Neri T M, Cavestro G M, Seghini P, Zanelli P F, Zanetti A, Savi M, Podda M, Zuin M, Colombo M, Floreani A, Rosina F, Bianchi Porro G, Strazzabosco M, Okolicsanyi L
Department of Internal Medicine, Nephrology and Health Sciences, University of Parma, Parma, Italy.
Dig Liver Dis. 2003 Aug;35(8):571-6. doi: 10.1016/s1590-8658(03)00274-3.
In patients with with primary sclerosing cholangitis we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
In 64 PSC patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, HLA-DQB1 and HLA-B, tumour necrosis factor A (TNFA), and in CFTR gene, with polymerase chain reaction-based methodologies.
Frequencies of DRB101, DQA10101, DQB10102 (14 vs. 8%, p<0.05), DRB116, DQA10102, DQB10502 (8 vs. 3%, p<0.025) and DRB104, DQA103, DQB10301 (10 vs. 4%, p<0.005) haplotypes were more elevated in PSC patients. The frequency of patients positive for HLA DRB101, 1601 or 04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). DRB107, DQA10201, DQB102 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing HLA-DRB101, 1601, 04 related haplotype sharing patients, HLA-DRB103, DQA10501, DQB1*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in PSC patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased.
These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries.
在原发性硬化性胆管炎患者中，我们研究了主要组织相容性复合体（MHC）基因以及囊性纤维化跨膜传导调节因子（CFTR）基因的突变情况。
在64例原发性硬化性胆管炎患者和183例来自同一人群（意大利北部）的正常对照中，采用基于聚合酶链反应的方法，对MHC区域基因：HLA - DRB1、HLA - DQB1和HLA - B、肿瘤坏死因子A（TNFA）以及CFTR基因的DNA水平等位基因多态性进行了研究。
PSC患者中DRB101、DQA10101、DQB10102单倍型（14%对8%，p<0.05）、DRB116、DQA10102、DQB10502单倍型（8%对3%，p<0.025）以及DRB104、DQA103、DQB10301单倍型（10%对4%，p<0.005）的频率更高。HLA DRB101、1601或04相关单倍型阳性患者的频率显著增加（32%对14%，p<0.00025）。DRB107、DQA10201、DQB102单倍型频率显著降低（4%对15%，p<0.001）。在去除HLA - DRB101、1601、04相关单倍型共享患者后，HLA - DRB103、DQA10501、DQB1*02单倍型频率显著增加（32%对14%，p<0.01）。PSC患者中TNFA2等位基因频率显著增加（23%对14%，p<0.025），TNFA2纯合基因型频率也显著增加（9%对0.5%，p = 0.0013）。CFTR基因未发现突变，内含子8中5T多态性的等位基因频率也未增加。
这些数据表明，HLA区域基因起相关作用，但不一定具有疾病特异性，在不同祖先的人群中可能有所不同。
