ELMOD2 is a candidate gene for familial idiopathic pulmonary fibrosis.
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.
Hodgson
Ulla
U
Department of Pulmonary Medicine, Helsinki University Central Hospital, Finland. ulla.hodgson@hus.fi.
Pulkkinen
Ville
V
Dixon
Morag
M
Peyrard-Janvid
Myriam
M
Rehn
Marko
M
Lahermo
Paivi
P
Ollikainen
Vesa
V
Salmenkivi
Kaisa
K
Kinnula
Vuokko
V
Kere
Juha
J
Tukiainen
Pentti
P
Laitinen
Tarja
T
D002894:Chromosomes, Human, Pair 4; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D011658:Pulmonary Fibrosis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
D003598:Cytoskeletal Proteins; C512339:ELMOD2 protein, human; D012333:RNA, Messenger