title: Association of HLA-A, B, DRB1* and DQB1* alleles and haplotypes in south Indian T2DM patients.
abstract: The genes of Human Leukocyte Antigen (HLA) system are implicated in the susceptibility of several diseases including Type 2 diabetes (T2DM). Therefore, we aimed to investigate the association of HLA alleles with T2DM in south India. A total of 344 patients (195 males; 149 females) and 309 controls (186 males; 123 females) were genotyped for HLA-DR/-DQ alleles. Based on predominant DR/DQ haplotypes, 222 patients and 222 age/sex matched controls were HLA-A/-B genotyped. HLA alleles were typed by PCR-SSP methods. Susceptible association was observed for the alleles A*33 (OR=13.8), A*01 (OR=3.69), A*02 (OR=2.91), B*07 (OR=4.12), DRB1*11 (OR=2.23), DRB1*04 (OR=1.51), DRB1*03 (OR=1.90) and DQB1*02 (OR=1.49). Protective association was observed for the alleles A*11 (OR=0.59), A*68 (OR=0.68), B*40 (OR=0.50), B*54 (OR=0.42), B*57 (OR=0.31), B*51 (OR=0.29) and DRB1*10 (OR=0.45). Gender stratified analysis too confirmed many of these associations. Predominant susceptible haplotypes were A*33-B*40 (OR=10.27), A*01-B*07 (OR=4.97), A*02-B*07 (OR=6.50), DRB1*03-DQB1*05 (OR=1.88), DRB1*03-DQB1*06 (OR=3.01), DRB1*04-DQB1*05 (2.63), A*01-B*07-DRB1*10 (OR=8.26) and A*11-B*35-DRB1*07 (OR=9.338). Haplotypes A*03-B*07 (OR=0.57; p<0.034) and DRB1*10-DQB1*05 (OR=0.57; p<0.033) were protectively associated. Further, a very strong susceptible association was documented for four-locus haplotypes such as A*11-B*40-DRB1*15-DQB1*06 (n=15; OR=16.01; p<0.001); A*01-B*07-DRB1*10-DQB1*05 (n=8; OR=8.26; p<0.043) and A*11-B*07-DRB1*07-DQB1*05 (n=8; OR=8.26; p<0.043). Thus, a number of HLA alleles and haplotypes showed susceptible and protective association(s) in T2DM patients from south India.
authors: Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai - 625 021, Tamil Nadu, India.
authors: Rathika
authors: R
authors: Chinniah
authors: Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai - 625 021, Tamil Nadu, India; Department of Biotechnology & Genetic Engineering, School of Biotechnology, Bharathidasan University, Tiruchirappalli - 620 024, Tamil Nadu, India.
authors: Murali
authors: M
authors: Vijayan
authors: Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai - 625 021, Tamil Nadu, India.
authors: Ramgopal
authors: R
authors: Sivanadham
authors: Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai - 625 021, Tamil Nadu, India.
authors: Padma Malini
authors: PM
authors: Ravi
authors: Rajiv Gandhi Government General Hospital, Chennai-600 003, Tamil Nadu, India.
authors: Dharmarajan
authors: D
authors: Panneerselvam
authors: Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai - 625 021, Tamil Nadu, India. Electronic address: immunobala@mkuniversity.org.
authors: Balakrishnan
authors: B
authors: Karuppiah
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains
keywords: Alleles; DQB1*; DRB1*; HLA; Haplotypes; Type 2 diabetes