Gene-environment Interaction Of Gene Mutation And Environmental Factors On Systemic Lupus Erythematosus

Gene-environment interaction of gene mutation and environmental factors on systemic lupus erythematosus.Objective To evaluate the effect of interaction of RANTES' two SNPs and CCR5 mutation and environmental factors on systemic lupus erythematosus, and to study the relationship of RANTES' two SNPs and CCR5 mutation with clinical feature and autoantibodies of systemic lupus erythematosus.Methods Genotypes of RANTES and CCR5 were determined by PCR-RFLP. The relationship of RANTES and CCR5 with clinical feature and autoantibodies of SLE was analyzed by X2 test in case-control study. The environmental factors for SLE, the interaction between environmental factors and RANTES and CCR5 were analyzed by univariate and multivariate unconditional logistic regressioaRes lts The genotyping frequencies of RANTES-403G/G G/A and A/A in patients with SLE were 76.71%, 21.92% and 1.37%, while those of RANTES-403G/G, G/A and A/A in control were 67.30%, 29.56% and 3.14%, respectively( P>0.05). The genotyping frequencies of RANTES-28C/C, C/G and G/G in patients with SLE were 76.71%, 21.92% and 1.37%, respectively, which were not significantly different from those in controls of 67.30%, 29.56% and 3.14% (P>0.05). The frequency of mutation CCR5A32 was 0 in patients with SLE and 0.3% in controls, which was no significant difference (P>0.05). The frequence of RANTES-403G/G compounded with 28C/C and CCR5/CCR5 was significantly different between SLE and control (72.6% vs 58.5% , P<0.05, OR=1.88). Four ultimate environmental factors were related with systemic lupus erylhematosus with multivariate unconditional logistic regression model, in which long-term using contraceptives, history of allergy and using antibiotic were risk factors for SLE, while drinking well water were protective factor for SLE. There were interactions between RANTES403G/A genotype and drinking well water. In theclinical aspect, there was no significant difference in means of ESR, IgG, IgA, IgM, C3, C4 and SLEDAI among different RANTES-403 locus and RANTES-28 locus genotypes (P>0.05). RANTES403 locus and RANTES28 locus mutation were not influential factors of anti-dsDNA antibody and anti-Sin antibody. Freqence of the mutation allele RANTES-403 A in renal damage group was lower than that of non-renal damage group and of control (1.49% vs 15.62%, 1.49% vs 17.9%, P<0.05) .There were no significant difference in freqence of the mutation allele RANTES-28C and CCR5A32 among renal damage group, non-renal damage group and control (P>0.05).Conclusions These results indicate that the SNPs of RANTES promoter and mutation of CCR5A32 have nothing to do with SLE. However, interaction of RANTES' two SNPs and CCR5 is related with SLE. Results also indicated there are gene-gene interaction among RANTES two SNPs and CCR5 mutation, and gene-environmental interaction of some environmental risk factors and RANTES for systemic lupus erythematosus. RANTES403 locus and RANTES28 locus mutation are not influential factors of anti-dsDNA antibody and anti-Sm antibody. RANTES-403 A is probably related with renal damage of SLE.