title: CTLA4+49G allele associates with early onset of type 1 diabetes in North Indians.
abstract: Type 1 diabetes (T1D) is a complex autoimmune disease with strong genetic influence. In this study, we investigated +49A/G SNP (rs 231775) in exon 1 of cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) by PCR-RFLP and its influence as a risk factor for the disease in the North Indian population. This polymorphism at codon 17 results in an amino acid substitution (Thr/Ala) in the leader peptide of the molecule. The study included 232 patients with T1D (age at onset of disease (AOD): 0.5-37 years) and 305 ethnically matched healthy controls. The DNA obtained from these 537 individuals was amplified using a set of specific primers followed by restriction enzyme digestion with Fnu4HI. The +49G allele as well as its homozygous genotype G/G was observed to be significantly higher in patients as compared to the healthy controls {(37.3% vs. 25.6%, P = 4.96E(-05) , OR = 1.73; 95%CI = 1.33-2.25) (15.52% vs. 6.6%, P = 0.001, OR = 2.62; 95% CI = 1.48-4.63) respectively}. The frequency of G/G genotype was significantly higher in patients with early age at onset of disease (AOD:<12 years) as compared to that in the late-onset patients with AOD: ≥12 years (21.1% vs. 10.6%, P = 0.042, OR = 2.26; 95% CI = 1.09-4.67) as well as to that in the healthy controls (21.1% vs. 6.6%, P = 0.00004, OR = 3.8; 95% CI = 2.01-7.2). Further analysis revealed that the median AOD significantly reduced (P = 0.049) from 14 years in patients with A/A genotype to 11 and 10 years in those with A/G and G/G genotypes, respectively. These results suggest that CTLA4+49G allele, particularly in homozygous G/G condition, associates with early onset of T1D.
authors.affiliation: Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: N
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: G
authors.identifier: http://orcid.org/0000-0002-1319-7012
authors.initials: G
authors.lastname: Kaur
authors.affiliation: Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: U
authors.initials: U
authors.lastname: Kanga
authors.affiliation: Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: N K
authors.initials: NK
authors.lastname: Mehra
authors.affiliation: Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: S C
authors.initials: SC
authors.lastname: Neolia
authors.affiliation: Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: N
authors.initials: N
authors.lastname: Tandon
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149, Hôpital Robert Debre, Université Paris Diderot, Paris, France.
authors.forename: S C
authors.initials: SC
authors.lastname: Zucman
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D060908:CTLA-4 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D060908:CTLA-4 Antigen