Journal
ARTHRITIS RESEARCH & THERAPY
Volume 17, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13075-015-0585-6
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Funding
- Portuguese Fundacao para a Ciencia e a Tecnologia [PTDC/SAU-GMG/098937/2008, PTDC/IIM-GES/5015/2012, CMUP-ERI/TPE/0028/2013, SFRH/BD/43895/2008, SFRH/BPD/35737/2007, SFRH/BPD/70008/2010]
- Research Committee of the Tehran University of Medical Sciences [132/714]
- Fundação para a Ciência e a Tecnologia [PTDC/SAU-GMG/098937/2008, SFRH/BPD/35737/2007, PTDC/IIM-GES/5015/2012, CMUP-ERI/TPE/0028/2013, SFRH/BD/43895/2008] Funding Source: FCT
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Introduction: The aim of this study was to characterize the association of human leukocyte antigen (HLA) B alleles and major histocompatibility complex (MHC) single nucleotide polymorphisms (SNPs) with Behcet's disease (BD) in an Iranian dataset. Methods: The association of three SNPs in the MHC region previously identified as the most associated in high-density genotyping studies was tested in a case-control study on 973 BD patients and 825 controls from Iran, and the association of HLA-B alleles was tested in a subset of 681 patients and 414 controls. Results: We found that HLA-B*51 (P = 4.11 x 10(-41), OR [95% CI] = 4.63[3.66-5.85]) and B*15 confer risk for BD (P = 2.83 x 10(-2), OR [95% CI] = 1.75[1.08-2.84]) in Iranian, and in B*51 negative individuals, only the B*15 allele is significantly associated with BD (P = 2.51 x 10(-3), OR [95% CI] = 2.40[1.37-4.20]). rs76546355, formerly known as rs116799036, located between HLA-B and MICA (MHC class I polypeptide-related sequence A), demonstrated the same level of association with BD as HLA-B*51 (P-adj = 1.78 x 10(-46), OR [95% CI] = 5.46[4.21-7.09], and P-adj = 8.34 x 10(-48), OR [95% CI] = 5.44[4.20-7.05], respectively) in the HLA-B allelotyped subset, while rs2848713 was less associated (P-adj = 7.14 x 10(-35), OR [95% CI] = 3.73[2.97-4.69]) and rs9260997 was not associated (P-adj = 1.00 x 10(-1)). Additionally, we found that B*51 genotype-phenotype correlations do not survive Bonferroni correction, while carriers of the rs76546355 risk allele predominate in BD cases with genital ulcers, positive pathergy test and positive BD family history (2.31 x 10(-4) <= P <= 1.59 x 10(-3)). Conclusions: We found that the HLA-B*51 allele and the rs76546355/rs116799036 MHC SNP are independent genetic risk factors for BD in Iranian, and that positivity for the rs76546355/rs116799036 risk allele, but not for B*51, does correlate with specific demographic characteristics or clinical manifestations in BD patients.
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