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NEUROLOGY 1988;38:1749
© 1988 American Academy of Neurology

Sardinian multiple sclerosis is associated with HLA-DR4

A serologic and molecular analysis

M. G. Marrosu, MD, F. Muntoni, MD, M. R. Murru, BS, G. Spinicci, MD, M. P. Pischedda, MD, F. Goddi, MD, P. Cossu, MD and M. Pirastu, MD

Istituto di Neuropeichiatria Infantile (Dra. Marrosu, Muntoni, Spinicci, Pischedda, and Ms. Murru), Universitá degli Studi di Cagliari-, Istituto di Clinica e Biologia dell' Eta Evolutive (Drs. Goddi and Cossu), Universitá degli Studi di Cagliari; and ktituto di Ricerca sulle Talassemie ed Anemie Mediterranee (Dr. Pirastu), CNR, Cagliari, Italy.

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 < 0.01, relative risk = 2.5) and DQw3 (p < 0.04, relative risk = 2.2). Using a ß-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 ß-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.

Address correspondence and reprint requests to Dr. Marrosu, Istituto di Neuropsichiatria Infantile, Via Ospedale 119,09124 Cagliari, Italy.

Supported in part by a grant from Regione Autonoma della Sardegna (legge 43 del 1950).

Received February 8, 1988. Accepted for publication in final form April 27, 1988.




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