Plasma Homocysteine and Gene Polymorphisms Associated with the Risk of Hyperlipidemia in Northern Chinese Subjects

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To examine the relationship between occurrence of hypedipidemia,plasma homocysteine and polymorphisms of methylenetetra hydrofolate reductase (MTHFR) gene and methionine synthase (MS) gene.Methods A total of 192 hyperlipidemia patients were selected and divided into hypercholesterolemia group,hypertriglyceridemia group,and combined hyperlipidemia group.Another 208 normal individuals were selected as control.Total plasma homocysteine (tHcy)concentration was measured by high-performance liquid chromatography (HPLC).Lipid profiles were measured for all subjects.The polymorphisms of MTHFR gene C677T and MS gene A2756G were analyzed by PCR-RFLP.Results The tHcy concentration in the combined hyperlipidemia patients was significantly higher than that in the control (15.95 μmol/L vs 13.43 μmol/L,P<0.05).The prevalence of hyperhomocysteinemia (Hhcy) in the combined hyperlipidemia group was significantly higher than that in the control (42.2% vs 23.0%,P=0.015),with the odds ratio (OR) of 3.339 (95%CI:1.260-8.849).The hyperlipidemia patients with Hhcy had a higher concentration of total cholesterol (TC) than that in the normal they patients (5.67±0.95 mmol/L vs 5.47±0.92 mmol/L,P=0.034).There was no significant difference in genotype or allele frequencies of MTHFR C677T between the hyperlipidemic and control groups.The hyperlipidemia patients with MTHFR CT/TT genotype had a higher concentration of triglyceride (TG) than those with CC genotype (2.24±1.75 mmol/L vs 1.87±0.95 mmol/L,P<0.05).Individuals with CT/TT genotype had a higher concentration of tHey than those with 677CC genotype both in the hyperlipidemia group (12.61±1.24 μmol/L vs 11.20±1.37 μmol/L,P<0.05) and in the control group (14.04±1.48 μmol/L vs 12.61±1.24 μmol/L,P<0.05).The percentage of MS 2756 GG/AG genotype in the combined hyperlipidemia group was significantly higher than that in the control (26.7% vs 13.0%,P=0.012),with the OR of 3.121 (95%CI:1.288-7.651).The hyperlipidemia patients with MS 2756AG/GG genotype had a higher concentration of TC (5.87±0.89 mmol/L vs 5.46±0.93 mmol/L,P<0.05) and LDL-C (3.29±0.81 mmol/L vs 2.94±0.85 mmol/L,P<0.05)than those with AA genotype.However,individuals with 2756AG/GG genotype showed no significant difference in tHcy among those with AA genotype.Conclusion Hhcy and MS A2756G mutation may be the risk factors for combined hyperlipidemia.Further study is needed to confirm the role of Hhcy and MS A2756G mutation in the development of hyperlipidemia.

[1] Brattstrom,L;links.se;Wilcken,DE;Ohrvik,J;Brudin,L .Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis.[J].Circulation,1998(23):2520-2526.

[2] McCully K S .Homocysteine and vascular disease[J].Nature Medicine,1996,2(04):386-389.

[3] den Heijer M;Rosendaal F R;Blom H J et al.Hyperhomocysteinemia and venous thrombosis:a meta-analysis[J].Thrombosis and Haemostasis,1998,80(06):874-877.

[4] Ueland PM;Refsum H;Beresford SA;Vollset SE .The controversy over homocysteine and cardiovascular risk (see comments)[J].The American Journal of Clinical Nutrition: Official Journal of the American Society for Clinical Nutrition,2000(2):324-332.

[5] Boushey C J;Beresford S A;Omenn G S et al.A quantitative assessment of plasma homocysteine as a risk factor for vascular disease.Probable benefits of increasing folic acid intakes[J].Journal of the American Medical Association,1995,274(13):1049-1057.

[6] Aguilar B;Rojas J C;Collados M T .Metabolism of homocysteine and its relationship with cardiovascular disease[J].Journal of Thrombosis and Thrombolysis,2004,18(02):75-87.

[7] Klerk M;Verhoef P;Clarke R;Blom HJ;Kok FJ;Schouten EG .MTHFR 677C-->T Polymorphism and Risk of Coronary Heart Disease: A Meta-analysis.[J].JAMA: the Journal of the American Medical Association,2002(16):2023-2031.

[8] Leclerc D;Campeau E;Goyette P et al.Human methionine synthase:cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders[J].Human Molecular Genetics,1996,5(12):1867-1874.

[9] YING XIAO,ZHEN-TAO ZHANG,JUN-BO WANG,WEN-LI ZHU,YAO ZHAO,SHAO-FANG YAN,YONG LI.Effects of Dietary Intervention on Hyperlipidemia in Eight Communities of Beijing, China[J].生物医学与环境科学(英文版),2003(02):112-118.

[10] te Poele-Pothoff M T;van den Berq M;Franken D G et al.Three different methods for the determination of total homocysteine in plasma[J].Annals of Clinical Biochemistry,1995,32:218-220.

[11] Skibola C F;Smith M T;Kane E et al.Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults[J].Proceedings of the National Academy of Sciences(USA),1999,96(22):12810-12815.

[12] WEN-LI ZHU,JUN CHENG,JING-JING DAO,RU-BING ZHAO,LI-YING YAN,SHU-QING LI,YONG LI.Polymorphism of Methionine Synthase Gene in Nuclear Families of Congenital Heart Disease[J].生物医学与环境科学(英文版),2004(01):57-64.

[13] Nygard O;Vollset S E;Refsum H et al.Total plasma homocysteine and cardiovascular risk profile.The Hordaland Homocysteine Study[J].Journal of the American Medical Association,1995,274(19):1526-1533.

[14] Karmin O;Lynn E G;Chung Y H et al.Homocysteine stimulates the production and secretion of cholesterol in hepatic cells[J].Biochimica Et Biophysica Acta,1998,1393(2-3):317-324.

[15] Werstuck GH;Lentz SR;Dayal S;Hossain GS;Sood SK;Shi YY;Zhou J;Maeda N;Krisans SK;Malinow MR;Austin RC .Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways.[J].The Journal of Clinical Investigation: The Official Journal of the American Society for Clinical Investigation,2001(10):1263-1273.

[16] Liao D;Tan H;Hui R et al.Hyperhomocysteinemia decreases circulating high-density lipoprotein by inhibiting apoliprotein A-I Protein synthesis and enhancing HDL cholesterol clearance[J].Circulation Research,2006,99(06):598-606.

[17] 李勇,成君,朱文丽,刀京晶,闫丽盈,李孟忆,李书琴.先天性心脏病核心家庭血清同型半胱氨酸水平及相关基因多态性研究[J].北京大学学报(医学版),2005(01):75-80.

[18] Frosst P;Biota H J;Milos R et al.A candidate genetic risk factor for vascular disease:a common mutation in methylenetetrahydrofolate reductase[J].Nature Genetics,1995,10(01):111-113.

[19] Yilmaz H;Agachan B;Isbir T;Akoglu E .Is there additional effect of MTHFR C677T mutation on lipid abnormalities in renal allograft recipients?[J].Transplantation Proceedings,2003(4):1390-1392.

[20] Zuntar I;Antoljak N;Vrkic N et al.Association of methylenetetrahydrofolate(MTHFR)and apolipoprotein E(apo E)genotypes with homocysteine,vitamin and lipid levels in carotid stenosis[J].Coil Antropo,2006,30(04):871-878.

[21] Veerkamp M J;de Graaf J;den Heijer M et al.Plasma homocysteine in subjects with thmilial combined hyperlipidemia[J].Atheroclerosis,2003,166(01):111-117.

[22] Zhang G;Dai C .Gene polymorphisms of homocysteine metabolism-related enzymes in Chinese patients with occlusive coronary artery or cerebral vascular diseases.[J].Thrombosis Research: An International Journal on Vascular Obstruction, Hemorrhage and Hemostasis,2001(3):187-195.

[23] Laraqui A;Allami A;Carrie A;Coiffard AS;Benkouka F;Benjouad A;Bendriss A;Kadiri N;Bennouar N;Benomar A;Guedira A;Raisonnier A;Fellati S;Srairi JE;Benomar M .Influence of methionine synthase (A2756G) and methionine synthase reductase (A66G) polymorphisms on plasma homocysteine levels and relation to risk of coronary artery disease.[J].Acta Cardiologica,2006(1):51-61.

[24] Harmon D L;Shields D C;Woodside J V et al.Methionine synthase D919G polymorphism is a significant but modest determinant of circulating homocysteine concentrations[J].Genetic Epidemiology,1999,17(04):298-309.

[25] Jacques P F;Bostom A G;Selhub J et al.Effects of polymorphisms of methionine synthase and methionine synthase reductase on total plasma homocysteine in the NHLBI Family Heart Study[J].Atheroclerosis,2003,166(01):49-55.

[26] Hyndman M E;Bridge P J;Warnica J W et al.Effect of heterozygosity for the methionine synthase,2756 A>G mutationon the risk for recurrent cardiovascular events[J].American Journal of Cardiology,2000,86(10):1144-1146,A9.

[27] Morita H;Kurihara H;Sugiyama T et al.Polymorphism of the methionine synthase gene-association with homocysteine metabolism and late-onset vascular diseasesin the Japanese population[J].Arteriol Thromb Vase Biol,1999,19(02):298-302.

[28] Rafique S;Guardascione M;Osman E et al.Reversal of extrahepatic membrane cholesterol deposition in patients with chronic liver diseases by S-adenosyl-L-methionine[J].Clinical Science(London),1992,83(03):353-356.

[29] Chawla R K;Bonkovsky H L;Galambos J T .Biochemistry and pharmacology of S-adenosyl-L-methionine and rationale for its use in liver disease[J].Drugs,1990,40(z3):98-110.

[30] Klerk M;Lievers KJ;Kluijtmans LA;Blom HJ;den Heijer M;Schouten EG;Kok FJ;Verhoef P .The 2756A>G variant in the gene encoding methionine synthase: its relation with plasma homocysteine levels and risk of coronary heart disease in a Dutch case-control study.[J].Thrombosis Research: An International Journal on Vascular Obstruction, Hemorrhage and Hemostasis,2003(2/3):87-91.


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基金北京市自然科学基金(7072044)


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