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  • Title: Association of CD40 polymorphisms and haplotype with risk of systemic lupus erythematosus.
    Author: Wu CJ, Guo J, Luo HC, Wei CD, Wang CF, Lan Y, Wei YS.
    Journal: Rheumatol Int; 2016 Jan; 36(1):45-52. PubMed ID: 26289938.
    Abstract:
    Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that is caused by genetic and environmental factors. Current evidence shows that the CD40-CD40L system plays a crucial role in the development, progression and outcome of SLE. CD40, which stimulates lymphocyte proliferation and differentiation, is an important immunomodulator and is expressed in the thyroid follicular cells as well as antigen-presenting cells. The aim of the present study was to investigate whether CD40 gene polymorphism confers susceptibility to SLE and its impact on CD40 expression in Chinese. We analyzed four single nucleotide polymorphisms of CD40 gene rs1883832C/T, rs13040307C/T, rs752118C/T, and rs3765459G/A in 205 patients with SLE and 220 age- and sex-matched controls, using Snapshot SNP genotyping assays and DNA sequencing method. Soluble CD40 (sCD40) levels were measured by ELISA. There were significant differences in the genotype and allele frequencies of CD40 gene rs1883832 C/T polymorphism between the group of patients with SLE and the control group (P < 0.05). sCD40 levels were increased in patients with SLE compared with controls (P < 0.01). Moreover, genotypes carrying the CD40 rs1883832 T variant allele were associated with increased CD40 levels compared with the homozygous wild-type genotype in patients with SLE. The rs1883832 C/T polymorphism of CD40 and its sCD40 levels were associated with SLE in the Chinese population. These data suggest that CD40 gene may play an essential role in the development of SLE.
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