Association of MICA and CTLA-4 gene polymorphisms with the risk of autoimmune thyroid diseases in children with type 1 diabetes

CTLA-4 and MICA are common candidate genes for type 1 diabetes (T1D) and autoimmune thyroid diseases (AITD). The data concerning the association of CT60 (+6230G>A) (rs3087243) polymorphism within the CTLA-4 gene and the short tandem repeats (STR) in exon 5 of the MICA gene with autoimmune endocrinopathies are distinct in different populations. This work was aimed to reveal the alleles and genotypes associated with a predisposition to AITD in children with T1D in Belarus.

We investigated the allele and genotype frequencies of CTLA-4 rs3087243 and the STR in exon 5 of MICA in children diagnosed with autoimmune polyglandular syndrome (APS) type 3a (n = 52), T1D (n = 95) and control group (n = 40).

A comparative analysis of the genotype distribution of CTLA-4 rs3087243 polymorphism showed that children with APS type 3a were significantly more likely to have the GG genotype compared with patients with T1D (OR = 5.06 (1.12–22.97)) and the control group (OR = 5.30 (1.04–27.12)). It was found that MICA-A5.1/5.1 genotype is associated with an increased risk of the combined development of T1D and AITD (OR = 3.65 (1.10‒12.05)). We revealed the association of the MICA-A9 allele with a predisposition to APS type 3a in girls with T1D (OR = 2.60 (1.17‒5.74)), especially with the most severe thyroid pathology: overt hypothyroidism (OR = 6.42 (1.70‒24.24)) and thyroid hypertrophy (OR = 7.78 (1.81‒33.38)).

The obtained data identify the GG genotype at rs3087243 (CTLA-4) as a risk factor for APS type 3a in children  with T1D; and the MICA-A9 allele – for AITD with overt hypothyroidism and goiter in girls with T1D.

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