Vidal-Taboada Jose Manuel, Lopez-Lopez Alan, Salvado Maria, Lorenzo Laura, Garcia Cecilia, Mahy Nicole, Rodríguez Manuel J, Gamez Josep
Biochemistry and Molecular Biology Unit, Department of Physiological Sciences I, Faculty of Medicine, IDIBAPS, Universitat de Barcelona, Casanova 143, 08036, Barcelona, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), Barcelona, Spain.
J Neurol. 2015 Oct;262(10):2285-92. doi: 10.1007/s00415-015-7843-z. Epub 2015 Jul 11.
To investigate the association of functional variants of the human UNC13A gene with the risk of ALS, survival and the disease progression rate in a Spanish ALS cohort. 136 sporadic ALS (sALS) patients and 487 healthy controls were genotyped for the UNC13A rs12608932 variant. Clinical characterization of ALS patients included gender, age at first symptom, initial topography, disease progression rate, and survival. Genetic association was analyzed under five inheritance models. The sALS patients with the rs12608932(CC) genotype had an increased risk of ALS under a recessive genetic model [OR 2.16; 95 % CI (1.23, 3.8), p = 0.009; corrected p = 0.028]. Genotypes with a C allele are also associated with increased risk [OR 1.47; 95 % CI (1.11, 1.95); p = 0.008; corrected p = 0.023] under an additive model. sALS patients with a C/C genotype had a shorter survival than patients with A/A and A/C genotypes [HR 1.44; 95 % CI (1.11, 1.873); p = 0.007] under a recessive model. In an overdominant model, heterozygous patients had a longer survival than homozygous patients [HR 0.36; 95 % CI (0.22, 0.59); p = 0.001]. The rs12608932 genotypes modify the progression of symptoms measured using the ALSFRS-R. No association with age of onset, initial topography or rate of decline in FVC was found. Our results show that rs12608932 is a risk factor for ALS in the Spanish population and replicate the findings described in other populations. The rs12608932 is a modifying factor for survival and disease progression rate in our series. Our results also corroborated that it did not influence the age of onset.
为研究人类UNC13A基因功能变异与西班牙肌萎缩侧索硬化(ALS)队列中ALS风险、生存率及疾病进展率之间的关联。对136例散发性ALS(sALS)患者和487例健康对照进行UNC13A rs12608932变异的基因分型。ALS患者的临床特征包括性别、首发症状年龄、初始发病部位、疾病进展率和生存率。在五种遗传模型下分析基因关联。rs12608932(CC)基因型的sALS患者在隐性遗传模型下患ALS的风险增加[比值比(OR)2.16;95%置信区间(CI)(1.23,3.8),p = 0.009;校正p = 0.028]。在加性模型下,携带C等位基因的基因型也与风险增加相关[OR 1.47;95% CI(1.11,1.95);p = 0.008;校正p = 0.023]。在隐性模型下,C/C基因型的sALS患者比A/A和A/C基因型的患者生存期短[风险比(HR)1.44;95% CI(1.11,1.873);p = 0.007]。在共显性模型下,杂合子患者比纯合子患者生存期长[HR 0.36;95% CI(0.22,0.59);p = 0.001]。rs12608932基因型改变了使用ALS功能评定量表修订版(ALSFRS-R)测量症状的进展情况。未发现与发病年龄、初始发病部位或用力肺活量下降率有关联。我们的结果表明,rs12608932是西班牙人群中ALS的一个风险因素,并重复了其他人群中描述的研究结果。在我们的队列中,rs12608932是生存期和疾病进展率的一个修饰因素。我们的结果还证实它不影响发病年龄。