脂蛋白酯酶基因突变与肥胖儿童心血管疾病危险的研究

关玉明; 桂永浩; 罗飞宏; 沈水仙; 杨毅

PDF(1057 KB)

中国当代儿科杂志 ›› 2010, Vol. 12 ›› Issue (3) : 161-164.

论著·临床研究

脂蛋白酯酶基因突变与肥胖儿童心血管疾病危险的研究

关玉明，桂永浩，罗飞宏，沈水仙，杨毅

作者信息 +

Lipoprotein lipase gene mutations and the risk of cardiovascular diseases in children with obesity

GUAN Yu-Ming, GUI Yong-Hao, LUO Fei-Hong, SHEN Shui-Xian, YANG Yi

Author information +

文章历史 +

摘要

目的：了解脂蛋白酯酶基因外显子常见突变与肥胖儿童心血管疾病发生发展的关系。方法：用聚合酶链反应结合限制性片段长度多态性分析检测脂蛋白酯酶外显子常见的3个突变位点D9N、N291S和S447X，同时检测血脂。比较157例肥胖儿童与175例非肥胖儿童基因突变率的差异，以及不同基因型血脂的分布差异。结果：332名肥胖及非肥胖儿童中未检测出D9N和N291S突变，S447X突变在肥胖与非肥胖儿童中分布差异无统计学意义，S447与X447两种基因型间血脂含量差异亦无统计学意义。结论：D9N与N291S基因突变可能不是引起肥胖儿童心血管疾病的危险因素，S447X突变对肥胖儿童心血管疾病的发展影响不大。［中国当代儿科杂志，2010，12（3）：161-164］

Abstract

OBJECTIVE: To inquire into the relationship between lipoprotein lipase (LPL) gene D9N, N291S and S447X polymorphisms and the development of cardiovascular diseases in children with obesity. METHODS: The polymerase chain reaction (PCR) and restriction fragment length polymorphism (RLFP) techniques were used to detect three common mutations of LPL gene exon D9N, N291S and S447X in 157 obese children and 175 normal controls. Plasma lipid and lipoprotein levels between children with different genotypes were compared. RESULTS: The D9N and N291S gene mutations were not detected in either the obese or the control groups. There were no significant differences in the frequency of S447X gene mutation between the two groups. There were no significant differences in the levels of plasma lipid and lipoprotein between children with S447 and X447 genotypes. CONCLUSIONS: D9N and N291S gene mutations may not be risk factors associated with cardiovascular diseases in children with obesity. S447X gene mutation might not play an important role in the development of cardiovascular diseases in childhood.［Chin J Contemp Pediatr, 2010, 12 (3):161-164］

导出引用

关玉明, 桂永浩, 罗飞宏, 沈水仙, 杨毅. 脂蛋白酯酶基因突变与肥胖儿童心血管疾病危险的研究[J]. 中国当代儿科杂志. 2010, 12(3): 161-164

GUAN Yu-Ming, GUI Yong-Hao, LUO Fei-Hong, SHEN Shui-Xian, YANG Yi. Lipoprotein lipase gene mutations and the risk of cardiovascular diseases in children with obesity[J]. Chinese Journal of Contemporary Pediatrics. 2010, 12(3): 161-164

中图分类号： R723

参考文献

［1］Stettler N, Zemel BS, Kumanyika S, Stallings VA. Infant weight gain and childhood overweight status in a multicenter, cohort study［J］. Pediatrics, 2002, 109(2):194-199.
［2］Berenson GS, Srinivasan SR, Bao W, Newman WP 3rd, Tracy RE, Wattigney WA. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study［J］. N Engl J Med, 1998, 338(23):1650-1656.
［3］Santamarina-Fojo S, Dugi KA. Structure, function and role of lipoprotein lipase in lipoprotein metabolism［J］. Curr Opin Lipidol, 1994, 5(2):117-125.
［4］Oka K, Tkalcevic GT, Nakano T, Tucker H, Ishimura-Oka K, Brown WV. Structure and polymorphic map of human lipoprotein lipase gene［J］. Biochim Biophys Acta, 1990, 1049(1):21-26.
［5］Humphries SE, Nicaud V, Margalef J, Tiret L, Talmud PJ. Lipoprotein lipase gene variation is associated with a paternal history of premature coronary artery disease and fasting and postprandial plasma triglycerides: the European Atherosclerosis Research Study (EARS)［J］. Arterioscler Thromb Vasc Biol, 1998, 18(4):526-534.
［6］中国肥胖问题工作组.中国学龄儿童青少年超重、肥胖筛查体重指数值分类标准［J］.中华流行病学杂志, 2004, 25(2):97-102.
［7］Fisher RM, Humphries SE, Talmud PJ. Common variation in the lipoprotein lipase gene: effects on plasma lipids and risk of atherosclerosis［J］. Atherosclerosis, 1997, 135(2):145-159.
［8］Gerdes C, Fisher RM, Nicaud V, Boer J, Humphries SE, Talmud PJ, et al. Lipoprotein lipase variants D9N and N291S are associated with increased plasma triglyceride and lower high-density lipoprotein cholesterol concentrations: studies in the fasting and postprandial states: the European Atherosclerosis Research Studies［J］. Circulation, 1997, 96(3):733-740.
［9］Mailly F, Tugrul Y, Reymer PW, Bruin T, Seed M, Groenemeyer BF, et al. A common variant in the gene for lipoprotein lipase (Asp9→Asn). Functional implications and prevalence in normal and hyperlipidemic subjects［J］. Arterioscler Thromb Vasc Biol, 1995, 15(4):468-478.
［10］Fisher RM, Mailly F, Peacock RE, Hamsten A, Seed M, Yudkin JS, et al. Interaction of the lipoprotein lipase asparagine 291→serine mutation with body mass index determines elevated plasma triacylglycerol concentrations: a study in hyperlipidemic subjects, myocardial infarction survivors, and healthy adults［J］. J Lipid Res, 1995, 36(10):2104-2112.
［11］Jukema JW, van Boven AJ, Groenemeijer B, Zwinderman AH, Reiber JH, Bruschke AV, et al. The Asp9 Asn mutation in the lipoprotein lipase gene is associated with increased progression of coronary atherosclerosis. REGRESS Study Group, Interuniversity Cardiology Institute, Utrecht, The Netherlands. Regression Growth Evaluation Statin Study［J］. Circulation, 1996, 94(8):1913-1918.
［12］Wittrup HH, Tybjaerg-Hansen A, Abildgaard S, Steffensen R, Schnohr P, Nordestgaard BG. A common substitution (Asn291Ser) in lipoprotein lipase is associated with increased risk of ischemic heart disease［J］. J Clin Invest, 1997, 99(7):1606-1613.
［13］Chen W, Srinivasan SR, Elkasabany A, Ellsworth DL, Boerwinkle E, Berenson GS. Influence of lipoprotein lipase serine 447 stop polymorphism on tracking of triglycerides and HDL cholesterol from childhood to adulthood and familial risk of coronary artery disease: the Bogalusa Heart Study［J］. Atherosclerosis, 2001, 159(2):367-373.
［14］Snieder H, van Doornen LJP, Boomsma DI. Dissecting the genetic architecture of lipids, lipoproteins, and apolipoproteins: lessons from twin studies［J］. Arterioscler Thromb Vasc Biol, 1999, 19(12):2826-2834.
［15］Jarvik GP, Goode EL, Austin MA, Auwerx J, Deeb S, Schellenberg GD, et al. Evidence that the apolipoprotein E-genotype effects on lipid levels can change with age in males: a longitudinal analysis［J］. Am J Hum Genet, 1997, 61(1):171-181.
［16］Sawano M, Watanabe Y, Ohmura H, Shimada K, Daida H, Mokuno H, et al. Potentially protective effects of the Ser447-Ter mutation of the lipoprotein lipase gene against the development of coronary artery disease in japanese subjects via a beneficial lipid profile［J］. Jpn Circ J, 2001, 65(4):310-314.