Abstract
To elucidate the mechanism of lipid metabolism in the genesis of essential hypertension (EH), we linked blood pressure (BP) phenotypes with the lipoprotein lipase (LPL) gene. Variance component and sib-pair linkage models were used to test the relationship of the polymorphisms in the LPL gene region and EH in 148 Chinese hypertensive families. Linkage evidence with systolic BP (SBP) and diastolic BP (DBP) was observed in a total population of 148 pedigrees with seven flanking microsatellite markers of the LPL gene, with a maximum two-point LOD score of 2.68 and a maximum multipoint LOD score (MLS) of 2.37 for SBP and a maximum MLS of 1.54 for DBP. Suggestive linkage results around this region were also obtained in northern and southern subsets by geographic distribution. In addition, quantitative-transmission/disequilibrium-test analyses showed that there was linkage between DBP and two single nucleotide polymorphisms in the LPL gene. This is the first report of linkage between LPL gene and DBP in the Chinese population. The LPL gene itself might explain our results or the LPL gene region might harbor some genes to explain the observed results to some degree and might contribute to the variation of BP in the Chinese population.
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References
Abecasis GR, Cardon LR, Cookson WOC (2000) A general test of association for quantitative traits in nuclear families. Am J Hum Genet 66:279–292
Allayee H, Bruin TWA de, Dominguez KM, Cheng LSC, Ipp E, Cantor RM, Krass KL, Keulen ETP, Aouizerat BE, Lusis AJ, Rotter JI (2001) Genome scan for blood pressure in Dutch dyslipidemic families reveals linkage to a locus on chromosome 4p. Hypertension 38:773–778
Almasy L, Blangero J (1998) Multipoint quantitative trait linkage analysis in general pedigrees. Am J Hum Genet 62:1198–1211
An P, Rice T, Gagnon J, Borecki IB, Perusse L, Leon AS, Skinner JS, Wilmore JH, Bouchard C, Rao DC (1999) Familial aggregation of resting blood pressure and heart rate in a sedentary population: the Heritage Study. Am J Hypertens 12:264–270
Cantor RM, Davis RC, Hsueh WA, Raffel LR, Buchanan TA, Saad MF (1997) Linkage of systolic blood pressure to the lipoprotein lipase for the pleiotropic effect of a gene contributing to the metabolic syndrome (abstract). Am J Hum Genet 61:A270
Chu S, Zhu D, Xiong M, Wang GL, Jin L (2001) Linkage analysis of candidate genes for glucose and lipid metabolism with essential hypertension. Natl Med J China 81:20–22
Fuh MM, Shieh SM, Wu DA, Chen YD, Reaven GM (1987) Abnormalities of carbohydrate and lipid metabolism in patients with hypertension. Arch Intern Med 147:1035–1038
Groenemeijer BE, Hallman MD, Reymer PW, Gagne E, Kuivenhoven JA, Bruin T, Jansen H, Lie KI, Bruschke AV, Boerwinkle E, Hayden MR, Kastelein JJP(1997) Genetic variant showing a positive interaction with beta-blocking agents with a beneficial influence on lipoprotein lipase activity, HDL cholesterol, and triglyceride levels in coronary artery disease patients. The Ser447-stop substitution in the lipoprotein lipase gene. Circulation 95:2628–2635
Henderson HE, Kastelein JJ, Zwinderman AH, Gagne E, Jukema JW, Reymer PWA, Groenemeyer BE, Lie KI, Bruschke AV, Hayden MR, Jansen H (1999) Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins. J Lipid Res 40:735–743
Julius S, Jamerson K, Mejia A, Krause L, Schork N, Jones K (1990) The association of borderline hypertension with target organ changes and higher coronary risk: Tecumseh blood pressure study. JAMA 264:354–358
MacMahon SW, Macdonald GJ, Blacket RB (1985) Plasma lipoprotein levels in treated and untreated hypertensive men and women. Arteriosclerosis 5:391–396
Mamputu JC, Renier G (1999) Differentiation of human monocytes to monocyte-derived macrophages is associated with increased lipoprotein lipase-induced tumor necrosis factor-alpha expression and production. Arterioscler Thromb Vasc Biol 19:1405–1411
Pan WH, Chen YC, Yu SL, Sun JA, Chang YS, Chen CJ (1994) Correlates and predictive models for blood pressure values in residents of two communities in Taiwan. J Formos Med Assoc 93:582–591
Pan WH, Chen JW, Fann C, Jou YS, Wu SY (2000) Linkage analysis with candidate genes: the Taiwan young-onset hypertension genetic study. Hum Genet 107:210–215
Pentikainen MO, Oksjoki R, Oorni K, Kovanen PT (2002) Lipoprotein lipase in the arterial wall. Arterioscler Thromb Vasc Biol 22:211–217
Povey S, Lovering R, Bruford E, Wright M, Lush M, Wain H (2001) The HUGO gene nomenclature committee (HGNC). Hum Genet 109:678–680
Rao DC (2001) Genetic dissection of complex traits: an overview. In: Rao DC, Province MA (eds) Genetic dissection of complex traits, vol 2. Academic Press, San Diego, pp 13–34
Razzaghi H, Aston CE, Hamman RF, Kamboh MI (2000) Genetic screening of the lipoprotein lipase gene for mutations associated with high triglyceride/low HDL-cholesterol levels. Hum Genet 107:256–267
Renier G, Skamene E, DeSanctis JB, Radzioch D (1994) Induction of tumor necrosis factor alpha gene expression by lipoprotein lipase. J Lipid Res 35:271–278
S.A.G.E. (2001) Statistical Analysis for Genetic Epidemiology, release 4.0. Computer program package available from the Department of Epidemiology and Biostatistics, Rammelkamp Center for Education and Research, MetroHealth Campus, Case Western Reserve University
Safar ME, Frohlich ED (1995) The arterial system in hypertension. A prospective view. Hypertension 26:10–14
Sass C, Herbeth B, Siest G, Visvikis S (2000) Lipoprotein lipase (C/G)447 polymorphism and blood pressure in the Stanislas cohort. J Hypertens 18:1775–1781
Williams RR, Hunt SC, Hopkins PN, Stults BM, Wu LL, Hasstedt SJ, Barlow GK, Stephenson SH, Lalouel JM, Kuida H (1988) Familial dyslipidemic hypertension: evidence from 58 Utah families for a syndrome present in approximately 12% of patients with essential hypertension. JAMA 259:3579–3586
Williams RR, Hunt SC, Hasstedt SJ, Hopkins PN, Wu LL, Berry TD, Stults BM, Barlow GK, Schumacher C, Lifton RP, Lalouel JM (1991) Are there interactions and relations between genetic and environmental factors in predisposing to high blood pressure? Hypertension 18 (Suppl I):I29–I37
Wittrup HH, Tybjaerg-Hansen A, Nordestgaard BG (1999) Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease: a meta-analysis. Circulation 99:2901–2907
Wu DA, Bu XD, Warden CH, Shen DDC, Jeng CY, Sheu WHH, Fuh MMT, Katsuya T, Dzau VJ, Reaven GM, Lusis AJ, Rotter JI, Chen YDI (1996) Quantitative trait locus mapping of human blood pressure to a genetic region at or near the lipoprotein lipase gene locus on chromosome 8p22. J Clin Invest 97:2111–2118
Acknowledgements
This work was funded by grants 2002BA711A05, 2002BA711A08 and 2002BA711A10 of The National Tenth Five-Year Plan Key Programs from the Ministry of Science and Technology of the People’s Republic of China and the H020220030130 Biomedical Project from the Council of Science and Technology, Beijing. Most of the laboratory work was completed in the Chinese National Human Genome Center, Beijing. Some of the results of the sib-pair linkage analysis were obtained by use of the program package S.A.G.E., which is supported by a US Public Health Service Resource grant (RR03655) from the National Center for Research Resources; some results were obtained by means of SOLAR and QTDT.
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Yang, W., Huang, J., Ge, D. et al. Lipoprotein lipase gene is in linkage with blood pressure phenotypes in Chinese pedigrees. Hum Genet 115, 8–12 (2004). https://doi.org/10.1007/s00439-004-1108-8
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DOI: https://doi.org/10.1007/s00439-004-1108-8