Montomoli Cristina, Prokopenko Inga, Caria Antonella, Ferrai Raffaela, Mander Adrian, Seaman Shaun, Musu Luigina, Piras Maria L, Ticca Anna F, Murgia Salvatore B, Bernardinelli Luisa
Dipartimento Scienze Sanitarie Applicate e Psicocomportamentali, Sezione di Statistica Medica ed Epidemiologia, Università di Pavia, Italy.
Genet Epidemiol. 2002 Mar;22(3):265-71. doi: 10.1002/gepi.0173.
Studies of twins, adoptees, half siblings, and familial recurrence risk have shown that genetic and non-genetic factors are involved in multiple sclerosis (MS) etiology. Age at onset, gender, and parental MS status seem to influence sibling risk. We studied the recurrence risk in siblings of MS patients in an isolated population of Sardinia, Italy, which is genetically homogeneous, inbred, and very stable, with a high MS frequency. The Aalen-Nelson estimate of the recurrence risk in siblings is 4.7%, and the risk ratio compared with the general population is 31. Proportional hazards models were used to investigate the effect of sibling sex, sex, and age at onset of the proband, and number of affected relatives on a sibling's predicted MS risk. Sib's risk is influenced by age at onset (P = 0.02), and possibly by sex of the proband (P = 0.08). There is also a borderline significant interaction (P = 0.05) between the sex and age at onset of the proband: early age at onset influences sib's risk only if the proband is female. The number of affected relatives in the family is not found to influence sibling risk, but the power is lacking (95% CI 0.50-2.62). This result is consistent with a single dominant gene with an extremely low penetrance, a model that has not yet been disproved as a possible inheritance model for MS.
对双胞胎、领养者、同父异母或同母异父的兄弟姐妹以及家族复发风险的研究表明，遗传因素和非遗传因素均与多发性硬化症（MS）的病因有关。发病年龄、性别以及父母的MS患病状况似乎会影响其兄弟姐妹的患病风险。我们在意大利撒丁岛的一个与世隔绝的人群中研究了MS患者兄弟姐妹的复发风险，该人群基因同质、近亲通婚且非常稳定，MS发病率很高。采用阿伦-尼尔森法估计，兄弟姐妹的复发风险为4.7%，与普通人群相比，风险比为31。使用比例风险模型来研究先证者的兄弟姐妹性别、性别、发病年龄以及受影响亲属的数量对其预测的MS风险的影响。兄弟姐妹的风险受发病年龄影响（P = 0.02），可能也受先证者性别的影响（P = 0.08）。先证者的性别和发病年龄之间还存在临界显著的相互作用（P = 0.05）：只有当先证者为女性时，发病年龄早才会影响其兄弟姐妹的风险。未发现家族中受影响亲属的数量会影响兄弟姐妹的风险，但检验效能不足（95%可信区间为0.50 - 2.62）。这一结果与一个具有极低外显率的单一显性基因相符，该模型作为MS可能的遗传模式尚未被推翻。
