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Restriction fragment length polymorphisms at the apoprotein genes AI, CIII and B‐100 and in the 5‘ flanking region of the insulin gene as possible markers of coronary heart disease
Author(s) -
Wick Ursula,
Witt Erwin,
Engel Wolfgang
Publication year - 1995
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.1995.tb03957.x
Subject(s) - genetics , gene , restriction fragment length polymorphism , biology , 5' flanking region , coronary heart disease , restriction fragment , medicine , polymerase chain reaction , promoter , gene expression
Several sequence variations were examined for being endogenous “risk markers” in the development of CHD. The “markers” in this study included: the PstI‐SstI RFLPs in the apo AI‐CIII gene cluster, the EcoRI‐MspI RFLPs in the apo B100 gene and the SstI RFLP in the 5‘ flanking region of the insulin gene. The study population comprised 700 individuals of German origin. A strong association of these “markers” to the disease phenotype predicts their loss in healthy individuals with ages above that of the prevalent incidence of CHD. In contrast, these “markers” should accumulate in diseased persons. A significant age‐dependent selection was observed for the EcoRI RFLP in the apo B100 gene. This was the case when the allele and genotype frequencies of healthy old individuals were compared with those of newborns. In contrast, no RFLP showed significant differences in allele and genotype distributions between patients defined by coronary angiography and controls. In the group of patients, but not controls, several RFLP genotypes were found to be associated with significantly higher serum levels of cholesterol and triglycerides. This was true in the case of serum cholesterol comparing the genotypes S 1 S 2 with those of S 1 S 1 ( p =0.05) observed for the SstI polymorphic site in the 3’ noncoding region of the apo CIII gene. Significantly higher levels of triglycerides were found within the heterozygous patients P 1 P 2 ( p =0.045) and S 1 S 2 ( p =0.02) than in the homozygotes P 1 P 1 and S 1 S 1 for the PstI‐SstI RFLPs at the apo AI‐CIII gene cluster. The SstI RFLP in the 5‘ flanking region of the insulin gene also revealed significantly higher values of triglycerides among the patients with the genotype UU compared to the heterozygotes LU ( p =0.005) and to the homozygotes LL ( p =0.0008). Among the patients, the combined genotype P 1 P 2 S 1 S 2 for the PstI‐SstI RFLPs at the apo AI‐CIII genes first had higher serum cholesterol levels than the genotype P 1 P 2 S 1 S 1 ( p =0.02) and secondly had higher values of serum triglycerides compared to the genotypes: P 1 P 1 S 1 S 1 ( p =0.01), P 1 P 2 S 1 S 1 ( p =0.02) and P 1 P 1 S 1 S 2 ( p =0.03).