A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia

Adriana Huertas-Vazquez, Christopher Plaisier, Ruishuang Geng, Blake E. Haas, Jenny Lee, Marleen M. Greevenbroek, Carla Van Der Kallen, Tjerk W.A. De Bruin, Marja Riitta Taskinen, Kumar N. Alagramam, Päivi Pajukanta

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)83-89
Number of pages7
JournalHuman Genetics
Volume127
Issue number1
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

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Familial Combined Hyperlipidemia
Single Nucleotide Polymorphism
Lipids
Triglycerides
Cholesterol
Apolipoproteins B
Microsatellite Repeats
Lipoproteins
Coronary Disease
Pancreas
Phenotype
Mutation
Liver
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Huertas-Vazquez, A., Plaisier, C., Geng, R., Haas, B. E., Lee, J., Greevenbroek, M. M., ... Pajukanta, P. (2010). A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia. Human Genetics, 127(1), 83-89. https://doi.org/10.1007/s00439-009-0749-z

A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia. / Huertas-Vazquez, Adriana; Plaisier, Christopher; Geng, Ruishuang; Haas, Blake E.; Lee, Jenny; Greevenbroek, Marleen M.; Van Der Kallen, Carla; De Bruin, Tjerk W.A.; Taskinen, Marja Riitta; Alagramam, Kumar N.; Pajukanta, Päivi.

In: Human Genetics, Vol. 127, No. 1, 01.01.2010, p. 83-89.

Research output: Contribution to journalArticle

Huertas-Vazquez, A, Plaisier, C, Geng, R, Haas, BE, Lee, J, Greevenbroek, MM, Van Der Kallen, C, De Bruin, TWA, Taskinen, MR, Alagramam, KN & Pajukanta, P 2010, 'A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia', Human Genetics, vol. 127, no. 1, pp. 83-89. https://doi.org/10.1007/s00439-009-0749-z
Huertas-Vazquez, Adriana ; Plaisier, Christopher ; Geng, Ruishuang ; Haas, Blake E. ; Lee, Jenny ; Greevenbroek, Marleen M. ; Van Der Kallen, Carla ; De Bruin, Tjerk W.A. ; Taskinen, Marja Riitta ; Alagramam, Kumar N. ; Pajukanta, Päivi. / A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia. In: Human Genetics. 2010 ; Vol. 127, No. 1. pp. 83-89.
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abstract = "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.",
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T1 - A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia

AU - Huertas-Vazquez, Adriana

AU - Plaisier, Christopher

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

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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.

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