Analysis of Associations of Human BAFF Gene Polymorphisms with Autoimmune Thyroid Diseases

Abstract

Background: The B-lymphocyte-activating factor (BAFF) is associated with B-cell functions, and gene polymorphisms of the BAFF have been linked to autoimmune diseases (AIDs). In this study, we explored possible associations of two BAFF single-nucleotide polymorphisms (SNPs), rs1041569 and rs2893321, with autoimmune thyroid diseases (AITDs) in an ethnic Chinese population.

Material and methods: In total, 319 Graves' disease (GD), 83 Hashimoto's thyroiditis (HT) patients, and 369 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism and direct sequencing were used to genotype rs2893321 and rs1041569.

Results: There was a significant difference in frequencies of the G allele and AG+GG genotype of rs2893321 between the GD and control groups (p = 0.013, odds ratio (OR) = 0.76, and p = 0.017, OR = 0.68, respectively) and between the AITD and control groups (p = 0.009, OR = 0.76, and, p = 0.014, OR = 0.69, respectively). The AA genotype of rs2893321 was associated with low titers of the thyroid-stimulating hormone receptor antibody (TSHRAb) (p = 0.015) in males but not in females. The AA genotype of rs2893321 was associated with the presence of two different types of thyroid autoantibody (TAb) (TSHRAb and Hashimoto's autoantibody (anti-thyroglobulin or anti-microsomal antibody)) in females and with that of one type in males.

Conclusions: rs2893321 may be a susceptible genetic variant for the development of GD and AITDs. Associations of rs2893321 with susceptibility to GD and AITDs and the correlation between rs2893321 and TAb exhibit a dimorphic pattern. Additional studies with larger sample sizes are required to confirm our findings.

Fig 1

Thyroid-stimulating hormone (TSH) receptor antibody titers at the baseline in different genotypes of rs1041569 (Panel A) and rs2893321 (Panel B) in Graves’ disease in females and males. TSHRAb, thyroid-stimulating hormone receptor antibody; the number in the column indicates the number of patients.

Fig 2

Anti-microsomal antibody (AmiA) titers at the baseline in different genotypes of rs1041569 (Panel A) and rs2893321 (Panel B) in autoimmune thyroid disease in females and males. Low AmiA, low AmiA titer; High AmiA, high AmiA titer; the number in the parenthesis indicates the number of patients; the number in the column indicates the frequency of the genotype.

Fig 3

Prevalence of different genotypes of rs1041569 (Panel A) and rs2893321 (Panel B) in existing types of thyroid autoantibody in autoimmune thyroid disease in females and males. 1A, Grave’s disease but without the anti-thyroglobulin and anti-microsomal antibody or those with Hashimoto’s thyroiditis (one type of antibody); 2A, Graves’ disease with either the anti-thyroglobulin or antimicrosomal antibody or both (two types of antibody); the number in the parenthesis indicates the number of patients; the number in the column indicates the frequency of the genotype.