Vitamin D status and vitamin D receptor (VDR) gene polymorphism (FokI rs2228570) in patients with autoimmune hypothyroidism

Abstract

Background: Autoimmune hypothyroidism is one of the most common causes of hypothyroidism, and vitamin D insufficiency has been linked to autoimmune diseases including autoimmune hypothyroidism, but its interplay with vitamin D receptor (VDR) gene variation remains poorly defined in the Bangladeshi population.

Objectives: To investigate vitamin D status in Bangladeshi patients with newly detected autoimmune hypothyroidism and examine its association with the VDR FokI gene polymorphism (rs2228570).

Methods: This Case-control study was conducted in the Department of Endocrinology, BMU, enrolling 135 patients with autoimmune hypothyroidism and 135 age- and sex-comparable euthyroid controls by non-random purposive sampling. Serum FT4, TSH, anti-TPO and anti-Tg antibodies were measured by chemiluminescence, 25-OH-vitamin D3 by HPLC-UV, and VDR FokI genotyped from whole blood. Data were analyzed using chi-square, Fisher's exact, Mann-Whitney U, Spearman correlation, and logistic regression under codominant, recessive, over-dominant, and log-additive genetic models, along with multivariable logistic regression.

Results: Vitamin D deficiency (14.81% vs 2.96%) and insufficiency (24.44% vs 8.89%) were significantly more common among cases than controls (p<0.001), and vitamin D correlated inversely with TSH, anti-TPO and anti-Tg, and positively with FT4 (all p<0.05). The TC genotype was most frequent in both groups; under the dominant model, T-allele carriage (TC+TT vs CC) was significantly associated with autoimmune hypothyroidism (OR=1.809, 95% CI 1.059-3.126, p=0.031), the best-fitting genetic model tested. However, vitamin D status did not differ across genotypes. On multivariable analysis, the CC genotype was independently protective (AOR=0.35, p=0.010), while family history of thyroid disease (AOR=11.45, p<0.001), obesity (AOR=3.77, p=0.008) and vitamin D deficiency (AOR=4.47, p=0.060) were the strongest independent predictors of autoimmune hypothyroidism.

Conclusions: Vitamin D deficiency/insufficiency and VDR FokI T-allele carriage were significantly associated with autoimmune hypothyroidism, with the CC genotype independently protective and family history and obesity as key co-predictors. These findings support a model in which vitamin D status and VDR-mediated immune signaling act as partially independent, clinically important contributors to autoimmune hypothyroidism in this population.

[J Assoc Clin Endocrinol Diabetol Bangladesh, 2026;5(Suppl 1): S36]