Autoimmune thyroid patients with CTLA-4 (+49A/G) GG/AG genotypes have high seropositivity to thyroid peroxidase than thyroglobulin

Abstract

Despite increasing burden of autoimmune thyroid disease (AITD) in India, there is paucity of data for the genetic susceptibility in Indian population which represents an important aspect to uncover the genetic factors for the cause or progression of different forms of AITD. It is known that production of auto-antibodies to thyroglobulin (TG) and thyroid peroxidase (TPO) is a characteristic feature of AITD. Production of high titres of auto-antibodies against TG and TPO is one the hallmarks of AITD that often precedes the development of clinical disease. The gene coding for cytotoxic T lymphocyte antigen-4 (CTLA-4) is considered an important candidate gene for susceptibility to AITD and also determines seropositivity. Earlier studies have demonstrated that polymorphic variants in CTLA-4 gene are linked to determine seropositivity. Hence, this study investigates a relationship between CTLA-4 (+49A/G) genotypes and seropositivity to anti-TPO and anti-TG antibodies in AITD patients. A total of 85 Indian participants were included and genotyped for CTLA-4 (+49A/G) single nucleotide polymorphism and further analyzed for seropositivity of TPO and TG auto-antibodies in mean age group of 35.76 ± 12.42 years of both the genders. The TPO seropositivity was reported higher in G allele containing genotypes GG and AG (66.66% and 58%, respectively) compared to AA (44.8%) genotype. Whereas, TG auto-antibodies showed highest seropositivity for genotype AA (55.17%) compared to AG (36%) and GG (16.6%). Higher median titre values were observed for TPO antibodies with GG genotype (1587.461 U/mL). In contrast to this, higher titres of auto-antibodies to TG were observed for individuals with AA genotype (520.746 U/mL). In conclusion, this study demonstrates a relationship between CTLA4 (+49A/G) genotype and seropositivity to thyroid auto antigens TPO and TG in Indian patients with clinical manifestation of Hashimoto's thyroiditis and Graves' disease, two different forms of AITD.