Synergistic interactions of Angiotensin Converting Enzyme (ACE) gene and Apolipoprotein E (APOE) gene polymorphisms with T1DM susceptibility in south India

Type 1 diabetes mellitus (T1DM) is an autoimmune endocrine disease, in which both gene-gene and gene-environmental factors play a key role in the development and progression of the disease. The main aim of the present study was to determine the association of Angiotensin Converting Enzyme (ACE) and Apolipoprotein E (APOE) gene polymorphisms in T1DM patients. A cohort of 196 T1DM patients (n = 196) and age/sex matched controls (n = 196) were enrolled for typing of ACE and APOE by PCR-SSP and PCR-RFLP methods. We observed an increased frequencies of 'DD' (P: OR = 2.40; M: OR = 2.08 and F: OR = 2.90), 'ID' (P: OR = 1.94; M: OR = 2.01; F: OR = 1.84) genotypes and 'D' allele (P: OR = 2.43; M: OR = 2.21; F: OR = 2.74) in patients confirmed their susceptible association. Whereas, the 'II' genotype (P: OR = 0.25; M: OR = 0.28; F: OR = 0.21) and 'I' allele frequencies (P: OR = 0.41; M: OR = 0.45; F: OR = 0.36) were decreased in patients suggested their protective association. Multivariate analysis revealed that the 'GAD65(+)', 'IA2(+)' and 'GAD65(+) + IA2(+)' auto-antibodies were significantly associated with patients. Genetic model of inheritance analysis showed that, the additive (P: OR = 5.15; M: OR = 5.52; F: OR = 4.66), recessive (P: OR = 2.40; M: OR = 2.41; F: OR = 2.41), dominant (P: OR = 3.99; M: OR = 4.79; F: OR = 3.21) and co-dominant (P: OR = 1.94; M: OR = 2.60) models were significantly associated in patients. No significant association was observed for the APOE genotypes with T1DM. However, 'epsilon 3' allele (M: OR = 0.191; F: OR = 0.128) was decreased in patients confirming its moderate protection. Analysis on synergistic association have revealed that: 'DD + epsilon 3/epsilon 4' (P: OR = 11.59) and 'ID + epsilon 3/epsilon 3' (P: OR = 1.66) were susceptible; and 'II + epsilon 3/epsilon 3' (P: OR = 0.25) as the protective combinations. Thus, the present study conclude the stronger susceptible risks for the combinations 'DD' + 'epsilon 3/epsilon 4' and 'ID' + 'epsilon 3/epsilon 3' towards the development of T1D in south India.