TY - JOUR
T1 - A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia
AU - Huertas-Vazquez, Adriana
AU - Plaisier, Christopher L.
AU - Geng, Ruishuang
AU - Haas, Blake E.
AU - Lee, Jenny
AU - Greevenbroek, Marleen M.
AU - Van Der Kallen, Carla
AU - De Bruin, Tjerk W.A.
AU - Taskinen, Marja Riitta
AU - Alagramam, Kumar N.
AU - Pajukanta, Päivi
N1 - Funding Information:
assistance. C. L. Plaisier is supported by the National Human Genome Research Institute grant T32 HG02536. M.-R. Taskinen is supported by a grant from Finnish Heart Foundation. This research was supported by the National Institutes of Health grant HL-28481 and the American Heart Association grant 0725232Y. T. W. A. de Bruin has been employed by GlaxoSmithKline. This work was not supported in full or part by GlaxoSmithKline. We would like to thank Janis Paulsey in the laboratory of K. Alagramam for technical assistance with animal work.
PY - 2010/1
Y1 - 2010/1
N2 - Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by the presence of multiple lipoprotein phenotypes that increase the risk of premature coronary heart disease. In a previous study, we identified an intragenic microsatellite marker within the protocadherin 15 (PCDH15) gene to be associated with high triglycerides (TGs) in Finnish dyslipidemic families. In this study we analyzed all four known nonsynonymous SNPs within PCDH15 in 1,268 individuals from Finnish and Dutch multigenerational families with FCHL. Association analyses of quantitative traits for SNPs were performed using the QTDT test. The nonsynonymous SNP rs10825269 resulted in a P = 0.0006 for the quantitative TG trait. Additional evidence for association was observed with the same SNP for apolipoprotein B levels (apo-B) (P = 0.0001) and total cholesterol (TC) levels (P = 0.001). None of the other three SNPs tested showed a signiWcant association with any lipid-related trait. We investigated the expression of PCDH15 in diVerent human tissues and observed that PCDH15 is expressed in several tissues including liver and pancreas. In addition, we measured the plasma lipid levels in mice with loss-of-function mutations in Pcdh15 (Pcdh15av-Tg and Pcdh15av-3J) to investigate possible abnormalities in their lipid proWle. We observed a signiWcant difference in plasma TG and TC concentrations for the Pcdh15av-3J carriers when compared with the wild type (P = 0.013 and P = 0.044, respectively). Our study suggests that PCDH15 is associated with lipid abnormalities.
AB - Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by the presence of multiple lipoprotein phenotypes that increase the risk of premature coronary heart disease. In a previous study, we identified an intragenic microsatellite marker within the protocadherin 15 (PCDH15) gene to be associated with high triglycerides (TGs) in Finnish dyslipidemic families. In this study we analyzed all four known nonsynonymous SNPs within PCDH15 in 1,268 individuals from Finnish and Dutch multigenerational families with FCHL. Association analyses of quantitative traits for SNPs were performed using the QTDT test. The nonsynonymous SNP rs10825269 resulted in a P = 0.0006 for the quantitative TG trait. Additional evidence for association was observed with the same SNP for apolipoprotein B levels (apo-B) (P = 0.0001) and total cholesterol (TC) levels (P = 0.001). None of the other three SNPs tested showed a signiWcant association with any lipid-related trait. We investigated the expression of PCDH15 in diVerent human tissues and observed that PCDH15 is expressed in several tissues including liver and pancreas. In addition, we measured the plasma lipid levels in mice with loss-of-function mutations in Pcdh15 (Pcdh15av-Tg and Pcdh15av-3J) to investigate possible abnormalities in their lipid proWle. We observed a signiWcant difference in plasma TG and TC concentrations for the Pcdh15av-3J carriers when compared with the wild type (P = 0.013 and P = 0.044, respectively). Our study suggests that PCDH15 is associated with lipid abnormalities.
UR - http://www.scopus.com/inward/record.url?scp=77449139212&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77449139212&partnerID=8YFLogxK
U2 - 10.1007/s00439-009-0749-z
DO - 10.1007/s00439-009-0749-z
M3 - Article
C2 - 19816713
AN - SCOPUS:77449139212
VL - 127
SP - 83
EP - 89
JO - Human Genetics
JF - Human Genetics
SN - 0340-6717
IS - 1
ER -
