GA: 14.2%.While three genotypes of GG,GA,AA were detected in healthy control group with the distribution frequencies of GG:66%,GA:32%,AA:2%.The genotype frequencies of PNS group were analyzed under three analytical models of co-dominant,dominant and recessive to compare with those of the healthy control group.The differences in genotype distribution between the PNS group and the healthy control group under the co-dominant model(GG vs GA)and dominant model(GG vs GA+AA)were statistically significant(p < 0.05).The difference in their allele frequencies between the PNS group and healthy controls was statistically significant(χ~2=14.34 p=0.0002).The logistic regression analysis was performed under the models of co-dominance,dominance,ressive and additition.The results suggested that GA genotype,GA+AA genotype and A allele may be associated with the risk of PNS.After further exclusion of the confounding factors such as gender and age,the logistic regression correction showed that GA genotype was related to the risk of PNS.(OR:0.309,95%CI:0.126-0.758,p=0.0103).GA+AA genotype was related to the risk of PNS(OR : 0.296,95%CI :0.122-0.719,p=0.0072).A allele was related to the risk of PNS(OR:0.299,95%CI:0.125-0.718,p=0.0069).(2)The differences in genotype frequencies and allele frequencies at rs12805398,rs12366144,rs3824934,rs7105083 and rs10501986 loci were not statistically significant between the PNS group and healthy controls group(p > 0.05).The logistic regression analysis was carried out under the models of co-dominance,dominance,ressive and additition,and the logistic regression correction was carried out after further exclusion of the confounding factors such as gender and age.The results of the both analyses indicated that the genotype distribution and allele distribution of each site were not related to the risk of SRNS(P > 0.05).(3)The differences in genotype frequencies and allele frequencies at loci mentioned above were not statistically significant between the SSNS group and SRNS group(p > 0.05).The logistic regression analysis was carried out under the models of co-dominance,dominance,ressive and additition,and the logistic regression correction was carried out after further exclusion of the confounding factors such as gender and age.The results of the both analyses indicated that the genotype distribution and allele distribution of each site were not related to the risk of(P > 0.05).(4)Serum TRPC6 concentration in PNS group was2.00(0.93,4.88)ng/mL,while that in healthy control group was 3.60(2.10,6.70)ng/mL,which was significantly lower in the PNS group than that in healthy control group(Z =-3.29,P<0.001).The serum TRPC6 concentration was 2.30(1.10,4.40)ng/mL in SSNS group and1.65(0.78,8.18)ng/mL in SRNS group.There was no significant difference between the two groups in terms of TRPC6 serum concentration(Z =-0.474,P=0.636).Conclusion:(1)SNP at rs3802829 may be related to the occurrence of PNS in children of Zhuang nationality in Guangxi,in which GA genotype,GA+AA genotype and A allele may reduce the risk of PNS development in children of Zhuang nationality in Guangxi.(2)SNPs at rs12805398,rs12366144,rs3824934,rs7105083 and rs10501986 are not related to the development of PNS in children of Zhuang nationality in Guangxi.(3)The polymorphisms of rs3802829,rs12805398,rs12366144,rs3824934,rs7105083 and rs10501986 may not be related to the effect of PNS hormone therapy in children of Zhuang nationality in Guangxi.(4)TRPC6 may act as a protective protein in the initial stage of PNS.