HLA associations in South Asian multiple sclerosis.
BACKGROUND
Previous efforts to identify Human Leukocyte Antigen (HLA) gene associations with multiple sclerosis (MS) in the South Asian population have been underpowered.


OBJECTIVE
To identify the primary HLA class II alleles associated with MS in Indians.


METHODS
We typed HLA-DRB1, -DQA1 and -DQB1 in 419 patients and 451 unrelated controls by polymerase chain reaction using sequence specific oligonucleotide probes (PCR-SSOP).


RESULTS
At the gene level DRB1 showed significant evidence of association (p=0.0000012), DQA1 showed only marginal evidence of association (p=0.04) and there was no evidence for association at DQB1 (p=0.26). At the DRB1 locus association is confirmed with the *15:01 (p=0.00002) and the *03 (p=0.00005) alleles.


CONCLUSIONS
Our study confirms that the risk effects attributable to the HLA- DRB1*15:01and DRB1*03 alleles seen in Europeans are also seen in Indians. The absence of any evidence of association with DQB1 alleles reflects the lower linkage disequilibrium between DQB1 alleles and DRB1 risk alleles present in this population, and illustrates the potential value of fine mapping signals of association in different ethnic groups.
Center for Advanced Neurological Research, KS Hegde Medical College, Nitte University, Mangalore, Karnataka, India panditmng@gmail.com.
Lekha
L
Pandit
Center for Advanced Neurological Research, KS Hegde Medical College, Nitte University, Mangalore, Karnataka, India.
Chaithra
C
Malli
Bombay Hospital and Research Center, Mumbai, India.
Bhim
B
Singhal
Medical Research Council Biostatistics Unit, Cambridge, UK.
James
J
Wason
Division of Brain Sciences, Imperial College London, UK.
Omar
O
Malik
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Stephen
S
Sawcer
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Maria
M
Ban
Center for Advanced Neurological Research, KS Hegde Medical College, Nitte University, Mangalore, Karnataka, India.
Anitha
A
D'Cunha
Center for Advanced Neurological Research, KS Hegde Medical College, Nitte University, Mangalore, Karnataka, India.
Sharik
S
Mustafa
D000328:Adult; D005260:Female; D056726:Genetic Association Studies; D059848:HLA-DQ alpha-Chains / Q000235:genetics*; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012042:Registries; D017422:Sequence Analysis, DNA
D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D059811:HLA-DRB1 Chains
HLA; South Asians; multiple sclerosis