Common polymorphism in promoter of microsomal triglyceride transfer protein gene influences cholesterol, ApoB, and triglyceride levels in young african american men: results from the coronary artery risk development in young adults (CARDIA) study.

The microsomal triglyceride transfer protein (MTP) plays a key role in the assembly of apolipoprotein B (apoB)-containing lipoproteins. We investigated the relation between lipid profiles and a common functional polymorphism (-493G/T) of the MTP gene in a large sample of young black men in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. We performed serial cross-sectional analyses on lipids of 586 black men in 5 exams over 10 years of follow-up. Total cholesterol, LDL cholesterol, and apoB levels were very similar between the GT and GG genotypes; therefore, the GT and GG genotypes were combined as 1 group when the 3 phenotypes were analyzed. The results from ANCOVA showed that the TT group (prevalence 7%) had higher levels of apoB-related lipids than did the GT+GG group: the difference in total cholesterol ranged from 2 (P=0.79) to 19 (P=0.002) mg/dL in exams 1 to 5; the difference in LDL cholesterol ranged from 10 (P=0.14) to 17 (P=0.003) mg/dL in exams 1 to 4, but in examination 5, the difference became negligible. The TT group had higher levels of apoB, measured in only 2 exams, by 6 (P=0.12) and 9 (P=0.03) mg/dL. The TT group had higher levels of triglycerides than did the TG or GG group by 3 to 34 (P=0.02 to approximately 0.003) mg/dL in all 5 exams. HDL cholesterol and apolipoprotein A-I levels were similar among the 3 genotypes. Our serial cross-sectional analyses indicated that the TT genotype was associated with higher levels of total cholesterol, LDL cholesterol, triglycerides, and apoB in young black men. The broad effect of this polymorphism on several atherogenic traits suggests that the MTP gene could be influential in atherosclerosis.

[1]  D. Comings,et al.  Association of the serotonin transporter gene with serum cholesterol levels and heart disease. , 1999, Molecular genetics and metabolism.

[2]  D. Comings,et al.  Molecular heterosis as the explanation for the controversy about the effect of the DRD2 gene on dopamine D2 receptor density , 1999, Molecular Psychiatry.

[3]  L. Almasy,et al.  A genome search identifies major quantitative trait loci on human chromosomes 3 and 4 that influence cholesterol concentrations in small LDL particles. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[4]  D. Arveiler,et al.  Identification of two polymorphisms in the promoter of the microsomal triglyceride transfer protein (MTP) gene: lack of association with lipoprotein profiles. , 1998, Journal of lipid research.

[5]  H. Jamil,et al.  An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits. , 1998, Science.

[6]  AndersHamsten,et al.  A Common Functional Polymorphism in the Promoter Region of the Microsomal Triglyceride Transfer Protein Gene Influences Plasma LDL Levels , 1998 .

[7]  R. Krauss,et al.  Candidate-gene studies of the atherogenic lipoprotein phenotype: a sib-pair linkage analysis of DZ women twins. , 1998, American journal of human genetics.

[8]  D. Gordon.  Recent advances in elucidating the role of the microsomal triglyceride transfer protein in apolipoprotein B lipoprotein assembly. , 1997, Current opinion in lipidology.

[9]  B Müller-Myhsok,et al.  Genetic analysis of complex diseases. , 1997, Science.

[10]  E. Nicodème,et al.  Microsomal triacylglycerol transfer protein prevents presecretory degradation of apolipoprotein B-100. A dithiothreitol-sensitive protease is involved. , 1996, European journal of biochemistry.

[11]  B. Howard,et al.  Apolipoprotein E polymorphism in American Indians and its relation to plasma lipoproteins and diabetes. The Strong Heart Study. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[12]  J. Moberly,et al.  Inhibition of apolipoprotein B and triglyceride secretion in human hepatoma cells (HepG2). , 1996, Journal of lipid research.

[13]  L. Pérusse,et al.  Apolipoprotein E polymorphism in a French Canadian population of northeastern Quebec: allele frequencies and effects on blood lipid and lipoprotein levels. , 1996, Human biology.

[14]  Li-Shin Huang,et al.  Demonstration of a Physical Interaction between Microsomal Triglyceride Transfer Protein and Apolipoprotein B during the Assembly of ApoB-containing Lipoproteins (*) , 1996, The Journal of Biological Chemistry.

[15]  J. Hokanson,et al.  Plasma Triglyceride Level is a Risk Factor for Cardiovascular Disease Independent of High-Density Lipoprotein Cholesterol Level: A Metaanalysis of Population-Based Prospective Studies , 1996, Journal of cardiovascular risk.

[16]  M. Muros,et al.  Apolipoprotein E polymorphism influence on lipids, apolipoproteins and Lp(a) in a Spanish population underexpressing apo E4. , 1996, Atherosclerosis.

[17]  D. Jacobs,et al.  Change and secular trends in physical activity patterns in young adults: a seven-year longitudinal follow-up in the Coronary Artery Risk Development in Young Adults Study (CARDIA). , 1996, American journal of epidemiology.

[18]  M. Fox,et al.  Mutations of the microsomal triglyceride-transfer-protein gene in abetalipoproteinemia. , 1995, American journal of human genetics.

[19]  J. Breslow,et al.  Genetic basis of lipoprotein disorders. , 1989, Circulation.

[20]  D. Rader,et al.  Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. , 1992, Science.

[21]  J. Coresh,et al.  Comparison of the plasma levels of apolipoproteins B and A-1, and other risk factors in men and women with premature coronary artery disease. , 1992, The American journal of cardiology.

[22]  H. Brewer,et al.  Apolipoprotein C‐ll deficiency syndrome due to apo C‐IIHamburg: clinical and biochemical features and Hphl restriction enzyme polymorphism , 1992, European journal of clinical investigation.

[23]  D. Jacobs,et al.  Meat consumption and its associations with other diet and health factors in young adults: the CARDIA study. , 1991, The American journal of clinical nutrition.

[24]  R. Schieken.  Effect of Exercise on Lipids a , 1991, Annals of the New York Academy of Sciences.

[25]  H. Ginsberg,et al.  Oleate stimulates secretion of apolipoprotein B-containing lipoproteins from Hep G2 cells by inhibiting early intracellular degradation of apolipoprotein B. , 1991, The Journal of biological chemistry.

[26]  J. Borén,et al.  The assembly and secretion of apoB 100 containing lipoproteins in Hep G2 cells. Evidence for different sites for protein synthesis and lipoprotein assembly. , 1990, The Journal of biological chemistry.

[27]  K. Howell,et al.  Apolipoprotein B is both integrated into and translocated across the endoplasmic reticulum membrane. Evidence for two functionally distinct pools. , 1990, The Journal of biological chemistry.

[28]  J. Breslow,et al.  Genetic basis of lipoprotein disorders. , 1995, The Journal of clinical investigation.

[29]  A. Dyer,et al.  Ethnic differences in blood pressure, pulse rate, and related characteristics in young adults. The CARDIA study. , 1989, Hypertension.

[30]  J. Scott,et al.  The apolipoprotein B gene is constitutively expressed in HepG2 cells: regulation of secretion by oleic acid, albumin, and insulin, and measurement of the mRNA half-life. , 1989, Journal of lipid research.

[31]  J. Haddow,et al.  Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data. , 1989, BMJ.

[32]  M. Austin.  Plasma triglyceride as a risk factor for coronary heart disease. The epidemiologic evidence and beyond. , 1989, American journal of epidemiology.

[33]  Charles R.scriver,et al.  The Metabolic basis of inherited disease , 1989 .

[34]  D. Jacobs,et al.  Relationships of low density lipoprotein cholesterol with age and other factors: a cross-sectional analysis of the CARDIA study. , 1988, Annals of clinical research.

[35]  K. Namboodiri,et al.  Biological and cultural sources of familial resemblance in plasma lipids: A comparison between North America and Israel—the lipid research clinics program , 1988, Genetic epidemiology.

[36]  S B Hulley,et al.  CARDIA: study design, recruitment, and some characteristics of the examined subjects. , 1988, Journal of clinical epidemiology.

[37]  J. Albers,et al.  Comparison of commercial kits for apoprotein A-I and apoprotein B with standardized apoprotein A-I and B radioimmunoassays performed at the Northwest Lipid Research Center. , 1988, Journal of lipid research.

[38]  S B Hulley,et al.  Risk factors for coronary heart disease in adult female twins. Genetic heritability and shared environmental influences. , 1987, American journal of epidemiology.

[39]  L. Hunt,et al.  Serum apolipoproteins AI and B and lipoproteins in middle aged men with and without previous myocardial infarction. , 1986, British heart journal.

[40]  S. Zeger,et al.  Longitudinal data analysis using generalized linear models , 1986 .

[41]  K Y Liang,et al.  Longitudinal data analysis for discrete and continuous outcomes. , 1986, Biometrics.

[42]  Warnick Gr.  Enzymatic methods for quantification of lipoprotein lipids. , 1986 .

[43]  G. Warnick.  Enzymatic methods for quantification of lipoprotein lipids. , 1986, Methods in enzymology.

[44]  P. Bachorik,et al.  Precipitation methods for quantification of lipoproteins. , 1986, Methods in enzymology.

[45]  J. Albers,et al.  Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol. , 1982, Clinical chemistry.

[46]  W. Raynor,et al.  Diet, serum cholesterol, and death from coronary heart disease. The Western Electric study. , 1981, The New England journal of medicine.

[47]  R. Bawol,et al.  Epidemiology as a guide to clinical decisions. The association between triglyceride and coronary heart disease. , 1980, The New England journal of medicine.

[48]  D. Jacobs,et al.  Scoring systems for evaluating dietary pattern effect on serum cholesterol. , 1979, Preventive medicine.

[49]  M. Brown,et al.  The LDL receptor locus and the genetics of familial hypercholesterolemia. , 1979, Annual review of genetics.

[50]  Relationship of blood pressure, serum cholesterol, smoking habit, relative weight and ECG abnormalities to incidence of major coronary events: final report of the pooling project. The pooling project research group. , 1978, Journal of chronic diseases.

[51]  J. Goldstein,et al.  Heterozygous familial hypercholesterolemia: Failure of normal allele to compensate for mutant allele at a regulated genetic locus , 1976, Cell.

[52]  W. Hazzard,et al.  Immunoassay of human plasma apolipoprotein B. , 1975, Metabolism: clinical and experimental.

[53]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[54]  A. Keys,et al.  Serum cholesterol response to changes in dietary lipids. , 1966, The American journal of clinical nutrition.

[55]  F. Grande,et al.  Serum cholesterol response to changes in the diet: I. Iodine value of dietary fat versus 2S-P. , 1965, Metabolism: clinical and experimental.

[56]  A. Keys,et al.  Serum cholesterol response to changes in the diet: II. The effect of cholesterol in the diet. , 1965, Metabolism: clinical and experimental.