Familial resemblance of plasma apolipoprotein B: the Nancy study

The familial resemblance of plasma apolipoprotein B (apo B) was investigated in a sample of 102 families including 419 members who volunteered for a free health checkup in the Preventive Center of Vandoeuvre-lès-Nancy, France. The mean levels (+/- SD) of apo B were 141.0 (+/- 32.6), 121.8 (+/- 27.7), and 98.6 (+/- 22.6) mg/dl in fathers, mothers, and offspring, respectively. The familial correlations were 0.04, 0.13, 0.21 (P less than .01), and 0.47 (P less than .001) between spouses, father-offspring, mother-offspring, and siblings, respectively, after adjustment on age, body mass index, and sex. A genetic analysis was performed using the approach proposed by Bonney, which indicated that a recessive and a dominant major-locus model appeared nearly equally supported by the data. Under the recessive model, the frequency q of the most common allele was estimated as 0.825, with a mean difference of 60.4 mg/dl between high and low homozygotes. Under the dominant model, q was estimated as 0.875, with a mean increase of 34.2 mg/dl in heterozygotes and high homozygotes. However, the hypothesis of Mendelian transmission and the environmental hypothesis could not be formally tested because of great numeric difficulties encountered in the estimation of the three transmission probabilities. Given these analytical restrictions, we cannot conclude in favor of a major locus influencing apo B level in our population, even though the evidence is suggestive. The genetic heterogeneity underlying the familial aggregation of apo B level, suggested by several recent publications, might explain the difficulty in discerning a single major locus in a population sample of small nuclear families, not ascertained through patients enriching the sample in high values of apo B. These findings call into question the relevance of the approach through "healthy" populations in the search for major loci influencing biological traits.