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HLA Class II Susceptibility to Multiple Sclerosis Among Ashkenazi and Non-Ashkenazi Jews
Oh Joong Kwon, PhD;
Arnon Karni, MD;
Shoshana Israel, PhD;
Chaim Brautbar, PhD;
Avraham Amar, PhD;
Zeev Meiner, MD;
Oded Abramsky, MD, PhD;
Dimitrios Karussis, MD, PhD
Arch Neurol. 1999;56:555-560.
Objective To look for HLA class II alleles and haplotypes conferring susceptibility to multiple sclerosis (MS) in the Jewish population of Israel.
Design Population-based cohort of clinically definite patients with MS tested prospectively over 7 years.
Setting Referral center in a neurology clinic at a university hospital in the greater Jerusalem area in Israel.
Patients A total of 162 consecutive patients with clinically definite MS from the 2 main ethnic Jewish groups in Israel: 104 Ashkenazi (80 with a relapsing remitting or secondary progressive and 24 with a primary chronic progressive course of the disease) and 58 non-Ashkenazi (36 with a relapsing remitting or secondary progressive course and 22 with a primary chronic progressive course of the disease), matched with 132 Ashkenazi and 120 non-Ashkenazi healthy controls.
Main Outcome Measures The relationship between the various HLA class II alleles and haplotypes and MS, as defined by the polymerase chain reaction and sequence-specific oligonucleotide probe hybridization, among the Ashkenazi and the non-Ashkenazi Jewish sections and with respect to the different clinical courses of the disease.
Results The haplotype DRB1*1501, DQA1*0102, DQB1*0602 was found to be associated with MS among both Ashkenazi and non-Ashkenazi patients (P<.001 and P=.04, respectively). Among the non-Ashkenazi patients, a new association of haplotypes DRB1*1303, DQA1*05, and DQB1*0301with MS was detected (P=.03). The MS susceptibility alleles, DRB1*1501, DQA1*0102, and DQB1*0602 , were found in association with the Ashkenazi patients (P<.001, P=.02, and P=.01, respectively); DRB1*1501 and DRB1*1303 were more frequently observed among the non-Ashkenazi patients (P=.03, P=.04, respectively). On subdivision of the patients into clinical subgroups, associations of DRB1*0801, DQA1*0102, DQA1*0401, and DQB1*0602 with primary chronic progressive MS among the Ashkenazi patients were evident (P=.03, P=.04, P=.04 and P=.05, respectively), whereas DRB1*1501, DRB1*03011, and DQB1*0602 were associated with relapsing remitting or secondary progressive among the non-Ashkenazi patients (P=.05, P=.05, and P=.03, respectively).
Conclusions This study, unlike previous ones, is the first to show a significant association between HLA class II alleles and MS in the Jewish population. The association with the HLA-DR2–related haplotype is similar to that among non-Jewish white patients with MS. Moreover, our data support the possibility that DRB1*1501 is the susceptibility allele responsible for the association between this haplotype and MS in the Jewish population. Our study also underscores differences in HLA profiles between Ashkenazi and non-Ashkenazi patients, and between the different clinical courses of the disease. The latter may indicate that the clinical courses of MS are influenced by the genetic background.
From the Tissue Typing Unit and the Lautenberg Center for General and Tumor Immunology (Drs Kwon, Israel, Brautbar, and Amar), and the Department of Neurology (Drs Karni, Meiner, Abramsky, and Karussis), Hadassah University Hospital, Hebrew University Hadassah Medical School, Jerusalem, Israel.
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