Association of CCR1, KLRC4, IL12A-AS1, STAT4, and ERAP1 With Behcet's Disease in Iranians

作者：Sousa Ines; Shahram Farhad; Francisco David; Davatchi Fereydoun; Abdollahi Bahar Sadeghi; Ghaderibarmi Fahmida; Nadji Abdolhadi; Shafiee Niloofar Mojarad; Xavier Joana M; Oliveira Sofia A^*

来源：Arthritis & Rheumatology, 2015, 67(10): 2742-2748.

DOI：10.1002/art.39240

Objective. To independently replicate the top findings from 4 published genome-wide association studies (GWAS) of susceptibility genes in Behc, et'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 x 10(-9) <= P-allele <= 7.55 x 10(-3)) and sex-adjusted genotypic association tests (6.01 x 10(-9) <= adjusted P value <= 1.30 x 10(-2)). For all 6 SNPs tested by meta-analysis (P-meta), 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], P-meta = 52.34 x 10(-16); for rs7616215, OR for C allele 0.70 [95% CI 0.65-0.76], P-meta=1.54 x 10(-19); for rs17810546, OR for A allele 0.60 [95% CI 0.52-0.70], P-meta=6.34 3 10 211; for rs2617170, OR for T allele 0.76 [95% CI 0.70-0.81], P-meta=2.75 3 10 214; for rs13154629, OR for TT genotype 2.76 [95% CI 2.01-3.80], P-meta=3.57 x 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.

• 出版日期2015-10