The H159Y Variant of the BAFF-R Gene (TNFRSF13C) Is Unrelated to the Risk of Developing Systemic Lupus Erythematosus and Sjögren's Disease in a Mexican Population

BAFF-R基因(TNFRSF13C)的H159Y变异与墨西哥人群罹患系统性红斑狼疮和干燥综合征的风险无关。

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Abstract

Systemic Lupus Erythematosus (SLE) and primary Sjögren's Disease (SjD) are autoimmune diseases characterized by the presence of autoantibodies that lead to damage in healthy tissues. The production of autoantibodies requires the activation and differentiation of B-lymphocytes into plasma cells. To achieve this effect, BAFF (B-lymphocyte activating factor), APRIL (A proliferation-inducing ligand), and their receptors are key factors. BAFF is a cytokine recognized by BAFF-R (BAFF receptor), which is increased and related to disease activity in both SLE and SjD patients. The H159Y mutation (rs61756766) in the gene encoding the BAFF-R, TNFRSF13C (Tumor Necrosis Factor Receptor Superfamily) has been shown in vitro to cause receptor hyperactivation via the NF-κB2 pathway. This study evaluated the frequency of this variant in a western Mexican population and its association with the risk of developing SLE and SjD. Genotypes of the TNFRSF13C H159Y (rs61756766) variant were determined by PCR-RFLP assay. sBAFF levels were measured by ELISA. The study included 300 SLE patients, 110 SjD patients, and 300 healthy subjects (HS). HS were in Hardy-Weinberg equilibrium. The data distribution was assessed using the Kolmogorov-Smirnov test. Group comparisons were conducted using the Chi-square test, Fisher's exact test, or the Mann-Whitney U test, as appropriate. A p-value of <0.05 was considered statistically significant. In the Mexican population, allelic and genotypic distribution frequencies of the H159Y variant (rs61756766) were similar between SLE patients and HSs, while the variant was not found in SjD patients. SLE patients carrying the heterozygous CT genotype showed a trend toward higher soluble BAFF (sBAFF) levels than wild-type genotype patients. This variant does not confer risk to SLE or SjD in the Mexican population. However, the heterozygous genotype may be associated with high levels of sBAFF in SLE patients.

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