Bernal W, Moloney M, Underhill J, Donaldson P T
Institute of Liver Studies, King's College Hospital and King's College School of Medicine and Dentistry, London, UK.
J Hepatol. 1999 Feb;30(2):237-41. doi: 10.1016/s0168-8278(99)80068-3.
BACKGROUND/AIMS: Primary sclerosing cholangitis is associated with the HLA haplotypes A1-B8-DRB30101-DRB10301-DQA10501-DQB10201 and DRB30101-DRB11301-DQA10103-DQB1 0603. However, the interpretation of these genetic associations is controversial. One explanation may be that HLA-encoded susceptibility is due to other genes carried on these haplotypes such as the HLA class III tumor necrosis factor genes. The aim of the study was to investigate tumor necrosis factor genetics in a large series of well-defined patients.
One hundred and ten HLA genotyped patients and 126 control subjects were studied by polymerase chain reaction genotyping for 3 different tumor necrosis factor gene polymorphisms: -308, -238 and an Ncol restriction fragment length polymorphism in the lymphotoxin alpha gene.
Overall, 58% of patients had the TNF2 allele, compared with 29% of controls, p(c) = 0.0001. No association was found with either of the other tumor necrosis factor polymorphisms examined. TNF2 was significantly increased in the presence of B8 and DRB30101 only, and was independent of DRB10301 (p(c)<0.04). The associations with B8 and TNF2 were stronger than the associations with any of the HLA class II alleles examined.
HLA-encoded genetic susceptibility to primary sclerosing cholangitis may be determined by polymorphism within the HLA class III region, in particular with the TNF2 allele.
背景/目的：原发性硬化性胆管炎与HLA单倍型A1 - B8 - DRB30101 - DRB10301 - DQA10501 - DQB10201以及DRB30101 - DRB11301 - DQA10103 - DQB10603相关。然而，这些基因关联的解释存在争议。一种解释可能是，HLA编码的易感性归因于这些单倍型上携带的其他基因，如HLAⅢ类肿瘤坏死因子基因。本研究的目的是在大量明确诊断的患者中研究肿瘤坏死因子遗传学。
采用聚合酶链反应基因分型技术，对110例HLA基因分型患者和126例对照者进行3种不同肿瘤坏死因子基因多态性研究：-308、-238以及淋巴毒素α基因中的NcoI限制性片段长度多态性。
总体而言，58%的患者具有TNF2等位基因，而对照组为29%，p(c)=0.0001。在所检测的其他肿瘤坏死因子多态性中未发现关联。仅在存在B8和DRB30101时，TNF2显著增加，且与DRB10301无关（p(c)<0.04）。与B8和TNF2的关联比与所检测的任何HLAⅡ类等位基因的关联更强。
HLA编码的原发性硬化性胆管炎遗传易感性可能由HLAⅢ类区域内的多态性决定，尤其是TNF2等位基因。
