A lipid-lowering gene exists on chromosome 13q. H. Knoblauch¹, B. Mueller-Myhsok², A. Busjahn¹, L. Ben Avi³, S. Baehring¹, H. Baron¹, S. Heath⁴, H.D. Faulhaber¹, S. Shpitzen³, A. Aydin¹, A. Reshef³, R. Uhlmann¹, M. Rosenthal¹, O. Eliav³, D. Schurr¹, A. Lowe⁵, Y. Friedlander³, H. Schuster¹, F.C. Luft¹, E. Leitersdorf³. 1) Franz Volhard Clinic and Max Delbrueck Center for Molecular Medicine, Berlin, Germany; 2) Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany; 3) Center for Research, Prevention and Treatment of Atherosclerosis, and Department of Social Medicine, Hadassah University Hospital and School of Public Health, Jerusalem, Israel; 4) Laboratory of Statistical Genetics, Rockefeller University, New York; 5) Applied Biosystems Inc., Foster City, CA.

   A lipid-lowering gene has been postulated from familial hypercholesterolemia (FH) families having heterozygous persons with normal LDL levels and homozygous individuals with LDL levels similar to heterozygous FH persons. We studied such an FH family which also had non-FH members with lower than normal LDL levels. We performed linkage analyses and identified a locus at 13q defined by markers D13S154 and D13S158. FASTLINK and GENEHUNTER yielded LOD scores >4, while an affected sibpair analysis yielding a peak multipoint LOD of 4.82, corresponding to a p value of 1.26x10-6. A multipoint quantitative-trait (QTL) linkage analysis with MLBQTL verified this locus as a QTL for LDL levels. To test the relevance of this QTL in an independent normal population, we studied monozygotic (MZ) and dizygotic (DZ) twin subjects. An MZ-DZ comparison confirmed genetic variance on lipid concentrations. We then performed an IBD linkage analysis on the DZ twins and their parents with markers at the 13q locus. We found strong evidence for linkage at this locus with LDL (p<0.0002), HDL (p<0.004), total cholesterol (p<0.0002), and body mass index (p<0.0001). These data provide support for the existence of a new gene influencing lipid concentrations in normal man.