Brief report: association of CCR1, KLRC4, IL12A-AS1, STAT4, and ERAP1 With Behçet's disease in Iranians.

OBJECTIVE: To independently replicate the top findings from 4 published genome-wide association studies (GWAS) of susceptibility genes in Behçet's disease (BD). METHODS: We tested 14 single-nucleotide polymorphisms (SNPs) in 13 genomic loci (excluding the major histocompatibility complex [MHC], IL10, and IL23R-IL12RB2, which have already been associated with BD in Iranians) for allelic and genotypic associations with BD in 973 patients and 828 controls from Iran and performed meta-analyses of the significantly associated markers. RESULTS: Six SNPs (in decreasing order of significance, rs7616215 located 38 kb downstream of CCR1, rs2617170 [p.Asn104Ser] in KLRC4, rs17810546 in IL12A-AS1, rs7574070 in STAT4, and rs10050860 [p.Asp575Asn] and rs13154629 in ERAP1) were nominally associated with BD in both allelic association tests (5.05 × 10(-9) ≤ Pallele ≤ 7.55 × 10(-3) ) and sex-adjusted genotypic association tests (6.01 × 10(-9) ≤ adjusted P value ≤ 1.30 × 10(-2) ). For all 6 SNPs tested by meta-analysis (Pmeta ), the association with BD was strengthened, because the direction and magnitude of association were similar across populations (e.g., for rs7574070, odds ratio [OR] for A allele 1.29 [95% confidence interval (95% CI) 1.21-1.37], Pmeta = 2.34 × 10(-16) ; for rs7616215, OR for C allele 0.70 [95% CI 0.65-0.76], Pmeta = 1.54 × 10(-19) ; for rs17810546, OR for A allele 0.60 [95% CI 0.52-0.70], Pmeta = 6.34 × 10(-11) ; for rs2617170, OR for T allele 0.76 [95% CI 0.70-0.81], Pmeta = 2.75 × 10(-14) ; for rs13154629, OR for TT genotype 2.76 [95% CI 2.01-3.80], Pmeta = 3.57 × 10(-10) ). CONCLUSION: This study reinforces the notion that CCR1, KLRC4, IL12A-AS1, STAT4, and ERAP1 are bona fide susceptibility genes for BD, in addition to the MHC, IL10, and IL23R-IL12RB2 loci. Future genetic and functional studies are now warranted to uncover the roles of these genes in the pathogenesis of BD.

Plasma homocysteine level in patients with Behcet's disease with or without thrombosis.

AIM: To find the possible role of plasma homocysteine level as a contributing factor in venous and arterial thrombosis in patients with Behcet's disease (BD). METHODS: In a case control study, two groups of BD patients were included: 47 with thrombosis and 49 without thrombosis. All patients fulfilled the International Study Group Criteria for BD and the confirming diagnostic procedures for vascular thrombosis were either Doppler sonography or angiography. Forty-nine controls were selected by consecutive sampling among age and sex matched healthy subjects. Plasma homocysteine level was measured by ELISA in all. The clinical and laboratory characteristics of the disease were compared between the two groups of BD patients. Comparisons were done by ANOVA and Chi square tests; correlations were analyzed with Pearson test. RESULTS: The mean plasma homocysteine level was significantly higher in BD patients (14.9±13.9 µMol/L) than in healthy controls (9.9±6.7 µMol/L), P<0.02. The difference was also significant when comparing the three groups by ANOVA: BD patients with thrombosis (24.2±13.2 µMol/L), BD patients without thrombosis (5.9±7.0 µMol/L), and healthy controls (P<0.0001). We found no correlation between plasma homocysteine level and any organ involvement other than thrombosis. The mean plasma homocysteine level was lower in HLA-B51 positive BD patients (11.6±12.1 vs. 21.7±16.3 µMol/L, P<0.05), but the difference was not significant in those with thrombosis (20.9±13.2 vs. 29.5±12.7 µMol/L, P=0.18). CONCLUSION: Hyperhomocysteinaemia may be an independent risk factor for vascular thrombosis in patients with BD. This is the first study showing a negative correlation between HLA-B51 and plasma homocysteine level.