RFLP Markers of Familial Coronary Heart Disease

  • William H. Price
  • Arthur H. Kitchin
Part of the NATO ASI Series book series (NSSA, volume 214)

Abstract

In two population samples of men aged 30–59 years from the North of Edinburgh, a higher frequency of CHD in those with a family history of the disease in close relatives before age 60 was strongly associated with the allele status of four RFLP in the apo AI/CIII/AIV gene region. In a simultaneous multiple logistic regression analysis of CHD on a number of covariates, a family history emerged with significant odds ratio of 2.553 (p = 0.034) in subjects with minor RFLP alleles in one of the samples and with odds ratio of 3.611 (p = 0.016) in those homozygous for major alleles in the other. The apo AI/CIII/AIV related effect of family history on evidence of CHD was independent of all other variables tested, which included age, cigarette smoking, hypertension, hyperlipldaemia, socio-economic group and obesity. There was no evidence of a familial environment effect or of genotype environment interaction. The results of these studies suggest that genetic liability to CHD is influenced significantly by a locus or loci in the apo AI/CIII/AIV gene region. Since the association of this region with familial CHD involves different alleles or haplotypes in different sections of the population (different linkage phase) no single allele or haplotype identifies an individual with increased liability to CHD on account of this association. This may explain the apparently conflictng results obtained in case control studies.

Keywords

Cholesterol Obesity Glycerol Covariance Heparin 

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References

  1. 1.
    Neufeld HN, Goldbourt U. Coronary Heart Disease: Genetic Aspects. Circulation 1983; 67: 943–54.PubMedCrossRefGoogle Scholar
  2. 2.
    Goldbourt U, Neufeld HN. Genetic Aspects of Arteriosclerosis. Arteriosclerosis 1986; 6: 357–77.PubMedCrossRefGoogle Scholar
  3. 3.
    Hopkins PN, Williams RR. Human Genetics and Coronary Heart Disease: A Public Health Perspective. Annu Rev Nutr 1989; 9: 303–45.PubMedCrossRefGoogle Scholar
  4. 4.
    Karathanasis SK, Norum RA, Zannis VI, Breslow JL. An Inherited Polymorphism in the Human ApolipoproteinAI Gene Locus related to the Development of Atherosclerosis. Nature 1983; 301: 718–20.PubMedCrossRefGoogle Scholar
  5. 5.
    Rees A, Shoulders CC, Stokes J, Galton DJ, Baralle FE. DNA Polymorphism adjacent to Human Apo-Protein A-I Gene. Relation to Hypertriglyceridaemia. Lancet 1983; i: 444–6.CrossRefGoogle Scholar
  6. 6.
    Ferns GAA, Galton DJ. Haplotypes of Human Apolipoprotein AI-CIII-AIV Gene Cluster in CoronaryAtherosclerosis. Hum Genet 1986: 73: 245–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Breslow JL. Apolipoprotein Genetic Variation and Human Disease. Physiol Rev 1988; 68: 85–132.PubMedGoogle Scholar
  8. 8.
    Fisher EA, Coates PM and Cortner JA. Gene Polymorphisms and Variability of Human Apolipoproteins. Annu Rev Nutr 1989; 9: 139–60.PubMedCrossRefGoogle Scholar
  9. 9.
    Sing FC, Moll PP. Genetics of variability of CHD risk. Int J Epidemiol 1989; 18: 5183–95Google Scholar
  10. 10.
    Price WH, Morris SW, Kitchin AH, Wenham PR, Burgon PRS and Donald PM. DNA restriction fragment length polymorphisms as markers of familial coronary heart disease. Lancet 1989; i: 1407–1410CrossRefGoogle Scholar
  11. 11.
    Price WH, Morris SW. Kitchin AH, Wenham PR, Lowther JL, M’Kenzie PRS and Donald PM.Further evidence implicating the apo AI/CIII/ AN gene region in genetic liability to CHD. In preparation.Google Scholar
  12. 12.
    Kunkel LM, Smith KD, Boyer SH, et al. Analysis of Y Chromosome Specific Reiterated DNA inChromosome Variants. Proc Natl Acad Sci USA 1977; 74: 1245–49.PubMedCrossRefGoogle Scholar
  13. 13.
    Lee J. Covariance adjustment of rates based on the multiple logistic regression model. J Chron Dis1981; 34: 415–426PubMedCrossRefGoogle Scholar
  14. 14.
    Falconer DS. The inheritance of liability to certain diseases, estimated from the incidence among relatives. Ann Hum Gen 1965; 29 51–62CrossRefGoogle Scholar
  15. 15.
    Shaper AG, Pocock SJ. Walker M, Phillips AN, Whitehead TP, Macfarlane PW. Risk factors for ischaemic heart disease: the prospective phase of the British regional heart study. J Epid CommHealth 1985; 39: 197–209CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • William H. Price
    • 1
  • Arthur H. Kitchin
    • 1
  1. 1.University Department of Medicine and M.R.C. Human Genetics UnitWestern General HospitalEdinburghUK

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