AMINO-ACID SUBSTITUTIONS AT POSITION-38 OF THE DR-BETA POLYPEPTIDE CONFER SUSCEPTIBILITY TO AND PROTECTION FROM PRIMARY SCLEROSING CHOLANGITIS
AMINO-ACID SUBSTITUTIONS AT POSITION-38 OF THE DR-BETA POLYPEPTIDE CONFER SUSCEPTIBILITY TO AND PROTECTION FROM PRIMARY SCLEROSING CHOLANGITIS
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DOI：
10.1002/hep.1840160217
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发表时间：
1992-08-01
期刊：
影响因子：
13.5
通讯作者：
WILLIAMS, R
中科院分区：
文献类型：
--
作者：
FARRANT, JM;DOHERTY, DG;WILLIAMS, R
以前的研究基于血清学HLA表型有牵连的基因在HLA II类区域的易感性和保护原发性硬化性胆管炎。在最近的一份报告中，HLA DRw52a抗原存在于所有29例肝移植患者中。在这项研究中，HLA DRB，DQA和DQB基因型进行了研究，采用基因扩增和序列特异性寡核苷酸探针在71例原发性硬化性胆管炎和68名健康对照，以确定频率的DRB 3 * 0101等位基因的患者编码DRw52a和其他II类等位基因是否参与易感性或保护。DRB3 * 0101是最强相关的等位基因，存在于55%的患者和22%的对照中。与DRB 3 * 0101阴性患者相比，DRB 3 * 0101阳性患者的生存率降低。DRB 3 * 0101和DRB 5 * 0101（可能的第二个DRB易感性等位基因）都编码DR-β分子38位的亮氨酸残基。DRB4 * 0101等位基因编码DRw53并可能是保护性的，在该位置编码丙氨酸残基。对原发性硬化性胆管炎的易感性和对原发性硬化性胆管炎的保护可能是由于DR-β分子38位的氨基酸取代，因为最大的相对风险由两个含亮氨酸-38的DR-β分子赋予，而最小的相对风险由两个含丙氨酸-38的DR-β分子赋予。
Previous studies based on serological HLA phenotyping have implicated genes in the HLA class II region in susceptibility to and protection from primary sclerosing cholangitis. In a recent report, the HLA DRw52a antigen was present in all 29 patients who had been referred for liver transplantation. In this study, HLA DRB, DQA and DQB genotypes were studied using gene amplification and sequence-specific oligonucleotide probing in 71 patients with primary sclerosing cholangitis and 68 healthy controls to determine the frequency among the patients of the DRB3*0101 allele that encodes DRw52a and whether other class II alleles are involved in susceptibility or protection. DRB3*0101 was the most strongly associated allele, being present in 55% of the patients and 22% of the controls. Survival among the DRB3*0101-positive patients was reduced compared with the DRB3*0101-negative patients. Both DRB3*0101 and DRB5*0101, a possible second DRB susceptibility allele, encode a leucine residue at position 38 of the DR-beta molecule. The DRB4*0101 allele, which encodes DRw53 and may be protective, encodes an alanine residue at this position. Susceptibility to and protection from primary sclerosing cholangitis may result from amino acid substitutions at position 38 of the DR-beta 'molecule because maximum relative risk was conferred by two leucine-38-containing DR-beta molecules, whereas minimum relative risk was conferred by two alanine-38-containing molecules.