Familial Interstitial Pneumonia (FIP) is linked to Chromosomes 10, 11 and 12. M.C. Speer1, L.H. Burch2, M.P. Steele1,2, A. Herron1, J.E. Loyd3, K.K. Brown4, J.A. Phillips III3, A. Wise2, S.H. Slifer1, C.F. Potocky1, M.I. Schwarz4, D.A. Schwartz1,2 1) Duke Univ Medical Ctr, Durham, NC; 2) National Institute of Environmental Health Sciences, Research Triangle Park, NC; 3) Vanderbilt University School of Medicine, Nashville, TN; 4) National Jewish Medical and Research Center and University of Colorado Health Science Center, Denver, CO.
The idiopathic interstitial pneumonias (IIP) are a clinically heterogeneous group of fibrosing interstitial lung diseases that lead to hypoxemic respiratory insufficiency with both genetic and environmental contributions to etiology. The most common IIP is usual interstitial pneumonia (UIP), the underlying histology of idiopathic pulmonary fibrosis(IPF). Typically, IPF (OMIM178500) presents in late life and is lethal within 4-5 years of diagnosis. Treatment options, apart from lung transplantation, are limited and do not appear to prolong survival. Identifying the genetic basis for this condition will lead to earlier identification and enhanced interventions. We performed a genomic screen using 890 microsatellite repeat markers spaced at an average 4.1 cM including 82 families with 2 members with probable/definite IIP. We identified a maximum multipoint lod score of 3.03 at D11S1318, incorporating a 16.4 cM region bounded by D11S4046 and D11S4149. A second linkage peak spans 15 cM and is bounded by D10S1751 and D10S1664 (maximum multipoint LOD score of 2.27 at D10S1649). Families with fewer than 67% smokers among affected individuals contributed significantly to evidence for linkage at 11pter (p=0.01; maximum lod = 4.58). The 82 families were subdivided into those with only IPF-type disease [homogeneous familial interstitial pneumonia - FIP] and families with 1 case of IPF and one other type of IIP [heterogenous FIP]. When considered alone, the homogeneous families identified a region of interest at D12S368 (maximum multipoint lod score 1.89). In summary, we identified regions on chromosomes 10, 11, and 12 that likely contain genes contributing to FIP. Moreover, our findings indicate that linkage on chromosome 11 is influenced by cigarette smoking and that linkage on chromosome 12 is influenced by disease phenotype.