Gershoni-Baruch Ruth, Brik Riva, Lidar Merav, Shinawi Marwan, Livneh Avi
Department of Human Genetics, Rambam Medical Center, Haifa, Israel.
J Rheumatol. 2003 Feb;30(2):308-12.
Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by attacks of fever, serositis, and a predisposition to the development of amyloidosis. The wide clinical variability of the disease has been partly attributed to MEFV allelic heterogeneity and partly to the influence of additional genetic and/or environmental modifiers. Of these, male sex was found to influence disease penetrance and susceptibility to amyloidosis. We investigated the role of sex as an independent contributor to the phenotypic profile in FMF and further defined the factors affecting disease expression and severity.
A total of 124 patients with FMF who were all homozygous for the M694V mutation, including 47 patients with nephropathic amyloidosis, were identified. A detailed chart review and physical examination were undertaken to determine demographic characteristics, history, clinical manifestations, and treatment, and we calculated the disease severity score from the Tel-Hashomer key.
A preponderance of male patients was documented (73:51; 1.4). The overall male:female ratio was significantly higher among patients with amyloidosis (32:15; 2.1) compared to patients without amyloidosis (41:36; 1.1). FMF severity scores, independently calculated for male and female patients, were equally high (9.5 +/- 3.0 and 9.7 +/- 2.8, respectively). The frequency of arthritic attacks, significantly higher in women than men (p = 0.015), remained notably higher in male FMF patients with amyloidosis compared to male FMF patients without amyloidosis (p = 0.002). Significant correlation between arthritis attacks and amyloidosis was found (R > 0.285, p < 0.001).
Susceptibility to renal amyloidosis is influenced both by sex and the occurrence of joint attacks, acting as 2 MEFV independent factors (OR 2.37, 95% CI 1.06-5.26 and OR 3.27, 95% CI 1.23-8.68, respectively).
家族性地中海热（FMF）是一种常染色体隐性疾病，其特征为发热、浆膜炎发作以及易发生淀粉样变性。该疾病广泛的临床变异性部分归因于MEFV等位基因异质性，部分归因于其他遗传和/或环境修饰因素的影响。其中，男性被发现会影响疾病的外显率和对淀粉样变性的易感性。我们研究了性别作为FMF表型特征独立影响因素的作用，并进一步明确了影响疾病表现和严重程度的因素。
共纳入124例均为M694V突变纯合子的FMF患者，其中47例患有肾病性淀粉样变性。进行详细的病历回顾和体格检查以确定人口统计学特征、病史、临床表现和治疗情况，并根据Tel-Hashomer评分标准计算疾病严重程度评分。
记录显示男性患者占多数（73:51；1.4）。与无淀粉样变性的患者（41:36；1.1）相比，淀粉样变性患者中的总体男女比例显著更高（32:15；2.1）。分别独立计算的男性和女性患者的FMF严重程度评分同样高（分别为9.5±3.0和9.7±2.8）。关节炎发作频率在女性中显著高于男性（p = 0.015），在患有淀粉样变性的男性FMF患者中仍显著高于无淀粉样变性的男性FMF患者（p = 0.002）。发现关节炎发作与淀粉样变性之间存在显著相关性（R>0.285，p<0.001）。
对肾淀粉样变性的易感性受性别和关节发作的影响，它们是两个独立的MEFV影响因素（OR分别为2.37，95%CI 1.06 - 5.26和OR 3.
