Advertisement

Polymorphism of the apolipoprotein B gene and blood lipid concentrations in Japanese and Caucasian population samples

      Abstract

      To examine whether a racial difference in apolipoprotein B (Apo B) gene polymorphism between Japanese and American Caucasians corresponds with the lower blood cholesterol concentrations in Japanese than in Americans, we examined the EcoRI polymorphism of the Apo B gene for 271 nonsmoking men and women aged 47–69 years in two population-based samples: rural Japanese living in Akita and Caucasians living in Minneapolis-St. Paul, Minnesota, USA. Mean values of serum cholesterol concentrations were significantly lower in Japanese than in Caucasians for both men and women (difference = 25–26 mg/dl). An allele-specific polymerase chain reaction was conducted to examine the EcoRI cutting site at the 12 669 cDNA position of the Apo B gene. The allele R2 (absence of the cutting site) has been associated with lower cholesterol concentrations in two previous studies. The frequency of the R2 allele was 6% for Japanese and 17% for Caucasians (P < 0.001), and this race difference in allele frequency was identical for men and women. After controlling for age, body mass index, alcohol intake, and, for women, menopausal status and hormone replacement therapy, the adjusted mean (SE) cholesterol level among Japanese was 204 (3) mg/dl for genotype R1R1 and 185 (7) mg/dl for genotype R1R2 or R2R2 combined (P = 0.01). The respective mean values among Caucasians were 224(5) mg/dl and 232(7) mg/dl (P = 0.36). The polymorphism had a similar effect on total cholesterol concentrations for both men and women. The observed lower prevalence of the R2 allele in Japanese than in Caucasians indicates that this variation in the Apo B gene does not explain the racial difference in blood cholesterol concentrations.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Keys A.
        Summary: coronary heart disease in seven countries.
        Circulation. 1970; 42: 186-198
        • Keys A.
        The diet: coronary heart disease in seven countries.
        Circulation. 1970; 42: 162-183
      1. International Collaborative Study Group. Metabolic epidemiology of plasma cholesterol within populations and between populations. Lancet 1986;2:991–995.

        • Kagan A
        • Harris BR
        • Winkelstein Jr, W
        • et al.
        Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii, and California: demographic, physical, dietary and biochemical characteristics.
        J Chron Dis. 1974; 27: 345-364
        • Blakhart BD
        • Ludwig EM
        • Pierotti VR
        • et al.
        Structure of the human apolipoprotein B gene.
        J Biol Chem. 1986; 261: 15364-15367
        • Soria LF
        • Ludwig EH
        • Clarke HRG
        • Vega GL
        • Grundy SM
        • McCarthy BJ
        Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100.
        Proc Natl Acad Sci USA. 1989; 86: 587-591
        • Bersot TP
        • Russell SJ
        • Thatcher SR
        • et al.
        A unique hapolotype of the apolipoprotein B-100 allele associated with familial defective apolipoprotein B-100 in a Chinese man discovered during a study of the prevalence of this disorder.
        J Lipid Res. 1993; 34: 1149-1154
        • Berg K
        DNA polymorphism at the apolipoprotein B locus is associated with lipoprotein level.
        Clin Genet. 1986; 30: 515-520
        • Law A
        • Powell LM
        • Brunt H
        • et al.
        Common DNA polymorphism within coding sequence of apolipoprotein B gene associated with altered lipid levels.
        Lancet. 1986; 1: 1301-1303
        • Talmud PJ
        • Barni N
        • Kessling AM
        • et al.
        Apoliprotein B gene variants are involved in the determination of serum cholesterol levels: a study in normo- and hyperlipidaemic individuals.
        Atherosclerosis. 1987; 67: 81-89
        • Peacook R
        • Dunning A
        • Hamsten A
        • Tornvall P
        • Humphries S
        • Talmud P
        Apolipoprotein B gene polymorphisms, lipoproteins and coronary atherosclerosis: a study of young mycardinal infarction survivors and healthy population-based individuals.
        Atherosclerosis. 1992; 92: 151-164
        • Bohn M
        • Bakken A
        • Erikssen J
        • Berg K
        XbaI polymorphism in DNA at the apolipoprotein B locus is associated with myocardial infarction (MI).
        Clin Genet. 1993; 44: 241-248
        • Hansen PS
        • Klausen IC
        • Lemming L
        • Gerdes LU
        • Gregersen N
        • Faergeman O
        Apolipoprotein B gene polymorphisms in ischemic heart disease and hypercholesterolemia: effects of age and sex.
        Clin Genet. 1994; 45: 78-83
        • Hegele RA
        • Huang LS
        • Herbert PN
        • et al.
        Apolipoprotein B-gene DNA polymorphisms associated with myocardial information.
        New Engl J Med. 1986; 315: 1509-1515
        • Myant NB
        • Gallagher J
        • Barbir M
        • Thompson GR
        • Wile D
        • Humphries SE
        Restriction fragment length polymorphisms in the Apo B gene in relation to coronary artery disease.
        Atherosclerosis. 1989; 77: 193-201
        • Darnfors C
        • Wiklund O
        • Nilsson J
        • et al.
        Lack of correlation between the apolipoprotein B XbaI polymorphism and blood lipid levels in a Swedish population.
        Atherosclerosis. 1989; 75: 183-188
        • Carlsson P
        • Darnfors C
        • Olofsson S-O
        • Bjunsell G
        Analysis of the human apolipoprotein B gene: complete structure of the B-74 region.
        Gene. 1986; 49: 29-34
        • Demant T
        • Houlston RS
        • Caslake MJ
        • et al.
        Catabolic rate of low density lipoprotein is influenced by variation in the apolipoprotein gene.
        J Clin Invest. 1988; 82: 797-802
        • Houlston RS
        • Turner PR
        • Lewis B
        • Humphries SE
        Genetic epidemiology of differences in low-density lipoprotein (LDL) cholesterol concentration: possible involvement of variation at the apolipoprotein B gene locus in LDL kinetics.
        Genet Epidemiol. 1990; 7: 199-210
        • Tybjaerg-Hansen A
        • Nordestgaard BG
        • Gerdes LU
        • Humphries SE
        Variation of apolipoprotein B gene is associated with myocardial infarction and lipoprotein levels in Dane.
        Atherosclerosis. 1991; 89: 69-81
        • Deeb S
        • Failor A
        • Brown BG
        • Brunzell JD
        • Albers JJ
        • Motulsky AG
        Molecular genetics of apolipoproteins and coronary heart disease.
        Cold Spring Harbor Symp Quant Biol. 1986; 51: 403-409
        • Paulweber R
        • Friedl W
        • Krempler F
        • Humphries SE
        • Sandhofer F
        Association of DNA polymorphism at the Apolipoprotein B gene locus with coronary heart disease and serum very low density lipoprotein levels.
        Arteriosclerosis. 1990; 10: 17-24
        • Genest Jr, JJ
        • Ordovas JM
        • McNamara JR
        • et al.
        DNA polymorphisms of the apolipoprotein B gene in patients with premature coronary artery disease.
        Atherosclerosis. 1990; 82: 7-17
        • Saha N
        • Tong MC
        • Tay JSH
        • Jeyaseelan K
        • Humphries SE
        DNA polymorphisms of the apolipoprotein B gene in Chinese coronary heart disease patients.
        Clin Genet. 1992; 42: 164-170
        • Aburatani H
        • Murase T
        • Takaku F
        • Itoh H
        • Matsumoto A
        • Itakura H
        Apolipoprotein B-gene polymorphism and myocardial infarction.
        New Engl J Med. 1987; 317: 52
        • Aburatani H
        • Matsumoto A
        • Itoh H
        • et al.
        A study of DNA polymorphism in the apolipoprotein B gene in a Japanese population.
        Atherosclerosis. 1988; 72: 71-76
        • Knott TJ
        • Rall Jr, SC
        • Innerarity TL
        • et al.
        Human apoliopoprotein B: structure of carboxyl-terminal domains, sites of gene expression, and chromosomal localization.
        Science. 1985; 230: 37-43
        • Humphries SE
        DNA polymorphisms of the apolipoprotein genes—their use in the investigation of the genetic component of hyperlipidemia and atherosclerosis.
        Atherosclerosis. 1988; 72: 89-108
        • Rajput-Williams J
        • Knott TJ
        • Wallis SC
        • et al.
        Variation of apolipoprotein-B gene is associated with obesity, high blood cholesterol levels, and increased risk of coronary heart disease.
        Lancet. 1988; 2: 1442-1446
        • De Benedictis G
        • Rose G
        • Mazzei R
        • et al.
        EcoRI-RFLP of the Apo B gene: a study in a sample group from South Italy.
        Ann Hum Genet. 1991; 55: 103-113
      2. The ARIC Investigators. The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. Am J Epidemiol 1989:129;687–702.

        • Shimamoto T
        • Komachi Y
        • Inada H
        • et al.
        Trends for coronary heart disease and stroke and their risk factors in Japan.
        Circulation. 1989; 79: 503-515
        • Iso H
        • Folsom AR
        • Sato S
        • et al.
        Plasma fibrinogen and its correlates in US and Japanese population samples.
        Arterios Thromb. 1993; 13: 783-790
      3. Meade TW, Imerson J, Stirling Y. Effects of changes in smoking and other characteristics on clotting factors and the risk of ischemic heart disease. Lancet 1987;ii:986–88.

        • Goldbourt U
        • Medalie JH
        Characteristics of smokers, non-smokers and ex-smokers among 10,000 adult males in Israel.
        Am J Epidemiol. 1977; 105: 75-86
      4. National Heart, Lung and Blood Institute. ARIC Manuals of Operations: 7. Blood Collection and Processing; 8. Lipid and Lipoprotein Determination; 9. Hemostasis Determinations. Chapel Hill, NC: ARIC Coordinating Center, School of Public Health, University of North Carolina.

        • Nagele U
        • Hagele EO
        • Sauer G
        • et al.
        Reagent for the enzymatic determination of serum total triglycerides with improved lipolytic efficiency.
        J Clin Chem Biochem. 1984; 22: 165-174
      5. Manual of Laboratory Operations, Lipid Research Clinics Program: lipid and lipoprotein analysis. Bethesda, MD, US: Department of Health and Welfare Publication 1974;1:75–628.

        • Nakamura M
        • Morita M
        • Yabuuchi E
        • et al.
        The evaluation and the results of cooperative cholesterol and triglyceride standardization program by WHO-CDC.
        Rinsho Byori. 1982; 30 (in Japanese): 325-332
        • Warnick GR
        • Benderson JM
        • Albers JJ
        Quantization of high-density-lipoprotein subclasses after separation by dextran sulfate and Mg2+ precipitation.
        Clin Chem. 1982; 28 (Abstract): 1574
        • Friedewald WT
        • Levy RI
        • Fredrickson DS
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
        Clin Chem. 1972; 18: 499-502
      6. Cloey T, Bachorik PS, Becker D, Finney C, Lowry D, Sigmund W. Reevaluation of serum-plasma differences in total cholesterol concentrations. JAMA 1990;263:2788–89.

        • Owan I
        • Suda T
        Strategy of osteoporosis therapy (in Japanese).
        J Clin Exp Med (Igaku no Ayumi). 1992; 160: 115-117
      7. The Ministry of Health and Welfare. A report of National Survey on Circulatory Disorders 1990. Tokyo: Cardiovascular Disease Research Foundation 1993 (in Japanese, English abstract).

        • Johnson CL
        • Rifkind BM
        • Sempos CT
        • et al.
        Declining serum total cholesterol levels among US adults. The National Health and Nutrition Examination Surveys.
        JAMA. 1993; 269: 3002-3008
        • Renges HH
        • Wile DB
        • McKeigue PM
        • Marmot MG
        • Humphries SE
        Apolipoprotein B gene polymorphisms are associated with lipid levels in men of South Asian decent.
        Atherosclerosis. 1991; 91: 267-275
        • Saha N
        • Tay JSH
        • Heng CK
        • Humphries SE
        DNA polymorphisms of the apolipoprotein B gene are associated with obesity and serum lipids in healthy Indians in Singapore.
        Clin Genet. 1993; 44: 113-120
        • Saha N
        • Tay JSH
        • Humphries SE
        Apolipoprotein B-gene DNA polymorphisms (XbaI and EcoRI), serum lipids, and apolipoproteins in healthy Chinese.
        Genet Epidemiol. 1992; 9: 1-10
        • Beaumont JL
        • Carlson LA
        • Cooper GB
        • Fejfar Z
        • Frederickson DS
        • Strasser J
        Classification of hyperlipidemia and hyperlipoproteinaemias.
        Bull WHO. 1970; 43: 891-915