Seligman V A, Suarez C, Lum R, Inda S E, Lin D, Li H, Olson J L, Seldin M F, Criswell L A
Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, USA.
Arthritis Rheum. 2001 Mar;44(3):618-25. doi: 10.1002/1529-0131(200103)44:3<618::AID-ANR110>3.0.CO;2-R.
To determine whether inheritance of Fcgamma receptor (FcgammaR) alleles conferring lower affinity for IgG binding increases the risk of developing lupus nephritis.
We compared the frequency of low-affinity alleles of two FcgammaR polymorphisms (FcgammaRIIA and FcgammaRIIIA) among 235 patients with systemic lupus erythematosus (SLE) and proven nephritis (nephritis patients) and among 352 SLE patients with no evidence of renal disease (non-nephritis control subjects). The ethnic distribution of patients in the study was 49% Caucasian, 20% Hispanic, 17% Asian/Pacific Islander, 12% African American, and 2% from other ethnic groups. All patients were genotyped for the FcgammaRIIA-131R/H and FcgammaRIIIA-158V/F polymorphisms. We used contingency table analysis to compare allele and genotype distributions for nephritis patients and nonnephritis control subjects, including ethnic-specific strata. Multivariate logistic regression analyses included sex and disease duration as covariates.
Univariate and multivariate analyses demonstrated a striking association between the low-affinity FcgammaRIIIA-158F allele and FF genotype and the risk of nephritis among Caucasians, but not among non-Caucasians (multivariate odds ratio [OR] 2.6 for Caucasians with FF genotype), (P = 0.0017). This association was even stronger among Caucasians with severe nephritis (OR 4.4, P < 0.0001). In contrast, inheritance of the low-affinity FcgammaRIIA-131R allele (and RR genotype) was not associated with an increased risk of lupus nephritis among any of the ethnic groups examined.
The FcgammaRIIIA-158F allele is a major risk factor for the development of lupus nephritis among Caucasians, but not among non-Caucasians. These results suggest that ethnic variation is critical in defining the specific genetic factors underlying the pathogenesis of SLE, and they have important prognostic and therapeutic implications as well.
确定对IgG结合亲和力较低的Fcγ受体（FcγR）等位基因的遗传是否会增加患狼疮性肾炎的风险。
我们比较了235例系统性红斑狼疮（SLE）且确诊为肾炎的患者（肾炎患者）和352例无肾脏疾病证据的SLE患者（非肾炎对照受试者）中两种FcγR多态性（FcγRIIA和FcγRIIIA）的低亲和力等位基因频率。研究中患者的种族分布为49%为白种人，20%为西班牙裔，17%为亚裔/太平洋岛民，12%为非裔美国人，2%来自其他种族。所有患者均对FcγRIIA - 131R/H和FcγRIIIA - 158V/F多态性进行基因分型检测。我们使用列联表分析来比较肾炎患者和非肾炎对照受试者的等位基因和基因型分布，包括按种族分层分析。多因素逻辑回归分析将性别和疾病持续时间作为协变量。
单因素和多因素分析表明，低亲和力的FcγRIIIA - 158F等位基因和FF基因型与白种人患肾炎的风险之间存在显著关联，但在非白种人中不存在这种关联（FF基因型白种人的多因素比值比[OR]为2.6），（P = 0.0017）。在患有严重肾炎的白种人中，这种关联更强（OR 4.4，P < 0.0001）。相比之下，在任何所研究的种族群体中，低亲和力的FcγRIIA - 131R等位基因（和RR基因型）的遗传与狼疮性肾炎风险增加无关。
FcγRIIIA - 158F等位基因是白种人患狼疮性肾炎的主要危险因素，但在非白种人中并非如此。这些结果表明，种族差异对于确定SLE发病机制的特定遗传因素至关重要，并且它们也具有重要的预后和治疗意义。
