ELMOD2 Is a Candidate Gene for Familial Idiopathic Pulmonary Fibrosis

Abstract

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.

Molecular biomarkers in idiopathic pulmonary fibrosis

“…Genome-wide linkage scanning of six multiplex FPF families from southeastern Finland, an area with clustering of FPF due to common ancestry, identified mutations in ELMOD2 (ELMO domain containing 2) that was associated with decreased ELMOD2 mRNA expression in the lung (31). In the lung, ELMOD2 is expressed in macrophages and type II AECs.…”

Spatial and temporal variability of idiopathic pulmonary fibrosis cases in Silesian Voivodeship in years 2006–2010

“…Etiology of idiopathic pulmonary fibrosis is unknown as for now, but the following factors contributing pulmonary fibrosis are enumerated: some drugs and chemotherapeutic agents [5][6][7], X-ray therapy, exposure to tobacco smoke [8][9][10], occupational exposure to organic dust (e.g., textile fiber, wood dust) or inorganic dusts (e.g., mineral or metallic) [10][11][12][13], viral or bacterial lung infections, the occurrence of gastro-oesophageal reflux [9,10], age and genetic predisposition [1,9,10,12,14,15]. According to the report of the European Lung White Book, real incidence of idiopathic pulmonary fibrosis remains unknown [16].…”

Comorbidity diseases in adults with diagnosed interstitial lung diseases among inhabitants of the Silesian voivodeship, Poland

“…Wśród czynników sprzyjających zachorowaniu wymienia się ekspozycję na pyły organiczne i nieorganiczne [6][7][8], zanieczyszczenia środowiska mykobakteriami [9], narażenie na czynniki chemiczne, gazy, pary, promieniowanie jonizujące, stosowanie leków lub substancji psychoaktywnych [10][11][12], ekspozycję na dym tytoniowy [13][14], wirusowe lub bakteryjne zakażenia płuc, występowanie refluksu żołądkowo-przełykowe-go [14] oraz wiek i predyspozycje genetyczne [7,[15][16][17]. Tylko jednak w co 3. przypadku chorób śródmiąższo-wych płuc możliwe jest ustalenie etiologii [18].…”