rs3806265 and rs4612666 of the NLRP3 Gene Are Associated With the Titer of Glutamic Acid Decarboxylase Antibody in Type 1 Diabetes

Abstract

Background and aims: The NLRP3 gene is reportedly associated with several autoimmune diseases. However, in the Chinese Han population, whether NLRP3 polymorphisms are associated with type 1 diabetes (T1D) is unclear. Therefore, this study examined the associations of rs3806265 and rs4612666 of the NLRP3 gene with T1D susceptibility and the clinical characteristics of Chinese Han T1D patients.

Methods: In total, 510 classic T1D patients and 531 healthy controls from the Chinese Han population were recruited for a case-control study. rs3806265 and rs4612666 of the NLRP3 gene were genotyped by MassARRAY. Logistic regression analysis and the chi-square test were used to compare the distributions of the alleles and genotypes of rs3806265 and rs4612666. The relationships between rs3806265 and rs4612666 and the clinical characteristics of T1D patients were analyzed by Kruskal-Wallis one-way ANOVA. Student's t test was used to analyze normally distributed data. Bonferroni correction was used for multiple comparisons.

Results: 1) rs3806265 was associated with glutamic acid decarboxylase antibody (GADA) titers (P = 0.02), and patients with the CC genotype had higher GADA titers than patients with the TT genotype. 2) rs4612666 was also associated with GADA titers (P=0.041). Compared with patients with the CC genotype, patients with the TT genotype had higher GADA titers. 3) rs3806265 and rs4612666 of the NLRP3 gene were not significantly associated with T1D susceptibility under different genetic models.

Conclusion: rs3806265 and rs4612666 of the NLRP3 gene were significantly associated with GADA titers in Chinese Han T1D patients.

Keywords: correlation analysis; glutamic acid decarboxylase antibody; inflammasome; single nucleotide polymorphism; type 1 diabetes.