Canosa Antonio, Calvo Andrea, Mora Gabriele, Moglia Cristina, Brunetti Maura, Barberis Marco, Borghero Giuseppe, Caponnetto Claudia, Trojsi Francesca, Spataro Rossella, Volanti Paolo, Simone Isabella Laura, Salvi Fabrizio, Logullo Francesco Ottavio, Riva Nilo, Tremolizzo Lucio, Giannini Fabio, Mandrioli Jessica, Tanel Raffaella, Murru Maria Rita, Mandich Paola, Conforti Francesca Luisa, Zollino Marcella, Sabatelli Mario, Tarlarini Claudia, Lunetta Christian, Mazzini Letizia, D'Alfonso Sandra, Guy Nathalie, Meininger Vincent, Clavelou Pierre, Camu William, Chiò Adriano
ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, 10126 Turin, Italy.
SC Neurologia 1U, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, 10126 Turin, Italy.
Biomedicines. 2023 Feb 24;11(3):704. doi: 10.3390/biomedicines11030704.
: Data from published studies about the effect of HFE polymorphisms on ALS risk, phenotype, and survival are still inconclusive. We aimed at evaluating whether the p.H63D polymorphism is a modifier of phenotype and survival in -mutated patients. : We included 183 -mutated ALS patients. Mutations were classified as severe or mild according to the median survival of the study population. Patients were screened for the p.H63D polymorphism. Survival was calculated using the Kaplan-Meier modeling, and differences were measured by the log-rank test. Multivariable analysis was performed with the Cox proportional hazards model (stepwise backward). : severe mutation carriers show more frequent familial history for ALS and shorter survival compared to mild mutation carriers. Carriers and non-carriers of the p.H63D polymorphism did not differ in terms of sex ratio, frequency of positive familial history, age at onset, and bulbar/spinal ratio. In univariate and in Cox multivariable analysis using sex, age at onset, site of onset, family history, country of origin, and mutation severity as covariates, p.H63D carriers had a longer survival ( = 0.034 and = 0.004). : We found that -mutated ALS patients carrying the p.H63D HFE polymorphism have a longer survival compared to non-carriers, independently of sex, age and site of onset, family history, nation of origin, and severity of mutations, suggesting a possible role as disease progression modifier for the p.H63D polymorphism in -ALS.
关于HFE基因多态性对肌萎缩侧索硬化症（ALS）风险、表型和生存影响的已发表研究数据尚无定论。我们旨在评估p.H63D基因多态性是否是突变患者表型和生存的修饰因子。
我们纳入了183例突变的ALS患者。根据研究人群的中位生存期将突变分为严重或轻度。对患者进行p.H63D基因多态性筛查。使用Kaplan-Meier模型计算生存率，并通过对数秩检验测量差异。采用Cox比例风险模型（逐步向后法）进行多变量分析。
与轻度突变携带者相比，严重突变携带者显示出更频繁的ALS家族史且生存期更短。p.H63D基因多态性的携带者和非携带者在性别比例、阳性家族史频率、发病年龄和延髓/脊髓比例方面没有差异。在使用性别、发病年龄、发病部位、家族史、原籍国和突变严重程度作为协变量的单变量和Cox多变量分析中，p.H63D基因多态性的携带者生存期更长（P = 0.034和P = 0.004）。
我们发现，与非携带者相比，携带p.H63D HFE基因多态性的突变ALS患者生存期更长，且与性别、年龄、发病部位、家族史、原籍国和突变严重程度无关，这表明p.H63D基因多态性在ALS中可能作为疾病进展修饰因子发挥作用。
