Abstract
Autoimmune thyroid diseases (AITDs) are chronic organ-specific autoimmune diseases and mainly include Graves' disease (GD) and Hashimoto's thyroiditis (HT). CD14 is an important component of the immune system as a receptor for gram-negative lipopolysaccharide (LPS). The genetic polymorphisms of CD14 have been confirmed to be associated with a variety of autoimmune diseases. However, its relationship with AITDs is still unclear. The study was aimed to determine whether four single nucleotide polymorphisms (rs2915863, rs2569190, rs2569192, and rs2563298) of CD14 are associated with AITDs and its subgroups of GD and HT. The results showed significant association of rs2915863 and rs2569190 with GD. The frequencies of rs2915863 genotypes and T allele in patients with GD differed significantly from their controls (P = 0.007 and P = 0.021, respectively). For rs2569190, frequencies of genotypes and G allele in GD patients also showed positive P-values (P = 0.038 and P = 0.027, respectively). The correlations between these two loci and GD are more pronounced in female GD patients and patients with a family history. In genetic model analysis, the allele model, recessive model, and homozygous model of rs2569190 and rs2915863 embodied strong correlations with GD after the adjusting of age and gender (P = 0.014, P = 0.015, P = 0.009, and P = 0.014, P = 0.001, P = 0.006, respectively). However, these four sites are not related to HT. We firstly discovered the relationship between CD14 gene polymorphism and GD, and the results indicate that CD14 is an important risk locus for AITD and its SNPs may contribute to host's genetic predisposition to GD.
Highlights
Autoimmune thyroid diseases (AITDs) are chronic thyroid-specific autoimmune diseases and mainly include Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) [1]
We examined the frequency distribution for each allele and analyzed the association for each SNP in a case-control manner
There are no significant association between these four SNPs and AITDs, rs2915863 and rs2569190 are significantly correlated with GD
Summary
Autoimmune thyroid diseases (AITDs) are chronic thyroid-specific autoimmune diseases and mainly include Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) [1]. The specific pathogeny of AITDs is still unclear and may be related to genetic susceptibility, immunopathogenic mechanisms, and environmental factors [4, 5]. As a pattern recognition factor, CD14 protein is constitutively expressed in majority of innate immune response cells, and plays a central role in innate immunity through recognition of bacterial lipopolysaccharide (LPS) [6, 7]. Membrane CD14 is expressed primarily on the surface of monocytes, macrophages, and neutrophils, while sCD14 is predominantly in serum [8]. Detection of sCD14 in serum can partially reflect the expression of CD14 gene in vivo. As an important component of innate immunity, alterations in CD14 expression appear to correlate with aberrant immune responses and autoimmune diseases. This study was conducted to explore the association of four CD14 polymorphisms (rs2915863, rs2569190, rs2569192, and rs2563298) with the AITDs in the population of south China, and to explore its mechanisms though bioinformatics analysis
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