Heterogeneity at the HLA-DRB1 allelic variation locus does not influence multiple sclerosis disease severity, brain atrophy or cognition
Van der Walt, A and Stankovich, J and Bahlo, M and Taylor, BV and Van der Mei, IAF and Foote, SJ and Rubio, JP and Kilpatrick, TJ and Butzkueven, H, Heterogeneity at the HLA-DRB1 allelic variation locus does not influence multiple sclerosis disease severity, brain atrophy or cognition , Multiple Sclerosis, 17, (3) pp. 344-352. ISSN 1352-4585 (2011) [Refereed Article]
Background: HLA-DRB1*1501 (DR15) and other HLA class II alleles increase the risk of developing multiple sclerosis
(MS). However, the contribution of genetic heterogeneity to the clinical course of MS remains controversial. We
examined the influence of DR15 and other common DRB1 alleles (DRB1*01 (DR1), DRB1*03 (DR3) and DRB1*04
(DR4) on MS severity in a large, Australian, population-based cohort.
Methods: We studied the association between common HLA-DRB1 alleles and genotypes and age of onset as well as
three clinical disease severity descriptors: Multiple Sclerosis Severity Score, progression index), and the interval between
the first and second attack in 978 patients with relapsing remitting MS and secondary progressive MS. We assessed
cognition using the Symbol Digit Modalities Test in 811 patients and brain atrophy using the linear magnetic resonance
imaging marker, the intercaudate ratio, in 745 patients.
Results: Carrying DR15 significantly decreased the age of MS onset by 3.2 years in homozygotes and 1.3 years in
heterozygotes. Carrying the HLA-DR15, -DR1, -DR3 or -DR4 alone or in combination did not affect clinical disease
severity, cognition or cerebral atrophy.
Conclusions: This study confirms that heterogeneity of HLA-DRB1 does not influence disease outcome in relapsing MS
patients, with the exception of a younger age of onset in HLA-DR15 carriers.