| Objective: We aimed to investigate the role of vitamin D receptor(VDR) gene polymorphisms in ankylosing spondylitis(AS) susceptibility.Methods: With a case-control design, 620 AS patients from the department of Rheumatology and Immunology, the 1st Affiliated Hospital of Anhui Medical University were enrolled, and all of them fulfill the modified New York criteria in 1984. All 620 healthy controls that were frequency matched by age, sex and race with AS cases were recruited from the Blood Center of Hefei. A total of 4 single nucleotide polymorphisms(SNPs) locate in VDR gene were selected as candidates(Fok I(rs2228570)、Bsm I(rs1544410), Apa I(rs7975232) and Taq I(rs731236)). Improved Multi-Ligase Detection Reaction(i MLDR) technology was performed to genotyping these SNPs. Genotype, allele, dominant model, recessive model, homozygous model and over-dominance model were used to compare the distributions of the 4 SNPs in AS and controls. Linkage disequilibrium and haplotype analyses were also performed in the 4 SNPs. In addition, we have also analyzed the associations between the distribution of genotypes of the 4 SNPs and clinical characteristics(BASDAI and BASFI) in AS group. Due to the different risk of AS morbidity in male and female, we carried out a stratificational analysis by sex. Continuous data with normalized distribution were given as mean ± standard deviation(SD), while non-normalized continuous data were shown as median(interquartile range, IQR). Statistical analysis was performed by SPSS 16.0 software. Two-tailed P < 0.05 in this study was considered as statistically significant. Bonferroni correction was used for multiple comparisons.Results: The average age in AS patients(male/female: 515/105) was 28.3 ± 9.0 years, and 27.8 ± 7.6 years in controls(male/female: 512/108). No statistically difference between AS patients and controls in sex(χ~2 = 0.051, P = 0.821) and age(t = 0.957, P = 0.339) was found. The positive rate of HLA-B27 in AS patients was 93.9%, and the average course, BASDAI and BASFI were 2.00(6.00) years, 1.77(2.90) and 0.90(2.35), respectively. Hardy-Weinberg Equilibrium(HWE) test found the Fok I(rs2228570) polymorphism in controls was statistically significant(P = 0.002). There were significantly differences in Taq I(rs731236) polymorphism between AS group and controls in the genotype(χ~2 = 6.845, P = 0.018), allele frequency(χ~2 = 6.705, OR [95%CI] = 1.624 [1.122-2.352], P = 0.006), dominant model(χ~2 = 6.728, OR [95%CI] = 1.656 [1.128-2.431], P = 0.010) and over-dominance model(χ~2 = 6.476, OR [95%CI] = 0.606 [0.411-0.894], P = 0.012), after Bonferroni correction, the differences were remain significant in allele frequency, dominant model and over-dominance model(all P < 0.0125). Interestingly, after stratificational analysis by sex, the differences of distribution in these genetic models were only found between male, but not between females. Linkage disequilibrium test found there was a strong linkage between Taq I(rs731236) and Bsm I(rs1544410) polymorphisms, and haplotype analysis suggested the two types of Taq I-Bsm I haplotype were significantly difference between AS and controls(H1: OR [95%CI] = 0.671 [0.473-0.952], P = 0.022; H2: OR [95%CI] = 1.516 [1.012-2.270], P = 0.042). Clinical characteristic analysis in AS group found a significant association between the distribution of Fok I(rs2228570) genotypes and BASFI score(χ~2 = 12.025, P = 0.002), while there was no other associations between the genotypes of the other 3 SNPs and BASDAI or BASFI score, and stratificational analysis also found that the distribution of Fok I genotypes were associated with BASFI score only in male AS patients(χ~2 = 9.825, P = 0.007), but not in females.Conclusions: VDR gene Taq I(rs731236) polymorphism G allele may play a risk factor in AS susceptibility and Fok I(rs2228570) genotype may involve in AS severity. VDR gene may influence the risk and severity of AS especially in male patients. |
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