Polymorphisms in genetics of vitamin D metabolism confer susceptibility to ocular Behçet disease in a Chinese Han population.

PURPOSE: To test whether single nucleotide polymorphisms (SNPs) of the 4 vitamin D family genes (DHCR7, CYP2R1, CYP27B1, and CYP24A1) previously associated with several autoimmune diseases are associated with ocular Behçet disease, Vogt-Koyanagi-Harada (VKH) syndrome, acute anterior uveitis (AAU) with ankylosing spondylitis, or pediatric uveitis in the Chinese Han population.

DESIGN: Prospective case-control study.

METHODS: Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism, and the genotypes were verified with direct sequencing. The first-stage study comprised 400 ocular Behçet disease patients, 400 VKH syndrome patients, 218 AAU with ankylosing spondylitis patients, 400 pediatric uveitis patients, and 600 healthy subjects from Chinese Han populations. The second stage included 427 ocular Behçet disease patients and 1000 healthy Chinese Han subjects. Allele and genotype frequencies were compared between patients and controls using the χ(2) test.

RESULTS: In the first-stage study, only the frequencies of the rs12785878 DHCR7 genotype TT and T allele were significantly higher in ocular Behçet disease patients (P = .036 and P = .008 with Bonferroni correction, respectively) compared with controls among 6 SNPs. No associations could be detected for VKH, AAU with ankylosing spondylitis, or pediatric uveitis. A second stage and combined study confirmed the association of rs12785878 DHCR7 TT genotype and T allele with ocular Behçet disease (P = 3.28E-04 with Bonferroni correction; odds ratio, 1.506; 95% confidence interval, 1.248 to 1.818; and P = 2.82E-05 with Bonferroni correction; odds ratio, 1.339; 95% confidence interval, 1.188 to 1.508, respectively).

CONCLUSIONS: This study provides evidence that the DHCR7 gene is involved in the susceptibility to ocular Behçet disease.