Two HLA class I genes independently associated with multiple sclerosis.
OBJECTIVE
The risk of multiple sclerosis (MS) is influenced by HLA-DRB1, while protective effects have been proposed for HLA-A*02 and HLA-C*05. Our aim was to further understand the role of HLA class I in MS through a comprehensive investigation.


METHODS
1529 MS patients and 1814 controls from Sweden and Norway were genotyped for HLA-DRB1, HLA-A, and HLA-C. Simultaneous analysis of all alleles while adjusting for confounding was achieved using logistic regression.


RESULTS
We observed independent effects of all three genes. We confirm the HLA-A*02 (OR=0.73, p=9.2 x 10(-4)) association and report a novel effect of HLA-C*08 (OR=1.85, p=0.0093).


CONCLUSIONS
The HLA class I region contains two factors modulating MS risk, characterized by independent associations with HLA-A and HLA-C.
Link
Jenny
J
Karolinska Institutet, Department of Clinical Neuroscience, CMM L8:00, SE-17176 Stockholm, Sweden. jenny.link@ki.se
Lorentzen
Aslaug R
AR
Kockum
Ingrid
I
Duvefelt
Kristina
K
Lie
Benedicte A
BA
Celius
Elisabeth G
EG
Harbo
Hanne F
HF
Hillert
Jan
J
Brynedal
Boel
B
D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D015789:HLA-A2 Antigen / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D009664:Norway; D012307:Risk Factors; D013548:Sweden
D015789:HLA-A2 Antigen; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains