Abstract
Autoimmune hypothyroidism is known to be caused by immune responses related to the thyroid gland and its immunological feature includes presence of autoimmune antibodies. Therefore the aim was to analyze presence of anti-TPO antibodies in hypothyroidism patients in Gujarat. Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) is one of the susceptibility genes for various autoimmune diseases. Hence, exon1 +49A/G and 3’UTR CT60A/G single nucleotide polymorphisms (SNPs) in CTLA4 and its mRNA expression levels were investigated in autoimmune hypothyroidism patients. Thyroglobulin (TG) is known to be associated with autoimmune thyroid disorders and thus exon 33 (E33) SNP in TG was investigated. We analyzed the presence of anti-TPO antibodies in the plasma samples of 84 hypothyroidism patients and 62 controls by ELISA. PCR-RFLP technique was used for genotyping of polymorphisms. sCTLA4 and flCTLA4 mRNA expression levels were assessed by real time PCR. 59.52% of hypothyroid patients had anti-TPO antibodies in their circulation. The genotype and allele frequencies differed significantly for +49A/G (p = 0.0004 for +49AG, p = 0.0019 for +49GG & p = 0.0004 for allele), CT60 (p = 0.0110 for CT60AG, p = 0.0005 for CT60GG & p<0.0001 for allele) and TG E33 (p = 0.0003 for E33TC p<0.0001 for E33CC& p<0.0001 for allele) SNPs between patients and controls. Patients had significantly decreased mRNA levels of both sCTLA4 (p = 0.0017) and flCTLA4 (p<0.0001) compared to controls. +49A/G and CT60 polymorphisms of CTLA4 were in moderate linkage disequilibrium. Logistic regression analysis indicated significant association of CT49A/G, CT60A/G and TG exon 33 polymorphisms with susceptibility to autoimmune hypothyroidism when adjusted for age and gender. Our results suggest +49A/G and CT60 polymorphism of CTLA4 and E33 polymorphism of TG may be genetic risk factors for autoimmune hypothyroidism susceptibility and down regulation of both forms of CTLA4 advocates the crucial role of CTLA4 in pathogenesis of autoimmune hypothyroidism.
Highlights
Hypothyroidism is an endocrine disorder characterized by decreased activity of thyroid gland leading to insufficient production of thyroid hormones
It was found that 59.52% (n = 50) of hypothyroidism patients (n = 84) had anti-TPO antibodies in their blood circulation suggesting that autoimmunity may play an important role in the pathogenesis of the disease these autoimmune hypothyroidism patients had significantly increased anti-TPO antibody levels as compared to controls (p
Analysis of the mRNA expression of full length CTLA4 (flCTLA4) and soluble CTLA4 (sCTLA4) based on the +49A/G and CT60A/ G genotypes of 45 autoimmune hypothyroidism patients and 60 controls was performed
Summary
Hypothyroidism is an endocrine disorder characterized by decreased activity of thyroid gland leading to insufficient production of thyroid hormones. There remains elevated thyrotropin but decreased thyroid hormones serum levels in case of overt or clinical hypothyroidism [1] [2]. A large, cross-sectional, comprehensive study recently carried out in adult population across the country, indicates about 10.9% prevalence of hypothyroidism [11]; whereas, the prevalence of hypothyroidism in the developed countries is about 4–5% [12, 13]. This indicates even though most of the regions of India have been made iodine sufficient there is still high prevalence of hypothyroidism. Clinical investigation of patients in India does not include evaluation of thyroid autoantibodies and iodine deficiency is believed to be the sole candidate for hypothyroidism pathogenesis which may not be the case
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