CTLA4 +49G allele in combination with HLA-DR3 associates with type 1 diabetes as well as its onset in North Indians
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1
All India Institute of Medical Sciences, Dept. of Transplant Immunology & Immunogenetics, India
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2
All India Institute of Medical Sciences, Dept. of Endocrinology & Metabolism, India
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3
Institut National de la Santé et de la Recherche Médicale (INSERM),, France
Type 1 diabetes is a complex autoimmune disease with a strong genetic influence. We have investigated the role of the CTLA4 (Cytotoxic T-lymphocyte associated antigen -4) exon 1 A49G polymorphism and its role as a risk factor for T1D in the North Indian population. We studied 232 type 1 diabetic patients and 200 healthy controls by PCR amplification followed by restriction enzyme digestion with FnU4HI. Allele G at +49 position in codon1 of CTLA 4 gene was significantly increased in type 1 diabetic patients as compared to that in healthy controls (37.3% in patients vs 29% in controls, p= 0.012, OR=1.46, 95%CI= 1.09-1.94 ). Further, the frequency of homozygous GG genotype was significantly increased among patients than controls (15.5% vs 5.0%, p=0.001, OR=3.49 (95% CI=1.7-7.13)). The patients with younger age at onset of disease (<14 years) had a significantly high frequency of G positive genotypes (A/G or G/G) than those with an older age at onset of disease (≥14 years) (66% vs 47.1%, p=0.007, OR=2.18 (95%CI=1.27-3.76). Further analysis involving the HLA data revealed that the CTLA4 +49G allele is not in linkage disequilibrium with the reported susceptible HLA-DR3 allele, however the susceptibility conferred by +49G allele as well as its effect on the disease onset was observed to be dependent on the presence of HLA-DR3 allele. These results suggest that CTLA4 +49G allele in the presence of HLA-DR3 allele not only confers susceptibility to T1D and but is a strong marker for acceleration of disease development
Keywords:
type 1 diabetes,
CTLA-4,
HLA-DR3,
onset,
North Indians
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
KUMAR
N,
Kaur
G,
Kanga
U,
Tandon
N,
Zucman
SC and
Mehra
NK
(2013). CTLA4 +49G allele in combination with HLA-DR3 associates with type 1 diabetes as well as its onset in North Indians.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00566
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Received:
02 May 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. NEERAJ KUMAR, All India Institute of Medical Sciences, Dept. of Transplant Immunology & Immunogenetics, NEW DELHI, Delhi, India, neerajkaiims@hotmail.com