Molecular Epidemiology Of Systemic Lupus Erythematosus

Objective To explore the relationship of SDF1-3'A,CCR2-64I and -2518MCP-1 polymorphisms with susceptibility of systemic lupus erythematosus and its clinical phenotype association, and to analyze gene-environmental and gene-gene interaction contributing to systemic lupus erythematosus.Methods Case-control study was used to explore the association between genes polymorphisms with susceptibility of systemic lupus erythematosus and its clinical phenotype association. Genomic DNA in the leukocyte was extracted by the phenol-trichloromethane extraction method. The polymorphisms of SDF1-3'A, -2518MCP-1 and CCR2-64I were determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and amplification refractory mutation system(ARMS) Respectively. The environmental factors for SLE were analyzed by univariate and multivariate unconditional logistic regression. The interaction between environmental factors and polymorphisms of SDF1-3'A, -2518MCP-1 and CCR2-64I contributing to systemic lupus erythematosus was also analyzed by logistic regressionmodel.Results There was no significant difference in distribution of allelic and genotype frequency of SDF1-3'A, -2518MCP-1 and CCR2-64I between patients with SLE and controls. The genotype frequency of -2518MCP-1A/G tended to increase incontrol,but the difference was not significant after being corrected (Pc=0.12). Theanalysis of gene-gene interaction showed that the GGAGGG genotype of control washigher than that of patients with SLE, however, no significant difference was found after being corrected(Pc= 1.00).Analysis on association between chemokinespolymorphisms and autoantibody indicated that no significant relationship was found. Compared with patients without arthritis, the -2518MCP-1G,A genotype frequency was higher in patients with arthritis(Pc=0. 018). It showed that the -2518MCP-1G,A genotype increased the risk of arthritis (OR=3.08,95%CI 1.27-7.57). There was no significant relationships between chemokines polymorphisms and IgG, IgA, IgM, C3, C4 level in serum, ESR, and disease activity of systemic lupus erythematosus. Nineteen factors were found to be associated with systemic lupus erythematosus with univariate unconditional logistic regression. But analyzed with multivariate unconditional logistic regression, only five factors left, in which drinking well water(OR=0.099) was protective factors for SLE , and drug allergy (OR=8.174), sunshine allergy (OR=18.339), taking antibiotics (OR=9.630) and oral contraceptives were risk factors for SLE. The analysis of unconditional logistic regression model showed there was interaction between eating irritable food and -2518MCP-1G,G genotype(OR=4.387).Conclusions There is no direct effect of SDF1-3'A,CCR2-64I and -2518MCP-1 polymorphisms on SLE ,but it is possible that the gene-gene interaction exists. -2518MCP-1 polymorphism may play an important role at onset of arthritis of patients with systemic lupus erythematosus. Many environmental factors are related to onset of systemic lupus erythematosus, and there is an interaction between ?2518MCP-1G,G genotype and eating irritable food.