Moloney M M, Thomson L J, Strettell M J, Williams R, Donaldson P T
Institute of Liver Studies, King's College School of Medicine and Denistry, London, UK.
Hepatology. 1998 Sep;28(3):660-2. doi: 10.1002/hep.510280309.
Genetic susceptibility to primary sclerosing cholangitis (PSC) is associated with the extended HLA A1-B8-DR3 haplotype and also with the DRB30101-DRB10301-DQA10103-DQB10603 haplotype. However, very few studies have considered the role of HLA C which lies between HLA A and B, is highly polymorphic, and encodes proteins which play an important role in immunoregulation and in disease susceptibility. Traditional assignment of HLA Cw antigens by serology is both inaccurate and unreliable, with a high error rate. The aim of this study was to characterize the distribution of HLA C alleles in a large group of patients with primary sclerosing cholangitis by using a recently developed polymerase chain reaction-based genotyping technique. Ninety-three white adult patients of northern European origin with well characterized PSC and 100 geographically and racially matched controls were studied. HLA C and HLA DRB1 alleles were assigned by polymerase chain reaction-based genotyping, HLA A and B antigens by standard microlymphocytotoxicity test and extended haplotypes were constructed according to known patterns of linkage disequilibrium. The Cw07 gene was found in 67.7% of patients versus 54% of controls (P = .051, OR = 1.79). This increase was a result of inheritance of the Cw0701 allele which was found in 51.6% of patients compared with 34% of controls (P = .013, OR = 2.07). There were no significant differences in the frequencies of any of the other Cw alleles including the Cw07 group: Cw0702, Cw0703, and Cw0704. HLA-encoded genetic susceptibility to PSC is associated with the HLA Cw*0701 allele, but the association is weak and may simply reflect linkage disequilibrium with the HLA B8-DR3 haplotype. These findings indicate that the telomeric limit of HLA-encoded susceptibility to primary sclerosing cholangitis lies close to the HLA C locus.
原发性硬化性胆管炎（PSC）的遗传易感性与扩展的HLA A1 - B8 - DR3单倍型以及DRB30101 - DRB10301 - DQA10103 - DQB10603单倍型相关。然而，很少有研究考虑位于HLA A和B之间、具有高度多态性且编码在免疫调节和疾病易感性中起重要作用的蛋白质的HLA C的作用。通过血清学对HLA Cw抗原进行传统分型既不准确也不可靠，错误率很高。本研究的目的是使用最近开发的基于聚合酶链反应的基因分型技术，对一大群原发性硬化性胆管炎患者中HLA C等位基因的分布进行特征分析。研究了93名来自北欧、具有明确特征的成年白人PSC患者以及100名在地理和种族上匹配的对照。通过基于聚合酶链反应的基因分型确定HLA C和HLA DRB1等位基因，通过标准微量淋巴细胞毒性试验确定HLA A和B抗原，并根据已知的连锁不平衡模式构建扩展单倍型。在67.7%的患者中发现了Cw07基因，而对照中为54%（P = 0.051，OR = 1.79）。这种增加是由于Cw0701等位基因的遗传，在51.6%的患者中发现该等位基因，而对照中为34%（P = 0.013，OR = 2.07）。包括Cw07组（Cw0702、Cw0703和Cw0704）在内的任何其他Cw等位基因的频率均无显著差异。HLA编码的对PSC的遗传易感性与HLA Cw*0701等位基因相关，但这种关联较弱，可能仅仅反映了与HLA B8 - DR3单倍型的连锁不平衡。这些发现表明，HLA编码的对原发性硬化性胆管炎易感性的端粒界限靠近HLA C基因座。
