Oturai Annette Bang, Ryder Lars P, Fredrikson Sten, Myhr Kjell-Morten, Celius Elisabeth G, Harbo Hanne Flinstad, Andersen Oluf, Akesson Eva, Hillert Jan, Madsen Hans O, Nyland Harald, Spurkland Anne, Datta Pameli, Svejgaard Arne, Sorensen Per S
Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Mult Scler. 2004 Feb;10(1):5-8. doi: 10.1191/1352458504ms975oa.
Investigation of coaffected sib pairs is one method to determine the genetic influence on the clinical presentation of many complex diseases, such as multiple sclerosis (MS). Investigation of the clinical concordance in coaffected sib pairs may be a prerequisite to identify genes that modify the clinical outcome. The aim of this study was to investigate a possible genetic influence on selected demographic and clinical variables among familial Scandinavian MS cases.
We identified 136 Caucasian Scandinavian families with MS coaffected sib pairs from Denmark, Norway and Sweden. Cohen's kappa coefficient and the intraclass correlation coefficient were used to assess concordances in sib pairs. Furthermore, clinical features and HLA-DR2 carrier status were compared among the probands of sib pairs.
We found significant concordance of the disease course (kappa = 0.28, P < 0.001) and adjusted age of onset (r = 0.23, P = 0.028). Among probands of sib pairs, HLA-DR2 carrier patients had a younger age of onset (P = 0.024).
Analyses of Scandinavian coaffected sib pairs suggest that disease course and age of onset are partly under genetic control. Furthermore, HLA-DR2 in probands of sib pairs suggests importance for age of onset.
对共同患病的同胞对进行研究是确定遗传因素对许多复杂疾病(如多发性硬化症,MS)临床表现影响的一种方法。研究共同患病的同胞对之间的临床一致性可能是识别影响临床结局基因的先决条件。本研究的目的是调查斯堪的纳维亚家族性MS病例中选定的人口统计学和临床变量可能受到的遗传影响。
我们从丹麦、挪威和瑞典确定了136个患有MS的共同患病同胞对的白种人斯堪的纳维亚家庭。使用科恩kappa系数和组内相关系数来评估同胞对之间的一致性。此外,还比较了同胞对先证者的临床特征和HLA-DR2携带者状态。
我们发现疾病进程(kappa = 0.28,P < 0.001)和调整后的发病年龄(r = 0.23,P = 0.028)存在显著一致性。在同胞对的先证者中,携带HLA-DR2的患者发病年龄较小(P = 0.024)。
对斯堪的纳维亚共同患病同胞对的分析表明,疾病进程和发病年龄部分受遗传控制。此外,同胞对先证者中的HLA-DR2表明其对发病年龄具有重要性。