Abstract

Relationship of CTLA-4 gene to latent autoimmune diabetes in adults and Type 2 diabetes: a population-based case-control study

Author(s): Xiuying Qi, Jing Wang, Zhongliang Xu, Jing Sun Lina Keller & Weili Xu

Aim: The influence of polymorphisms of the CTLA-4 gene on latent autoimmune diabetes in adults (LADA) and Type 2 diabetes mellitus (T2DM) remains unclear. We aimed to investigate the association of the 49A/G polymorphism in exon 1 of the CTLA-4 gene with LADA and T2DM.

Subjects & methods: This matched case–control study of 432 participants included 48 LADA cases, 192 patients with T2DM and 192 diabetesand prediabetes-free subjects as normal controls. LADA-normal control and LADA–T2DM control were 1:4 matched, and T2DM-normal control was 1:1 matched, based on age, sex and residence area. The 49A/G polymorphisms at exon 1 of the CTLA-4 gene were genotyped using PCR-RFLP. Data were analyzed using conditional logistic regression with adjustment for potential confounders.

Results: The frequencies of the G allele of CTLA-4 were 59.4% in LADA patients, 43.0% in T2DM cases and 21.9% in normal controls. In multiadjusted conditional logistic regression analysis, compared with CTLA-4 AA genotype, AG and GG led to odds ratios (95% CIs) of 16.82 (5.34–52.97) and 28.65 (7.06–116.34) for LADA, and 3.41 (2.17–5.37) and 3.57 (1.77–7.19) for T2DM, respectively. There was a joint effect of the G alelle of CTLA-4 and family history of diabetes on the occurrence of LADA and T2DM.

Conclusion: The polymorphisms of the CTLA-4 gene are associated with LADA and T2DM, and the effect of the G allele on LADA is stronger than on T2DM. The odds of LADA and T2DM may be additionally increased by the presence of family history of diabetes among people carrying the CTLA-4 G allele.