意大利大陆地区居民和撒丁岛居民中多发性硬化症变异的负担。

The burden of multiple sclerosis variants in continental Italians and Sardinians.

作者信息

Barizzone Nadia, Zara Ilenia, Sorosina Melissa, Lupoli Sara, Porcu Eleonora, Pitzalis Maristella, Zoledziewska Magdalena, Esposito Federica, Leone Maurizio, Mulas Antonella, Cocco Eleonora, Ferrigno Paola, Guerini Franca R, Brambilla Paola, Farina Gabriele, Murru Raffaele, Deidda Francesca, Sanna Sonia, Loi Alessia, Barlassina Cristina, Vecchio Domizia, Zauli Andrea, Clarelli Ferdinando, Braga Daniele, Poddie Fausto, Cantello Roberto, Martinelli Vittorio, Comi Giancarlo, Frau Jessica, Lorefice Lorena, Pugliatti Maura, Rosati Giulio, Melis Maurizio, Marrosu Maria G, Cusi Daniele, Cucca Francesco, Martinelli Boneschi Filippo, Sanna Serena, D'Alfonso Sandra

机构信息

Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Novara, Italy/Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.

Centro di Ricerca, Sviluppo e Studi Superiori in Sardegna, Pula Cagliari, Italy/Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Cittadella Universitaria di Monserrato, Cagliari, Italy.

出版信息

Mult Scler. 2015 Oct;21(11):1385-95. doi: 10.1177/1352458515596599.

DOI:10.1177/1352458515596599

PMID:26438306

Abstract

BACKGROUND

Recent studies identified > 100 non-HLA (human leukocyte antigen) multiple sclerosis (MS) susceptibility variants in Northern European populations, but their role in Southern Europeans is largely unexplored.

OBJECTIVE

We aimed to investigate the cumulative impact of those variants in two Mediterranean populations: Continental Italians and Sardinians.

METHODS

We calculated four weighted Genetic Risk Scores (wGRS), using up to 102 non-HLA MS risk variants and 5 HLA MS susceptibility markers in 1691 patients and 2194 controls from continental Italy; and 2861 patients and 3034 controls from Sardinia. We then assessed the differences between populations using Nagelkerke's R(2) and the area under the Receiver Operating Characteristic (ROC) curves.

RESULTS

As expected, the genetic burden (mean wGRS value) was significantly higher in MS patients than in controls, in both populations. Of note, the burden was significantly higher in Sardinians. Conversely, the proportion of variability explained and the predictive power were significantly higher in continental Italians. Notably, within the Sardinian patients, we also observed a significantly higher burden of non-HLA variants in individuals who do not carry HLA risk alleles.

CONCLUSIONS

The observed differences in MS genetic burden between the two Mediterranean populations highlight the need for more genetic studies in South Europeans, to further expand the knowledge of MS genetics.

摘要

背景

近期研究在北欧人群中鉴定出100多个非人类白细胞抗原（HLA）的多发性硬化症（MS）易感性变异，但它们在南欧人群中的作用在很大程度上尚未得到探索。

目的

我们旨在研究这些变异在两个地中海人群（意大利大陆人群和撒丁岛人群）中的累积影响。

方法

我们使用多达102个非HLA MS风险变异和5个HLA MS易感性标记，计算了来自意大利大陆的1691例患者和2194例对照，以及来自撒丁岛的2861例患者和3034例对照的四个加权遗传风险评分（wGRS）。然后，我们使用Nagelkerke's R²和受试者工作特征（ROC）曲线下的面积评估人群之间的差异。