| Autor: |
Beretta, Lorenzo, Rueda, Blanca, Marchini, Maurizio, Santaniello, Alessandro, Simeón, Carmen P., Fonollosa, Vicente, Caronni, Monica, Rios-Fernandez, Raquel, Carreira, Patricia, Rodriguez-Rodriguez, Luis, Moreno, Antonia, López-Nevot, Miguel A., Escalera, Ana, González-Escribano, Maria F., Martin, Javier, Scorza, Raffaella |
| Předmět: |
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| Zdroj: |
Rheumatology; Jan2012, Vol. 51 Issue 1, p52-59, 8p, 6 Charts |
| Abstrakt: |
Objective. To determine the role of Class II HLAs in SSc patients from Italy and Spain and in SSc patients of Caucasian ancestry.Methods. Nine hundred and forty-four SSc patients (Italy 392 patients; Spain 452 patients) and 1320 ethnically matched healthy controls (Italy 398 patients; Spain 922 patients) were genotyped up to the fourth digit by PCR with sequence-specific oligonucleotides for HLA-DRB1, DQA1 and DQB1 loci. Patients included 390 ACA-positive and 254 anti-topo I-positive subjects. Associations between SSc or SSc-specific antibodies and HLA alleles or HLA haplotypes were sought via the chi-square test after 10 000-fold permutation testing. A meta-analysis including this study cohort and other Caucasoids samples was also conducted.Results. In both the cohorts, the strongest association was observed between the HLA-DRB1*1104 allele and SSc or anti-topo I antibodies. The HLA-DRB1*1104 -DQA1*0501 -DQB1*0301 haplotype was overrepresented in Italian [odds ratio (OR) = 2.069, 95% asymptotic CIs (CI95) 1.486, 2.881; P < 0.001] and in Spanish patients (OR = 6.707, CI95 3.974, 11.319; P < 0.001) as well as in anti-topo-positive patients: Italy (OR = 2.642, CI95 1.78, 3.924; P < 0.001) and Spain (OR = 20.625, CI95 11.536, 36.876; P < 0.001). In both the populations we also identified an additional risk allele (HLA-DQB1*03) and a protective allele (HLA-DQB1*0501) in anti-topo-positive patients. The meta-analysis showed different statistically significant associations, the most interesting being the differential association between HLA-DRB1*01 alleles and ACAs (OR = 1.724, CI95 1.482, 2.005; P < 0.001) or topo I antibodies (OR = 0.5, CI95 0.384, 0.651; P < 0.001).Conclusions. We describe multiple robust associations between SSc and HLA Class II antigens in Caucasoids that may help to understand the genetic architecture of SSc. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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