Familial cutaneous collagenomas resulting from a novel mutation in LEMD3

BACKGROUND: The MDM2 oncoprotein promotes cell survival and cell cycle progression by inhibiting the p53 tumour suppressor protein. Further, overexpression of the MDM2 gene can inhibit DNA double-strand break repair in a p53-independent manner. Recent studies have shown that a single nucleotide polymorphism (SNP) in the intronic promoter region of MDM2 (called SNP309) can significantly change the expression of MDM2 and thereby suppress the p53 pathway. This SNP was also found to be associated with the onset and risk of different cancer types. Basal cell carcinoma of the skin (BCC) is one of the most common neoplasms in the world. BCC development is associated with environmental factors (especially sun exposure) as well as heritable factors. OBJECTIVES: The present case-control study investigated the association of the MDM2 SNP309 with the risk and the age at onset of BCC. Methods Data from 509 individuals affected by BCC and 513 healthy controls were genotyped with TaqMan polymerase chain reaction. RESULTS: Cases and controls showed a similar genotype distribution and the SNP did not modify the age at onset of BCC. CONCLUSIONS: These results suggest that the MDM2 SNP309 alone affects neither the risk nor the age at onset of BCC.     

TNFSF4基因多态性与系统性红斑狼疮的相关性研究

目的 探讨湖北汉族人群OX40配体蛋白基因rs844648位点和rs3850641位点基因多态性与SLE的相关性.方法 SLE患者82例和正常人对照组100例,采用PCR及限制性片段长度多态性方法(PCR-RFLP)检测TNFSF4基因rs844648和rs3850641位点多态性分布.结果 ①SLE组rs844648位点AA、AG和GG基因型频率分别为20.7％、62.2％、17.1％,正常人对照组为14.0％、55.0％、31.0％.SLE组rs844648多态性位点A等位基因携带者显著高于正常人对照组[73.2％比69.0％％,x2=4.69,P＜0.05,OR值=2.182( 1.068～ 4.458)],SLE组与正常人对照组间差异有统计学意义;②SNP位点rs3850641的正常人对照组AA、AG和GG基因型频率分别是76.0％、21.0％和3.0％,而SLE组分别为62.2％、31.7％和6.1％,SLE组rs3850641位点G等位基因携带者显著高于正常人对照组[37.8％比24.0％,x2=4.07,P＜0.05,OR值=1.925 (1.015 ～ 3.651)],SLE组与正常人对照组间差异有统计学意义.结论 TNFSF4基因rs844648和rs3850641位点存在单核苷酸多态性变异,该多态性与湖北地区汉族人群SLE的发病有相关性.     

IL-10,IL-6及IL-6受体基因多态性与皮肤黑素瘤易感性的关系

目的 探讨白介素10(IL-10)、白介素6(IL-6)及其受体(IL-6R)基因多态性与黑素瘤易感性的关系.方法 收集30例黑素瘤患者和30例健康时照者的外周血样本进行基因型分析.对于IL-6及IL-6R,选择11种单核苷酸多态性(SNPs),并且每种SNPs分为杂合子组、纯合子变异体组和野生型组进行分析.对于IL-...     

Eotaxin gene single nucleotide polymorphisms in the promoter and exon regions are not associated with susceptibility to atopic dermatitis,but two of them in the promoter region are associated with serum IgE levels in patients with atopic dermatitis

Eotaxin is believed to play an important role in atopic dermatitis (AD) as a potent chemoattractant and activator of eosinophils and Th2 lymphocytes. The eotaxin gene is located at chromosome 17q21.1-q21.2, and linkage findings of AD on chromosome 17 were reported. Recently we have identified single nucleotide polymorphisms (SNPs) of eotaxin gene (-426C > T, -384A > G, 67G > A). To learn whether eotaxin gene SNPs are associated with susceptibility to AD or phenotypes of AD, we investigated the genotype frequencies at each SNP of the gene in AD patients and in controls. We examined 140 Japanese AD patients and 140 healthy Japanese individuals. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. No significant difference was observed in allele or genotype frequencies of any SNP between AD patients and controls. Serum immunoglobulin E (IgE) levels were significantly lower in CT and TT genotype than in CC (P = 0.038) in -426C > T SNP, and lower in GG than in AA and AG with borderline significance (P = 0.053) in -384A > G SNP in AD patients. Eotaxin gene SNPs in the promoter and exon regions are not associated with susceptibility to AD, but two of them in the promoter region are associated with phenotype of AD.     

GABRP基因多态性与系统性红斑狼疮发病易感性的相关性

目的:明确γ氨基丁酸A受体π亚基(GABRP)基因单核苷酸多态性与系统性红斑狼疮(SLE)发病易感性之间的关系。方法:PCR扩增111例SLE患者和120名正常对照者外周血目的基因片段,通过二代测序对目的基因片段进行测序检测rs929763位点和rs3805455位点的多态性。结果:GABRP rs929763TT、AT基因型频率在SLE组与对照组中分别为99.1%、0.9%和95.8%、4.2%,差异无统计学意义(P0.05)。GABRP rs3805455AG、AA、GG基因型频率在SLE组与对照组中分别为45.0%、9.9%、45.0%和45.8%、8.3%、45.0%,差异无统计学意义(P0.05),A、G等位基因频率在SLE组与对照组中分别为32.4%、67.5%和50.0%、50.0%,差异无统计学意义(P0.05)。结论:GABRP基因SNP位点rs929763和rs3805455多态性可能与SLE的发病无关。     

Promoter polymorphisms of the HLA-G gene, but not the HLA-E and HLA-F genes, is associated with non-segmental vitiligo patients in the Korean population

The aim of this study was to determine whether or not promoter polymorphisms of the class I major histocompatibility complex (HLA-E, HLA-F, and HLA-G) are associated with susceptibility to vitiligo. To identify a possible association with vitiligo, 241 patients with non-segmental vitiligo (NSV) and 395 healthy controls were recruited in this study. Three promoter single nucleotide polymorphisms (SNPs; rs1264459 of HLA-E, rs9258170 of HLA-F, and rs1736936 of HLA-G) were analyzed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and direct sequencing. Multiple logistic regression models (co-dominant 1, co-dominant 2, dominant, recessive, and log-additive models) were applied for odds ratios (ORs), 95% confidence intervals (CIs), and P values. To obtain the defined results, P values were recalculated by a Bonferroni correction. After the Bonferroni correction, the genotype of the SNP (rs1736936) of HLA-G was shown to have significant association with NSV (P = 0.045 in the recessive model). The genotype frequencies of the HLA-G SNP (rs1736936) had a significant correlation with the age of onset of NSV (P = 0.016 in the co-dominant 1 model and P = 0.027 in the dominant model). Our results suggest that HLA-G, but not HLA-E and HLA-F, may be associated with susceptibility to NSV in the Korean population.     

PTPN22 is genetically associated with risk of generalized vitiligo, but CTLA4 is not

Generalized vitiligo is an acquired, multifactorial, polygenic disease in which depigmented spots of skin, overlying hair, and mucus membranes result from autoimmune-mediated loss of melanocytes from affected areas. We examined single-nucleotide polymorphisms (SNPs) in the PTPN22 and CTLA4 genes in 126 Caucasian families with multiple cases of generalized vitiligo and associated autoimmune diseases, using a family-based association study design. The PTPN22 1858T allele of SNP rs2476601 is significantly associated both with generalized vitiligo and with an expanded autoimmunity phenotype. Individuals carrying the PTPN22 1858T allele had an allelic odds ratio (OR) of 2.16 for generalized vitiligo and a genotypic OR of 2.35 as C/T heterozygotes. Similarly, individuals carrying the PTPN22 1858T allele had an allelic OR of 2.05 for the expanded autoimmunity phenotype, and a genotypic OR of 2.19 for C/T heterozygotes. Examination of five SNPs in the CTLA4 gene (rs1863800, rs231775, rs3087243, rs11571302, rs11571297, rs10932037) in the same 126 families yielded no evidence of allelic or genotypic association with either generalized vitiligo or the expanded autoimmune phenotype. These results implicate PTPN22 in mediating susceptibility to generalized vitiligo and associated autoimmune diseases, but do not support a role for CTLA4.     

广西壮族、汉族系统性红斑狼疮与Toll样受体9基因多态性研究

目的 探讨TLR9单核苷酸多态性与广西系统性红斑狼疮（SLE）患者发病的相关性,以及其在壮族、汉两个民族间的差异。 方法 聚合酶链反应-限制性酶切技术、聚合酶链反应-限制性片段长度多态性分析技术（PCR-RFLP）对97例广西SLE患者和202例广西健康对照者的TLR9基因多态性进行检测,分析其基因型和等位基因频率与SLE部分临床实验室指标的关联性,并比较两民族间的差异。 结果 TLR9 rs352140CC、CT、TT基因型频率在汉族SLE组与汉族对照组中分别为42.9%、41.1%、16.1%和38.3%、55.8%、5.8%,差异有统计学意义（P < 0.05）,其C、T等位基因频率差异无统计学意义（P > 0.05）。TLR9rs352140 C/T基因型频率和等位基因频率在壮族SLE组与壮族健康对照组间、壮族SLE组与汉族SLE组间差异无统计学意义（均P > 0.05）。TLR9 rs352140TT基因型频率在ds-DNA阳性组比阴性组高（P < 0.05）,而T等位基因频率在两组间差异无统计学意义（P > 0.05）。TLR9 rs352140TT基因型频率和T等位基因的频率在SLEDAI ≥ 9组比SLEDAI < 9组高,差异有统计学意义（均P < 0.05）。TLR9 rs352140TT基因型频率和T等位基因的频率在ANA阳性组与阴性组间差异无统计学意义（均P > 0.05）。 结论 TLR9 rs352140基因多态性可能与广西汉族人SLE的易感性有关, TLR9基因多态性与部分SLE指标可能具有相关性。     

Lack of association between the promoter polymorphisms at positions -308 and -238 of the tumor necrosis factor alpha gene and psoriasis vulgaris in Japanese patients

BACKGROUND: Psoriasis features an increased level and activity of tumor necrosis factor alpha (TNF-alpha). The TNF-alpha gene has single nucleotide polymorphisms (SNPs) at positions -308 (-308G>A) and -238 (-238G>A) in the promoter region, and the -238G>A SNP has been reported to be associated with psoriasis vulgaris (PV) and psoriatic arthritis in Caucasians. OBJECTIVE: To examine whether these SNPs are associated with susceptibility to PV in Japanese patients, we investigated the genotype and allele frequencies at each SNP in Japanese PV patients and in controls. METHODS: We examined 163 PV patients and 96 healthy individuals. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: No significant association between the genotypes or alleles of these SNPs and susceptibility to PV was observed. CONCLUSION: These SNPs themselves are not associated with susceptibility to PV in the Japanese.     

IL2RA-RBM17基因区域单核苷酸多态性与中国蒙古族白癜风关联研究

目的 探讨IL2RA-RBM17基因区域单核苷酸多态性与中国蒙古族白癜风的遗传关联性.方法 收集白癜风患者425例,健康对照503例.用AxyPrep(AP-MX-BL-GDNA-25)基因组DNA抽提试剂盒抽提基因组DNA.选择位于IL2RA-RBM17基因区域的9个单核苷酸多态性(rs706779、rs3134883、rs7090530、rs12251307、rs4750005、rs3920615、rs4747887、rs4750012、rs7099083),用连接酶链反应进行基因分型.用PLINK1.07及SPSS11.0进行统计分析,x2检验比较白癜风组及健康对照组等位基因频率及基因型频率.对5个差异有统计学意义的SNP间进行连锁不平衡检验,计算两两间的r2和D'值.用5个具有相关性的SNP构建单倍型,分析每个单倍型频率在白癜风组和健康对照组中的分布.结果 5个SNP (rs4750005、rs3920615、rs4747887、rs4750012、rs7099083)的等位基因频率与健康对照组差异有统计学意义(P＜0.05).5个SNP在显性遗传模式下,白癜风组中的基因型频率均显著低于健康对照组(P＜ 0.005 6).5个差异有统计学意义的SNP间存在中等至强的连锁不平衡(D'=0.424 ～1,r2=0.137 ～ 0.985).用5个具有相关性的SNP构建单倍型,分析每个单倍型频率的分布,发现1个单倍型(H2:CGCTA)在白癜风组频率明显低于健康对照组,并达到Bonferroni校正水平(P=0.001 6,OR=0.674).结论 IL2RA-RBM17区域基因多态性与蒙古族白癜风具有相关性.     

Investigation of the eotaxin gene -426C-->T, -384A-->G and 67G-->a single-nucleotide polymorphisms and atopic dermatitis in Italian children using family-based association methods.

BACKGROUND: Eotaxin plays an important role in atopic dermatitis (AD) as a potent chemoattractant and activator of eosinophils and T-helper 2 lymphocytes. AIM: To investigate whether single-nucleotide polymorphisms of the eotaxin gene are associated with AD, we investigated the genotype and allelic frequencies of -426C-->T, -384A-->G, and 67G-->A SNPs in 130 Italian families. METHODS: In total, 130 children with either the extrinsic allergic or intrinsic nonallergic forms of AD (EAD and IAD) were recruited from 130 families. Genotyping was performed using PCR and restriction fragment length polymorphism analysis. RESULTS: A significant difference was observed in the genotype frequency of the -426C-->T SNP between children with EAD and those with IAD (P = 0.01), and between children with EAD and controls (P = 0.01). The allele frequencies of the -426C-->T SNP were significantly different between children with EAD and those with IAD (P < 0.01), and between children with EAD and controls (P < 0.01). For children with EAD, the genotype frequency of the -426C-->T SNP was no different between the groups with mild, moderate and severe SCORAD (P = NS). No significant association was observed between the -384A-->G and 67G-->A SNPs and the two groups of children with EAD and IAD compared with the control group. In 32 trios selected from 68 EAD families, the transmission disequilibrium test showed a preferential transmission of the -426T allele from the parents to affected offspring (P < 0.01). CONCLUSIONS: Our results suggest that in our group of children with AD, the eotaxin gene may play a crucial role in the development of extrinsic AD, probably with other genetic factors.     

Polymorphisms within the C3 gene are associated with specific IgE levels to common allergens and super-antigens among atopic dermatitis patients

Abstract:  Atopic dermatitis (AD) is a chronic inflammatory skin disease. Twin and family studies suggest a strong genetic component of the disease. The keratinocytes secrete high amounts of C3 after stimulation with pro-inflammatory cytokines, which may play a functional role in skin inflammation. In this study, we genotyped four different single nucleotide polymorphisms (SNPs) by melting curve analysis using sequence specific hybridization probes in a well-characterized cohort of AD patients. Among four SNPs within C3 gene, higher frequencies of rs10410674 (23.5% vs 12.2%) and rs366510 (13.8% vs 6.5%) were observed in AD patients as compared with control group. None of the tested polymorphisms showed significant association with the risk of the disease phenotype. Analysis of rs10402876 SNP revealed its association with less severe AD disease expression (low SCORAD). Total serum IgE levels were not different among AD patients having any of the four SNPs. However, we observed significantly less serum-specific IgE levels to common allergens ( Dermatophagoides pteronyssinus and birch pollens) and Staphylococcal enterotoxin B in AD patients having rs366510 SNP. Thus, associations of polymorphism within C3 gene with less severe AD disease expression and a weaker sensitization to common allergens suggest the role of these SNPs in the development of AD.     

Toll样受体9基因多态性与尖锐湿疣的研究

目的探讨Toll样受体9的单核苷酸多态性与尖锐湿疣(CA)发病的相关性.方法抽取63例CA患者和23例正常人对照组的外周静脉血,采用TLR9基因直接测序的方法分析TLR9受体的单核苷酸多态性.结果 TLR9基因自翻译起始点第1 174、1635、1269、1724位均存在单核苷酸多态性位点,分别称为SNP1、SNP2、SNP3和SNP4,其中SNP3、SNP4为新发现位点,SNP1、SNP2为NCBI数据库中公布的位点,登录号分别为rs352139、rs352140.CA患者与正常人对照组的SNP1位点的等位基因A的频率分别为0.690、0.609,等位基因G的频率0.309、0.391,两组间比较差异均无统计学意义(P>0.05).SNP2位点的等位基因A的频率分别为0.302、0.369,等位基因G的频率0.698、0.630,两组间比较差异无统计学意义(P>0.05).SNP1、SNP2两个多态性位点存在4种单倍体型,分别为AA、AG、GA、GG.每种单倍体型在CA患者组和正常人对照组间比较差异均无统计学意义(P>0.05).结论 TLR9基因在广东汉族人群中存在4个单核苷酸多态性位点,分别为SNP1、SNP2、SNP3、SNP4.SNP1、SNP2两位点与CA的发病易感性可能无相关性.     

Toll样受体9基因多态性与尖锐湿疣的研究

目的探讨Toll样受体9的单核苷酸多态性与尖锐湿疣(CA)发病的相关性.方法抽取63例CA患者和23例正常人对照组的外周静脉血,采用TLR9基因直接测序的方法分析TLR9受体的单核苷酸多态性.结果 TLR9基因自翻译起始点第1 174、1635、1269、1724位均存在单核苷酸多态性位点,分别称为SNP1、SNP2、SNP3和SNP4,其中SNP3、SNP4为新发现位点,SNP1、SNP2为NCBI数据库中公布的位点,登录号分别为rs352139、rs352140.CA患者与正常人对照组的SNP1位点的等位基因A的频率分别为0.690、0.609,等位基因G的频率0.309、0.391,两组间比较差异均无统计学意义(P>0.05).SNP2位点的等位基因A的频率分别为0.302、0.369,等位基因G的频率0.698、0.630,两组间比较差异无统计学意义(P>0.05).SNP1、SNP2两个多态性位点存在4种单倍体型,分别为AA、AG、GA、GG.每种单倍体型在CA患者组和正常人对照组间比较差异均无统计学意义(P>0.05).结论 TLR9基因在广东汉族人群中存在4个单核苷酸多态性位点,分别为SNP1、SNP2、SNP3、SNP4.SNP1、SNP2两位点与CA的发病易感性可能无相关性.     

Toll样受体9基因多态性与尖锐湿疣的研究

目的 探讨Toll样受体9的单核苷酸多态性与尖锐湿疣（CA）发病的相关性。方法 抽取63例CA患者和23例正常人对照组的外周静脉血,采用TLR9基因直接测序的方法分析TLR9受体的单核苷酸多态性。结果 TLR9基因自翻译起始点第1174、1635、1269、1724位均存在单核苷酸多态性位点,分别称为SNP1、SNP2、SNP3和SNP4,其中SNP3、SNP4为新发现位点,SNP1、SNP2为NCBI数据库中公布的位点,登录号分别为rs352139、rs352140。CA患者与正常人对照组的SNP1位点的等位基因A的频率分别为0.690、0.609,等位基因G的频率0.309、0.391,两组间比较差异均无统计学意义（P ＞ 0.05）。SNP2位点的等位基因A的频率分别为0.302、0.369,等位基因G的频率0.698、0.630,两组间比较差异无统计学意义（P ＞ 0.05）。SNP1、SNP2两个多态性位点存在4种单倍体型,分别为AA、AG、GA、GG。每种单倍体型在CA患者组和正常人对照组间比较差异均无统计学意义（P ＞ 0.05）。结论 TLR9基因在广东汉族人群中存在4个单核苷酸多态性位点,分别为SNP1、SNP2、SNP3、SNP4。SNP1、SNP2两位点与CA的发病易感性可能无相关性。     

Toll样受体9基因多态性与尖锐湿疣的研究

目的探讨Toll样受体9的单核苷酸多态性与尖锐湿疣(CA)发病的相关性.方法抽取63例CA患者和23例正常人对照组的外周静脉血,采用TLR9基因直接测序的方法分析TLR9受体的单核苷酸多态性.结果 TLR9基因自翻译起始点第1 174、1635、1269、1724位均存在单核苷酸多态性位点,分别称为SNP1、SNP2、SNP3和SNP4,其中SNP3、SNP4为新发现位点,SNP1、SNP2为NCBI数据库中公布的位点,登录号分别为rs352139、rs352140.CA患者与正常人对照组的SNP1位点的等位基因A的频率分别为0.690、0.609,等位基因G的频率0.309、0.391,两组间比较差异均无统计学意义(P>0.05).SNP2位点的等位基因A的频率分别为0.302、0.369,等位基因G的频率0.698、0.630,两组间比较差异无统计学意义(P>0.05).SNP1、SNP2两个多态性位点存在4种单倍体型,分别为AA、AG、GA、GG.每种单倍体型在CA患者组和正常人对照组间比较差异均无统计学意义(P>0.05).结论 TLR9基因在广东汉族人群中存在4个单核苷酸多态性位点,分别为SNP1、SNP2、SNP3、SNP4.SNP1、SNP2两位点与CA的发病易感性可能无相关性.     

8-羟鸟嘌呤DNA转葡糖基酶1基因多态性位点rs1052133与汉族人群白癜风的相关性研究

目的 探讨中国汉族人群8-羟鸟嘌呤DNA转葡糖基酶1（OGG1）基因功能性单核苷酸多态性（SNP） rs1052133（C/G）位点与白癜风的相关性。方法 白癜风患者800例和健康对照组800例,采用PCR及限制性片段长度多态性方法（PCR-RFLP）检测OGG1基因rs1052133位点多态性分布,χ2检验和非条件Logistic回归分析评估该位点多态性与白癜风罹患危险的相关性。白癜风患者83例和健康对照组83例,采用8-羟基脱氧鸟苷（8-OHdG） ELISA检测试剂盒检测外周血血清中8-OHdG的水平,采用t检验分析两组之间的差异。结果 白癜风组rs1052133位点CC、CG和GG基因型频率分别为16.8%、54.0%、29.2%,健康对照组为21.4%、52.8%、25.8%,两组间差异有统计学意义（χ2 = 6.26,P < 0.05）。白癜风组rs1052133位点G等位基因携带者显著高于健康对照组（56.2%比52.2%,χ2 = 5.16,P < 0.05）。携带有rs1052133位点CG或GG基因型的个体罹患白癜风的危险性显著增加［CG基因型χ2 = 3.98,P < 0.05,校正OR值 = 1.31 （1.01 ～ 1.70）;CG基因型χ2 = 6.01,P < 0.05,校正OR值 = 1.45 （1.08 ～ 1.94）］,尤其是女性患者、非节段型、病情活动、病程较长、有家族史、无伴发自身免疫性疾病的患者。携带有rs1052133位点CG或GG基因型的白癜风患者外周血血清中8-OHdG的水平显著高于携带CC基因型的患者,8-OHdG水平分别为（838.23 ± 294.11） ?滋g/L和（593.84 ± 190.14） ?滋g/L,两组比较,t = 3.63,P < 0.01。结论 OGG1基因功能性SNP rs1052133位点的多态性与白癜风的发病紧密相关,可能由其修复能力降低所致。 【关键词】 白癜风; 多态性,单核苷酸; OGG1基因; 8-羟基脱氧鸟苷     

Genome-wide meta-analysis of psoriatic arthritis identifies susceptibility locus at REL

Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease affecting up to 30% of psoriasis vulgaris (PsV) cases and approximately 0.25 to 1% of the general population. To identify common susceptibility loci, we performed a meta-analysis of three imputed genome-wide association studies (GWAS) on psoriasis, stratified for PsA. A total of 1,160,703 single-nucleotide polymorphisms (SNPs) were analyzed in the discovery set consisting of 535 PsA cases and 3,432 controls from Germany, the United States, and Canada. We followed up two SNPs in 1,931 PsA cases and 6,785 controls comprising six independent replication panels from Germany, Estonia, the United States, and Canada. In the combined analysis, a genome-wide significant association was detected at 2p16 near the REL locus encoding c-Rel (rs13017599, P=1.18 × 10(-8), odds ratio (OR)=1.27, 95% confidence interval (CI)=1.18-1.35). The rs13017599 polymorphism is known to associate with rheumatoid arthritis (RA), and another SNP near REL (rs702873) was recently implicated in PsV susceptibility. However, conditional analysis indicated that rs13017599, rather than rs702873, accounts for the PsA association at REL. We hypothesize that c-Rel, as a member of the Rel/NF-κB family, is associated with PsA in the context of disease pathways that involve other identified PsA and PsV susceptibility genes including TNIP1, TNFAIP3, and NFκBIA.     

A novel single-nucleotide polymorphism of the Fcgamma receptor IIIa gene is associated with genetic susceptibility to systemic lupus erythematosus in Chinese populations: a family-based association study

BACKGROUND: Systemic lupus erytematosus (SLE) is characterized by the presence of various autoantibodies and the deposition of immune complexes which are cleared by Fcgamma receptors. OBJECTIVES: Family-based association analysis was performed to investigate whether the FCGR3A-72S/R and FCGR3A-270T/R polymorphisms are risk factors for SLE in a Chinese population. METHODS: In total, 119 patients with SLE from 95 nuclear families, aged 14-78 years, who met the American College of Rheumatology 1997 criteria were recruited, as were 316 family members of these patients. We studied two single-nucleotide polymorphisms (SNPs) encoding nonsynonymous substitution in the FCGR3A gene with respect to genetic susceptibility to SLE in a collection of 435 subjects from 95 nuclear families. We performed the genotyping using PCR restriction fragment length polymorphism. RESULTS: Our results showed that FCGR3A-72R/S have an excess of transmission of the R allele from heterozygous parents to affected offspring (transmission disequilibrium test chi2 = 9.30, P = 0.0032). Univariate (single-marker) family-based association tests demonstrated that a variant allele at SNP rs403016 of the FCGR3A gene was significantly associated with genetic susceptibility to SLE (exon 3, Z = 2.5444, P = 0.01097) in an additive model. The R and S allele frequencies were 39.4% and 60.6%, respectively. The frequencies of FCGR3A 72R/R, R/S and SS genotypes were 9.1%, 60.6% and 30.3%, respectively. However, the FCGR3A-270T/S SNP was not found in this Chinese population. CONCLUSION: This study suggests a linkage disequilibrium of the FCGR3A-72R/S SNP with SLE, and supports the notion that a novel polymorphism of the FCGR3A-72R/S SNP is associated with genetic susceptibility to SLE in Chinese populations.