Clinical Molecular Epidemiology Of Systemic Lupus Erythematosus

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the systemic organ damages.The cause of SLE is not yet very clarified. After the publication of the entire human genome, it is believed that SLE is caused by a complex interplay between various genetic and environmental factors. FcyRIIIA, CD24and CYP2C19*2play a major role in the pathogenesis,course and treatment of SLE. But the polymorphisms of these genes have not been widely studied.Objective:To study the frequencies of FcyRIIIA, CD24and CYP2C19*2polymorphisms in Chinese population and the potential role of these single nucleotide polymorphisms(SNPs) in SLE and lupus nephritis(LN). Methods:We studied324unrelated Chinese SLE patients and319controls. FcyRIIIA F158V polymorphism was genotyped by specific primer-polymerase chain reaction(PCR). CD24A57V、CYP2C19*2polymorphism were genotyped by PCR and restriction fragment length polymorphism(RFLP).Results:1. The observed frequency of F allele of FcyRIIIA polymorphism is60.8%in Chinese population. FcyRIIIA polymorphism revealed a significant difference of both genotype and allele distribution between SLE patients and controls. LN patients have a significant decrease in carrier frequency of the V-allele, while the carrier frequency of the F-allele reveals a significant difference between the patients of different course of LN.2. The observed frequency of T allele of CD24polymorphism is34.8%in Chinese people. CD24polymorphism revealed a significant difference in SLE patients and controls, which suggests T allele of CD24might be a risk factor for SLE. There is no significant difference of both genotype and aileie distribution of CD24polymorphism in neuropsychiatric lupus erythematosus(NPLE) patients and other SLE patients.3. The observed frequency of A allele of CYP2C19*2polymorphism is29.9%in Chinese population. Patients who were either heterozygous or homozygous for CYP2C19*2had a significantly lower risk of ovarian toxicity, and a lower, but not significantly, risk of marrow restraint, while there was no obvious association between CYP2C19*2polymorphism and hepatic dysfunction. The CYP2C19*2polymorphism, especially the carrier of A-allele, might reduce the clinical response to cyclophosphamide(CTX) in patients with lupus nephritis.Conclusion:1. FcyRIIIA polymorphisms might be related to SLE in Chinese population. The homozygous FF genotype of FcγRIIIA might be the risk factor for LN, while the homozygous W genotype might be the protective factor for late onset lupus nephritis.2. CD24polymorphisms might be related to SLE in Chinese population, and T allele of CD24might play a role in susceptibility to SLE, while no association is found for neuropsychiatric lupus erythematosus(NPLE).3. The CYP2C19*2polymorphism might influence the clinical response to cyclophosphamide(CTX) in patients with lupus nephritis, and may lower the risk of some toxicity of CTX.