Haegert D G, Francis G S
Memorial University of Newfoundland, St. John's, Canada.
Hum Immunol. 1992 Jun;34(2):85-90. doi: 10.1016/0198-8859(92)90033-j.
Putative disease susceptibility and resistance HLA class II alleles were studied in 78 French Canadian multiple sclerosis (MS) patients and 79 controls by using sequence-specific oligonucleotide probes to analyze in vitro amplified DNA (PCR-SSOP) typing). In this relatively homogeneous ethnic group, MS was positively associated with DRB50101, DQB10602, and DQA10102 and negatively associated with DQB10301. The strongest disease association was with DQB10602. Complete DQB1 typing of these individuals, plus RFLP DQ beta typing of an additional five patients showed that 98% of patients compared with 73% of controls carry DQB1 alleles encoding leucine at residue 26. In contrast, 16% of patients compared with 38% of controls carry DQB1 alleles encoding tyrosine at the same residue, and 22% of patients versus 44% of controls carry DQB1 alleles encoding glycine at residue 26. The positive disease correlation was confirmed with SSO probes designed to hybridize to codons for amino acids 22-27 of DQB10602, 0603, 0604, 0302, 0303 or to codons for amino acids 25-31 of DQB1*0201; all of these alleles encode Leu 26. These findings suggest that DQ beta chain polymorphisms at a single residue contribute to the development of MS in the French Canadian population.
通过使用序列特异性寡核苷酸探针分析体外扩增的DNA（PCR-SSOP分型），对78名法裔加拿大多发性硬化症（MS）患者和79名对照者的假定疾病易感性和抗性HLA II类等位基因进行了研究。在这个相对同质的种族群体中，MS与DRB50101、DQB10602和DQA10102呈正相关，与DQB10301呈负相关。最强的疾病关联是与DQB10602。对这些个体进行完整的DQB1分型，再加上对另外5名患者进行RFLP DQβ分型，结果显示，98%的患者与73%的对照者携带在第26位残基编码亮氨酸的DQB1等位基因。相比之下，16%的患者与38%的对照者携带在同一残基编码酪氨酸的DQB1等位基因，22%的患者与44%的对照者携带在第26位残基编码甘氨酸的DQB1等位基因。用设计用于与DQB10602、0603、0604、0302、0303的第22 - 27位氨基酸密码子或DQB1*0201的第25 - 31位氨基酸密码子杂交的SSO探针，证实了疾病的正相关性；所有这些等位基因都编码第26位的亮氨酸。这些发现表明，单个残基处的DQβ链多态性有助于法裔加拿大人群中MS的发生。
