A locus on chromosome 10 influences C-reactive protein levels in two independent populations

Ulrich Broeckel; Christian Hengstenberg; Bjoern Mayer; Karen Maresso; Daniel Gaudet; Ondrej Seda; Johanne Tremblay; Stephan Holmer; Jeanette Erdmann; Christian Glöckner; Michael Harrison; Lisa J. Martin; Jeff T. Williams; Gerd Schmitz; Guenter A.J. Riegger; Howard J. Jacob; Pavel Hamet; Heribert Schunkert

doi:10.1007/s00439-007-0380-9

A locus on chromosome 10 influences C-reactive protein levels in two independent populations

Ulrich Broeckel^*, Christian Hengstenberg, Bjoern Mayer, Karen Maresso, Daniel Gaudet, Ondrej Seda, Johanne Tremblay, Stephan Holmer, Jeanette Erdmann, Christian Glöckner, Michael Harrison, Lisa J. Martin, Jeff T. Williams, Gerd Schmitz, Guenter A.J. Riegger, Howard J. Jacob, Pavel Hamet, Heribert Schunkert

^*Korrespondierende/r Autor/-in für diese Arbeit

Medizinische Klinik II

9 Zitate (Scopus)

Abstract

High sensitivity C-reactive protein (hsCRP) is an independent risk factor for cardiovascular disease, such as stroke or coronary artery disease. Genetic factors influence significantly the inter-individual variability of hsCRP. The aim of this study was to identify genomic regions influencing hsCRP levels. A genome scan was performed in two independent studies of Caucasian populations, namely 513 Western-European families ascertained for myocardial infarction (n = 1,406) and 120 French-Canadian families diagnosed with hypertension (n = 758). In the myocardial infarction families, 31% of the inter-individual variation of hsCRP levels was explained by genetic factors (P = 0.0000015) and loci influencing hsCRP were identified on chromosomes 10 (at 141 cM) and 5 (at 150 cM) with multipoint LOD scores of 3.15 and 2.23, respectively. An additional suggestive signal was detected on chromosome 2 in subset analyses. A similar degree of heritability has been observed in a second independent population of French-Canadian hypertensive families for hsCRP (30%) and linkage results for chromosome 10 were confirmed with maximum LOD score of 2.7. We identified a chromosomal region in two independent populations which influences hsCRP in addition to several unique regions. This provides targets for the identification of genes involved in the regulation of hsCRP and the development and progression of vascular disease, including stroke.

Originalsprache	Englisch
Zeitschrift	Human Genetics
Jahrgang	122
Ausgabenummer	1
Seiten (von - bis)	95-102
Seitenumfang	8
ISSN	0340-6717
DOIs	https://doi.org/10.1007/s00439-007-0380-9
Publikationsstatus	Veröffentlicht - 01.08.2007

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Acknowledgments We thank the members of the families for their participation. Moreover, we thank Ms Daniela Hant; B.S., for expert technical assistance and Alexandru Gurau and Pierre-Luc Brunelle for bioinformatics assistance. U.B. and H.J.J. are supported in part by a grants from NHLBI (1P50 HL65203; 1R01 HL 74321). Moreover, we acknowledge the support by the Wilhelm-Vaillant-Stiftung, the Deutsche Herzstiftung, the National Genome Network (NGFN) of the Bun-desministerium für Bildung und Forschung, the Cullen Family Run (U.B.), and the Deutsche Forschungsgemeinschaft (C.H., S.H., J.E., and H.S.). The statistical genetic analyses reported here were conducted using the program package SOLAR. SOLAR is supported by U.S. Public Health Service grant MH059490 from the National Institutes of Health.

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Broeckel, U., Hengstenberg, C., Mayer, B., Maresso, K., Gaudet, D., Seda, O., Tremblay, J., Holmer, S., Erdmann, J., Glöckner, C., Harrison, M., Martin, L. J., Williams, J. T., Schmitz, G., Riegger, G. A. J., Jacob, H. J., Hamet, P., & Schunkert, H. (2007). A locus on chromosome 10 influences C-reactive protein levels in two independent populations. Human Genetics, 122(1), 95-102. https://doi.org/10.1007/s00439-007-0380-9

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title = "A locus on chromosome 10 influences C-reactive protein levels in two independent populations",

abstract = "High sensitivity C-reactive protein (hsCRP) is an independent risk factor for cardiovascular disease, such as stroke or coronary artery disease. Genetic factors influence significantly the inter-individual variability of hsCRP. The aim of this study was to identify genomic regions influencing hsCRP levels. A genome scan was performed in two independent studies of Caucasian populations, namely 513 Western-European families ascertained for myocardial infarction (n = 1,406) and 120 French-Canadian families diagnosed with hypertension (n = 758). In the myocardial infarction families, 31\% of the inter-individual variation of hsCRP levels was explained by genetic factors (P = 0.0000015) and loci influencing hsCRP were identified on chromosomes 10 (at 141 cM) and 5 (at 150 cM) with multipoint LOD scores of 3.15 and 2.23, respectively. An additional suggestive signal was detected on chromosome 2 in subset analyses. A similar degree of heritability has been observed in a second independent population of French-Canadian hypertensive families for hsCRP (30\%) and linkage results for chromosome 10 were confirmed with maximum LOD score of 2.7. We identified a chromosomal region in two independent populations which influences hsCRP in addition to several unique regions. This provides targets for the identification of genes involved in the regulation of hsCRP and the development and progression of vascular disease, including stroke.",

author = "Ulrich Broeckel and Christian Hengstenberg and Bjoern Mayer and Karen Maresso and Daniel Gaudet and Ondrej Seda and Johanne Tremblay and Stephan Holmer and Jeanette Erdmann and Christian Gl{\"o}ckner and Michael Harrison and Martin, \{Lisa J.\} and Williams, \{Jeff T.\} and Gerd Schmitz and Riegger, \{Guenter A.J.\} and Jacob, \{Howard J.\} and Pavel Hamet and Heribert Schunkert",

year = "2007",

month = aug,

day = "1",

doi = "10.1007/s00439-007-0380-9",

language = "English",

volume = "122",

pages = "95--102",

journal = "Human Genetics",

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publisher = "Oxford University Press",

number = "1",

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Broeckel, U, Hengstenberg, C, Mayer, B, Maresso, K, Gaudet, D, Seda, O, Tremblay, J, Holmer, S, Erdmann, J, Glöckner, C, Harrison, M, Martin, LJ, Williams, JT, Schmitz, G, Riegger, GAJ, Jacob, HJ, Hamet, P & Schunkert, H 2007, 'A locus on chromosome 10 influences C-reactive protein levels in two independent populations', Human Genetics, Jg. 122, Nr. 1, S. 95-102. https://doi.org/10.1007/s00439-007-0380-9

TY - JOUR

T1 - A locus on chromosome 10 influences C-reactive protein levels in two independent populations

AU - Broeckel, Ulrich

AU - Hengstenberg, Christian

AU - Mayer, Bjoern

AU - Maresso, Karen

AU - Gaudet, Daniel

AU - Seda, Ondrej

AU - Tremblay, Johanne

AU - Holmer, Stephan

AU - Erdmann, Jeanette

AU - Glöckner, Christian

AU - Harrison, Michael

AU - Martin, Lisa J.

AU - Williams, Jeff T.

AU - Schmitz, Gerd

AU - Riegger, Guenter A.J.

AU - Jacob, Howard J.

AU - Hamet, Pavel

AU - Schunkert, Heribert

PY - 2007/8/1

Y1 - 2007/8/1

N2 - High sensitivity C-reactive protein (hsCRP) is an independent risk factor for cardiovascular disease, such as stroke or coronary artery disease. Genetic factors influence significantly the inter-individual variability of hsCRP. The aim of this study was to identify genomic regions influencing hsCRP levels. A genome scan was performed in two independent studies of Caucasian populations, namely 513 Western-European families ascertained for myocardial infarction (n = 1,406) and 120 French-Canadian families diagnosed with hypertension (n = 758). In the myocardial infarction families, 31% of the inter-individual variation of hsCRP levels was explained by genetic factors (P = 0.0000015) and loci influencing hsCRP were identified on chromosomes 10 (at 141 cM) and 5 (at 150 cM) with multipoint LOD scores of 3.15 and 2.23, respectively. An additional suggestive signal was detected on chromosome 2 in subset analyses. A similar degree of heritability has been observed in a second independent population of French-Canadian hypertensive families for hsCRP (30%) and linkage results for chromosome 10 were confirmed with maximum LOD score of 2.7. We identified a chromosomal region in two independent populations which influences hsCRP in addition to several unique regions. This provides targets for the identification of genes involved in the regulation of hsCRP and the development and progression of vascular disease, including stroke.

AB - High sensitivity C-reactive protein (hsCRP) is an independent risk factor for cardiovascular disease, such as stroke or coronary artery disease. Genetic factors influence significantly the inter-individual variability of hsCRP. The aim of this study was to identify genomic regions influencing hsCRP levels. A genome scan was performed in two independent studies of Caucasian populations, namely 513 Western-European families ascertained for myocardial infarction (n = 1,406) and 120 French-Canadian families diagnosed with hypertension (n = 758). In the myocardial infarction families, 31% of the inter-individual variation of hsCRP levels was explained by genetic factors (P = 0.0000015) and loci influencing hsCRP were identified on chromosomes 10 (at 141 cM) and 5 (at 150 cM) with multipoint LOD scores of 3.15 and 2.23, respectively. An additional suggestive signal was detected on chromosome 2 in subset analyses. A similar degree of heritability has been observed in a second independent population of French-Canadian hypertensive families for hsCRP (30%) and linkage results for chromosome 10 were confirmed with maximum LOD score of 2.7. We identified a chromosomal region in two independent populations which influences hsCRP in addition to several unique regions. This provides targets for the identification of genes involved in the regulation of hsCRP and the development and progression of vascular disease, including stroke.

UR - https://www.scopus.com/pages/publications/34447282010

U2 - 10.1007/s00439-007-0380-9

DO - 10.1007/s00439-007-0380-9

M3 - Journal articles

C2 - 17530289

AN - SCOPUS:34447282010

SN - 0340-6717

VL - 122

SP - 95

EP - 102

JO - Human Genetics

JF - Human Genetics

IS - 1

ER -

A locus on chromosome 10 influences C-reactive protein levels in two independent populations

Abstract

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