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Primary pulmonary hypertension may be a heterogeneous disease with a second locus on chromosome 2q31

Matthias Rindermann^*, Ekkehard Grünig, MD, Albrecht von Hippel^*, Rolf Koehler, PhD^*, Gabriel Miltenberger-Miltenyi, MD, PhD^*, Derliz Mereles, MD, Karlin Arnold, Michael Pauciulo, William Nichols, PhD, Horst Olschewski, MD, Marius M. Hoeper, MD^||, J.örg Winkler, MD^¶, Hugo A. Katus, MD, Wolfgang Kübler, MD, FRCP, Claus R. Bartram, MD^* and Bart Janssen, PhD^*,*

^* Institute of Human Genetics, Heidelberg, Germany
Department of Cardiology, University of Heidelberg, Heidelberg, Germany
Department of Pneumology, University of Giessen, Giessen, Germany
Division of Human Genetics, Children’s Hospital Medical Center, Cincinnati, Ohio, USA
^|| Department of Pneumology, University of Hannover, Hannover, Germany
^¶ Department of Pneumology, University of Leipzig, Leipzig, Germany

View larger version (18K): [in a new window]   Figure 1 Results of the multipoint linkage analysis for the 10 primary pulmonary hypertension families on chromosome 2q31-q33. The thin line (Z) indicates the cumulative lod scores assuming homogeneity. The thick line indicates the maximum lod score when allowing for heterogeneity (Z(het)max). Indicated above the x-axis are the map positions of the markers. Also indicated is the map position of the bone morphogenetic protein receptor type 2 gene (BMPR2) locus.

View larger version (37K): [in a new window]   Figure 2 Haplotypes of the PPH2 families: 965, 1893, and 2135. Filled symbols = manifest primary pulmonary hypertension (PPH); half-filled symbols = abnormal pulmonary artery systolic pressure (PASP) response to exercise (>40 mm Hg) (AR). The risk haplotypes are shown in black.