Genetic contributions to LDL-C, Apo-B and LDL-C/Apo-B ratio in a sample of Israeli offspring with a parental history of myocardial infarction.

Abstract

One hundred and forty sibships consisting of 280 brothers and 256 sisters with a family history of myocardial infarction were investigated for the possible involvement of a major gene in the determination of LDL-C, Apo-B and LDL-C/ Apo-B ratio (as a surrogate for LDL subclasses). The mean ages were 29.5 years (range 15-48) and 29.2 years (range 15-47), for brothers and sisters, respectively, and values were initially adjusted for age effects through multiple regression analysis. Results from commingling analysis indicated that for LDL-C a single normal distribution fitted the data as well as a mixture of two distributions. For Apo-B, a mixture of two normal distributions fitted the data significantly better than a single distribution (chi 2 = 7.8, df = 2, p = 0.02). For LDL-C/ Apo-B ratio a mixture of three normal distributions fitted the data significantly better than two distributions (chi 2 = 9.2, df = 2, p = 0.01). A regression analysis applied to the logarithm of the sex- and age-adjusted mean and variance within sibship, showed no indication of a major gene involvement for LDL-C. For Apo-B and LDL-C/Apo-B ratio, there existed, however, significant linear relationships between the logarithmically transformed means and within sibship variances which support the involvement of major genes. In addition, the Bartlett test applied to the data of within-sibship variances also rejected the null hypothesis of multifactorial transmission for Apo-B and LDL-C/Apo-B ratio (p < 0.0001). Lastly, the results from sib-pair linkage analyses provided significantly positive evidence for linkage between ApoB levels and the Apo-B XbaI restriction site.