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/

One hundred and forty sibships consisting of 280 brothers and 256 sist ers with a family history of myocardial infarction were investigated f or the possible involvement of a major gene in the determination of LD L-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 15-4 7), 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 di stribution fitted the data as well as a mixture of two distributions. For Apo-B, a mixture of two normal distributions fitted the data signi ficantly 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 indicatio n of a major gene involvement for LDL-C. For Apo-B and LDL-C/Apo-B rat io, there existed, however, significant linear relationships between t he logarithmically transformed means and within sibship variances whic h support the involvement of major genes. In addition, the Bartlett te st applied to the data of within-sibship variances also rejected the n ull 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 lev els and the ApoB XbaI restriction site.