DNA restriction fragment length polymorphisms as markers of familial coronary heart disease
W H Price1, S W Morris, A H Kitchin
1University Department of Medicine, Western General Hospital, Edinburgh.
Insights
Men with a family history of coronary heart disease (CHD) and specific gene variants are at significantly higher risk. These genetic factors, linked to apolipoprotein genes, explain a substantial portion of CHD prevalence.
Area of Science:
- Cardiovascular Genetics
- Molecular Epidemiology
Background:
- Family history is a known risk factor for coronary heart disease (CHD).
- Genetic predispositions, particularly involving apolipoprotein genes, may influence CHD risk.
- Restriction fragment length polymorphisms (RFLPs) can identify genetic variations associated with disease.
Purpose of the Study:
- To investigate the association between family history of CHD, specific RFLPs, and CHD prevalence in men.
- To determine the contribution of minor alleles of RFLPs near apo AI and apo CIII genes to CHD risk.
Main Methods:
- Case-control study analyzing 713 men aged 30-59.
- Genotyping for 4 RFLPs (XmnI, PstI, MspI, SacI) using restriction enzymes.
- Statistical analysis of CHD prevalence based on family history and RFLP genotypes.
Main Results:
- Men with a family history of CHD were twice as likely to have CHD.
- Minor alleles of RFLPs near apo AI/apo CIII genes significantly increased CHD prevalence by 234% in men with a family history.
- These RFLP associations accounted for approximately 20% of total CHD in the population.
Conclusions:
- Specific minor alleles of RFLPs in the apo AI/apo CIII region are strongly associated with increased CHD risk, particularly in men with a family history.
- These genetic variants play a significant role in the development of coronary heart disease.
- The findings highlight the importance of genetic screening for CHD risk assessment.
Abstract:
246 of 713 men aged 30 to 59 years had first-degree relatives who had had coronary heart disease (CHD) by the age of 60; men with a family history of CHD were twice as likely to have CHD themselves, compared with those without such a family history. At least 75% of the difference was accounted for by CHD in men with minor alleles of 4 restriction fragment length polymorphisms (RFLPs) in the region of the apolipoprotein (apo) AI and apo CIII genes. The RFLPs were identified with the restriction enzymes XmnI, PstI, MspI, and SacI. Each polymorphism has two alleles (major and minor), designated X1 and X2, P1 and P2, M1 and M2, and S1 and S2, respectively. In men with any one of the minor alleles, a family history of CHD was associated with a 234% increase in CHD prevalence. In men with major alleles only, a family history of CHD was not associated with any significant increase in CHD. The effect of the minor alleles was not significantly altered when plasma lipids and other variables except for age were taken into account. The association between the minor RFLP alleles and polymorphic gene variants (probably the apo AI, apo CIII, or both genes) which enhance liability to CHD accounted for almost 20% of total CHD in this population.
More Related Videos
Related Concept Videos
Single Nucleotide Polymorphisms-SNPs
Restriction Enzymes
The host bacteria protect their own genomic DNA from these enzymes by methylating these sites. Some...
Pharmacogenomics: Identification of New Drug Targets


