Associations Between Vitamin D Receptor Gene Polymorphisms And Systemic Sclerosis

Objective:We aimed to investigate the association between the Vitamin D receptor(VDR)gene polymorphisms and systemic sclerosis(SSc)in Chinese Han population.Methods:With a case-control study design,the latest SSc patients who met the SSc diagnostic criteria of the American College of Rheumatology in 1980 were collected from the Department of Rheumatology and Immunology of the First Affiliated Hospital of Anhui Medical University and the First Affiliated Hospital of the University of Science and Technology of China(Anhui Provincial Hospital).At the same time,according to the principle of frequency matching,100 unrelated volunteerswere collected as health control group from the First Affiliated Hospital of Anhui Medical University.There have 8 SNPs of VDR gene were selected as candidates,including rs731236[TaqI],rs2228570[FokI],rs7975232[ApaI],rs1544410[BsmI]and rs11574010[Cdx2],rs739837[BglI],rs757343[Tru 9I]and rs11168267;the 8 SNPs were genotyped using Improved Multi-Ligase Detection Reaction(iMLDR)technology,and construct the dominant,recessive,super-dominant and homozygous model to analyze the distribution of these SNPs between the SSc patients and the control group.At the same time,we performed linkage disequilibrium(LD)detection and haplotype analysis in the 8 SNPs.Finally,we also analyzed the relationship between the distribution of genotypes of the 8 SNPs and the clinical and laboratory parameters of SSc patients.Results:The average age in SSc patients(male/female:12/88)was 48.63±12.55 years,the course of the disease was 0.5~10 years;and the average age in controls were47.47±10.41 years(male/female:19/81).There were no statistical difference between the SSc patients and controls in sex and age(P>0.05)was found.Hardy-Weinberg Equilibrium(HWE)test found that these 8 polymorphisms are in accordance with the Genetic Equilibrium Law in controls;in addition,the D'map of Linkage Disequilibrium(LD)analysis showed that these controls selected in this study were similar to the results of CHB population in the HapMap database,which show that the control has a good representation.Statistically significant difference were found in the ApaI and BglI polymorphisms between SSc patients and controls.The ApaI polymorphism CA genotypewashigherinSScgroupthanthatincontrols(OR[95%CI]=2.154[1.201,3.863],?~2=6.624,P=0.010).The BglI polymorphism GT genotype was also higher in SSc patients than that in controls(OR[95%CI]=6.424[1.285,32.116],?~2=5.132,P=0.023).However,after correction by the Bonferroni method,the difference were no longer statistically significant(P>0.00625).But our results showed that there were no significant difference in these clinical symptoms and markers.In addition,the dominant model of ApaI(rs7975232)and recessive model of BglI(rs739837)have also showed the ApaI(rs7975232)and BglI(rs739837)polymorphisms were associated to SSc(OR(95%CI)=0.556[0.317,0.975],P=0.041 and OR(95%CI)=1.799[1.025,3.156],P=0.041,respectively).However,after correction by the Bonferroni method,the difference were no longer statistically significant(P>0.00625).There was high linkage disequilibrium was detected in BglI and ApaI polymorphisms(r~2=1.0,D?=1.0),Tru9I and rs11168267(r~2=0.926,D?=0.969),respectively.Moreover,haplotype analysis were also evaluated through the distribution of haplotypes in SSc versus controls.However,no significant difference were found in these four haplotypes(P>0.05).Conclusions:1.The over-dominant model of the ApaI and BglI polymorphism of VDR gene polymorphism may be associated with SSc;however,other 6 polymorphisms may not be associated with the susceptibility of SSc.2.There were no significant difference between these 8 polymorphisms of the VDR gene and the clinical manifestations of SSc patients.