Hodgson Ulla, Pulkkinen Ville, Dixon Morag, Peyrard-Janvid Myriam, Rehn Marko, Lahermo Paivi, Ollikainen Vesa, Salmenkivi Kaisa, Kinnula Vuokko, Kere Juha, Tukiainen Pentti, Laitinen Tarja
Department of Pulmonary Medicine, Helsinki University Central Hospital, Finland.
Am J Hum Genet. 2006 Jul;79(1):149-54. doi: 10.1086/504639. Epub 2006 May 9.
We performed a genomewide scan in six multiplex families with familial idiopathic pulmonary fibrosis (IPF) who originated from southeastern Finland. The majority of the Finnish multiplex families were clustered in the region, and the population history suggested that the clustering might be explained by an ancestor shared among the patients. The genomewide scan identified five loci of interest. The hierarchical fine mapping in an extended data set with 24 families originating from the same geographic region revealed a shared 110 kb to 13 Mb haplotype on chromosome 4q31, which was significantly more frequent among the patients than in population-based controls (odds ratio 6.3; 95% CI 2.5-15.9; P = .0001). The shared haplotype harbored two functionally uncharacterized genes, ELMOD2 and LOC152586, of which only ELMOD2 was expressed in lung and showed significantly decreased messenger-RNA expression in IPF lung (n = 6) when compared with that of healthy lung (n = 7; P = .05). Our results suggest ELMOD2 as a novel candidate gene for susceptibility in familial IPF.
我们对来自芬兰东南部的六个患有家族性特发性肺纤维化（IPF）的多重家庭进行了全基因组扫描。大多数芬兰多重家庭聚集在该地区，人口历史表明这种聚集可能是由患者之间共享的祖先所解释。全基因组扫描确定了五个感兴趣的基因座。在来自同一地理区域的24个家庭的扩展数据集中进行的分层精细定位显示，4号染色体q31上有一个110 kb至13 Mb的共享单倍型，在患者中比基于人群的对照组中更为频繁（优势比6.3；95%可信区间2.5 - 15.9；P = .0001）。该共享单倍型包含两个功能未明确的基因，即ELMOD2和LOC152586，其中只有ELMOD2在肺中表达，并且与健康肺（n = 7）相比，在IPF肺（n = 6）中其信使核糖核酸表达显著降低（P = .05）。我们的结果表明ELMOD2是家族性IPF易感性的一个新的候选基因。
