Associations of CTLA4 +49 A/G Dimorphism and HLA-DRB1*/DQB1* Alleles With Type 1 Diabetes from South India

  • Ravi Padma-Malini
  • Chinniah Rathika
  • Sivanadham Ramgopal
  • Vijayan Murali
  • Pannerselvam Dharmarajan
  • Subramanian Pushkala
  • Karuppiah Balakrishnan
Original Article


The aim of present study was to elucidate the association of CTLA4 +49 A/G and HLA-DRB1*/DQB1* gene polymorphism in south Indian T1DM patients. The patients and controls (n = 196 each) were enrolled for CTLA4 and HLA-DRB1*/DQB1* genotyping by RFLP/PCR-SSP methods. The increased frequencies of CTLA4 ‘AG’ (OR = 1.99; p = 0.001), ‘GG’ (OR = 3.94; p = 0.001) genotypes, and ‘G’ allele (OR = 2.42; p = 9.26 × 10−8) were observed in patients. Reduced frequencies of ‘AA’ (OR = 0.35; p = 7.19 × 10−7) and ‘A’ (OR = 0.41; p = 9.26 × 10−8) in patients revealed protective association. Among HLA-DRB1*/DQB1* alleles, DRB1*04 (OR = 3.29; p = 1.0 × 10−5), DRB1*03 (OR = 2.81; p = 1.9 × 10−6), DQB1*02:01 (OR = 2.93; p = 1.65 × 10−5), DQB1*02:02 (OR = 3.38; p = 0.0003), and DQB1*03:02 (OR = 7.72; p = 0.0003) were in susceptible association. Decreased frequencies of alleles, DRB1*15 (OR = 0.32; p = 2.55 × 10−7), DRB1*10 (OR = 0.45; p = 0.002), DQB1*06:01 (OR = 0.43; p = 0.0001), and DQB1*05:02 (OR = 0.28; p = 2.1 × 10−4) in patients were suggested protective association. The combination of DRB1*03+AG (OR = 5.21; p = 1.4 × 10−6), DRB1*04+AG (OR = 2.14; p = 0.053), DRB1*04+GG (OR = 5.21; p = 0.036), DQB1*02:01+AG (OR = 4.44; p = 3.6 × 10−5), DQB1*02:02+AG (OR = 20.9; p = 9.5 × 10−4), and DQB1*02:02+GG (OR = 4.06; p = 0.036) revealed susceptible association. However, the combination of DRB1*10+AA (OR = 0.35; p = 0.003), DRB1*15+AA (OR = 0.22; p = 5.3 × 10−7), DQB1*05:01+AA (OR = 0.45; p = 0.007), DQB1*05:02+AA (OR = 0.17; p = 1.7 × 10−4), DQB1*06:01+AA (OR = 0.40; p = 0.002), and DQB1*06:02+AG (OR = 0.34; p = 0.001) showed decreased frequency in patients, suggesting protective association. In conclusion, CTLA4/HLA-DR/DQ genotypic combinations revealed strong susceptible/protective association toward T1DM in south India. A female preponderance in disease associations was also documented.


T1DM HLA CTLA-4 Autoimmunity Polymorphism PCR–RFLP PCR-SSP 



The authors are thankful to the UGC-MRP ( (SR) dt: 11.07.2012), TTS-MKU, DBT-IPLS and the clinical lab technicians of Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India.

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflict of interest.

Ethical Approval

Madurai Kamaraj University and Madras Medical College, Chennai ethical committees were approved the present study.

Supplementary material

10528_2018_9856_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 14 kb)
10528_2018_9856_MOESM2_ESM.docx (15 kb)
Supplementary material 2 (DOCX 15 kb)
10528_2018_9856_MOESM3_ESM.docx (16 kb)
Supplementary material 3 (DOCX 15 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Ravi Padma-Malini
    • 1
  • Chinniah Rathika
    • 1
  • Sivanadham Ramgopal
    • 1
  • Vijayan Murali
    • 2
  • Pannerselvam Dharmarajan
    • 3
  • Subramanian Pushkala
    • 4
  • Karuppiah Balakrishnan
    • 1
  1. 1.Department of ImmunologyMadurai Kamaraj UniversityMaduraiIndia
  2. 2.Garrison Institute on AgingTexas Tech University Health Sciences CenterLubbockUSA
  3. 3.Department of DiabetologyRajiv Gandhi Government General HospitalChennaiIndia
  4. 4.Department of ImmunologyThe Tamil Nadu Dr. M.G.R. Medical UniversityChennaiIndia

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