Role of CD160/HVEM/LIGHT/BTLA Signaling Pathway in Graves Disease

thyroid gland
Illustration of the thyroid gland.
Investigators say the discovery of the role of the CD160/HVEM/LIGHT/BTLA pathway in Graves disease adds new data to the genetic contribution to disease susceptibility.

The CD160 rs744877 polymorphism has been found to be associated with Graves disease, providing new insight into the genetic components contributing to the condition and further implicating the role of the CD160/HVEM/LIGHT/BTLA pathway in its pathogenesis, according to the result of a study were published in BMC Endocrine Disorders.

The study included 1017 patients with autoimmune thyroid disease, including 634 patients with Graves disease and 383 patients with Hashimoto thyroiditis. Another 856 unrelated participants without thyroid disease were recruited for the control group. High-throughput genotyping was used to detect CD160 single nucleotide polymorphisms (SNPs) in the study population.

The researchers found significant differences between patients with Graves disease vs the control group in regard to genotype distribution (P =.014) and allele frequency of rs744877 (P =.034). In contrast, there was no difference between patients with Hashimoto thyroiditis and the control group for genotype distribution (P =.464) and allele frequencies of rs744877 (P =.593).

Under a dominant model for CC/AC vs AA, there was a significant association between CD160 rs744877 and autoimmune thyroid disease in a multivariate logistic regression analysis adjusted for age and sex (odds ratio [OR], 0.78; 95% CI, 0.65-0.95; P =.011). There was also a significant association between CD160 rs744877 and autoimmune thyroid disease under an additive model for AC vs AA (OR, 0.76; 95% CI, 0.63-0.93; P =.007). 

In addition, the researchers found a significant association between rs744877 with Graves disease under an allele model for C vs A (OR, 0.84; 95% CI, 0.71-0.98; P =.027), a dominant model for CC/AC vs AA (OR, 0.74; 95% CI, 0.60-0.92; P =.005), and an additive model for AC vs AA (OR, 0.72; 95% CI, 0.58-0.90, P =.004).

While this study suggests CD160 rs744877 locus is a susceptible factor for Graves disease, the researchers note that the findings did not uncover the molecular mechanisms underlying CD160 rs744877 in its role in autoimmune diseases.

The researchers added that the “findings in our study still need to be validated in future studies, especially for those from other countries or populations.”

Reference

He W, Zhao J, Liu X, et al. Associations between CD160 polymorphisms and autoimmune thyroid disease: a case-control study. BMC Endocr Disord. 2021;21(1):148. doi:10.1186/s12902-021-00810-w