ABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of FCGR3A gene in susceptibility to systemic lupus erythematosus (SLE) using family based studies.</p><p><b>METHODS</b>A total of 119 patients from 95 nuclear families, with SLE according to the American College of Rheumatology 1997 criteria were recruited. In addition, 316 family members of these patients were also genotyped. A family-based association study was used to explore the association between gene polymorphism and SLE. The authors studied the single nucleotide polymorphisms (SNP) encoding non-synonymous substitution in the cFCGR3A gene with respect to genetic susceptibility to SLE. The FCGR3A gene was genotyped with RFLP.</p><p><b>RESULTS</b>Among 119 SLE patients, the frequency of FCGR3A-72R/S, R and S allele were 39.4% and 60.6%; the frequency of FCGR3A R/S RR, RS and SS genotypes were 9.1%, 60.6% and 30.3%, respectively. Univariate (single marker) family-based association tests (FBATs) demonstrated that variant allele at the SNP(rs403016) in exon 3 of FCGR3A gene was significantly associated with genetic susceptibility to SLE in Additive Model(Z=2.544, P =0.01097) and Recessive Model(Z = 2.198, P = 0.02795). TDT analysis showed an excess of the allele of R from heterozygous parents to affected offspring (chi square was 9.30, P=0.0032).</p><p><b>CONCLUSION</b>The findings suggest that the FCGR3A gene may be the susceptible gene of SLE in Chinese population, and that the individual carrying FCGR3A 72R allele was significantly associated with increase of susceptibility to SLE.</p>
Subject(s)
Adult , Female , Humans , Male , Family , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , Lupus Erythematosus, Systemic , Genetics , Polymorphism, Single Nucleotide , Receptors, IgG , GeneticsABSTRACT
Objective The aim of this study is to investigate the role of angiotensin-converting enzyme (ACE)gene susceptibility to systemic lupus erythematosus(SLE)by familial studies.Methods PCR-based re- striction fragment length polymorphism(RFLP)was applied to genotype single nucleotide polymorphism(SNP) G261T of the ACE gene.A total of 119 patients with SLE from 119 families were recruited.In addition,316 family members of these patients were also genotyped.A family-based association study was carried out to ex- plore the association between gene polymorphism and SLE.We studied the SNP encoding non-synonymous substitution in the ACE gene with respect to genetic susceptibility to SLE.Results Among 119 SLE patients. the frequency of ACEG261TG,T alleles was 44.8%.55.2% respectively,the frequency of ACEG261T GG,GT and TT genotypes was 13.9%,62.0%,24.1% respectively,Univariate(single-marker)family-based association test(FBAT)demonstrated that variant alleles at the SNP,rs4303,exon 5 of ACE gene were significantly asso- ciated with genetic susceptibility to SLE in Additive Model(Z=2.877,P=0.004),Dominant Model(Z=2.557, P=0.011).Recessive Model(Z=2.202,P=0.028).Transmission-disequilibrium test(TDT)and sib transmission -disequilibrium test(STDT)showed an excess of the allele of T from heterozygous parents to affected offspring or higher frequency of the allele of T in the patients than their normal siblings(X~2=11.66,P=0.001).Conclu- sion Our findings suggest that the ACE gene may he the susceptible gene to SLE in Chinese population,and the individuals carrying ACE-261T allele is significantly associated with susceptibility to SLE.