Marrosu M G, Muntoni F, Murru M R, Spinicci G, Pischedda M P, Goddi F, Cossu P, Pirastu M
Istituto di Neuropsichiatria Infantile, Università degli Studi di Cagliari, Italy.
Neurology. 1988 Nov;38(11):1749-53. doi: 10.1212/wnl.38.11.1749.
HLA haplotypes in 45 unrelated Sardinian multiple sclerosis patients and in six multiplex families were defined, using both serologic and restriction fragment length polymorphism (RFLP) analysis. In unrelated MS patients, we found an association with HLA-DR4 (p less than 0.01, relative risk = 2.5) and DQw3 (p less than 0.04, relative risk = 2.2). Using a beta-DR cDNA probe, we observed no variation of the DR4 RFLP profile in sporadic or related MS patients compared with DR4-specific pattern in controls. Using a beta-DQ cDNA probe, we identified two DQw3 patterns (DQw3.1 and DQw3.2) with similar frequency in patients and in controls. No specific RFLPs were observed in association with different disease courses. The frequency of haplotype sharing in affected members of multiplex families was not different from that expected by chance. This study shows that Sardinian MS patients carry predominantly the HLA-DR4 allele, in contrast to the DR2 prevalence reported in Caucasian populations. The lack of association with HLA haplotypes in affected members of multiplex families may indicate that genetic factors outside the HLA system play a substantial role in families with MS.
运用血清学和限制性片段长度多态性（RFLP）分析，对45名无亲缘关系的撒丁岛多发性硬化症患者以及6个多成员家庭进行了HLA单倍型分型。在无亲缘关系的多发性硬化症患者中，我们发现其与HLA - DR4（p小于0.01，相对风险 = 2.5）和DQw3（p小于0.04，相对风险 = 2.2）存在关联。使用β - DR cDNA探针，我们观察到散发性或家族性多发性硬化症患者的DR4 RFLP图谱与对照组中DR4特异性图谱相比没有差异。使用β - DQ cDNA探针，我们在患者和对照组中识别出两种频率相似的DQw3图谱（DQw3.1和DQw3.2）。未观察到与不同病程相关的特定RFLP。多成员家庭中患病成员的单倍型共享频率与随机预期频率没有差异。这项研究表明，与高加索人群中报告的DR2流行情况相反，撒丁岛多发性硬化症患者主要携带HLA - DR4等位基因。多成员家庭中患病成员与HLA单倍型缺乏关联可能表明，HLA系统以外的遗传因素在多发性硬化症家庭中起重要作用。
