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To determine the frequency of familial hypoalphalipoproteinemia in the general population due to mutation of the apolipoprotein A-I (apo A-I) gene, we analyzed sequence variations in the apo A-I gene. The subjects were 67 children with a low high-density lipoprotein (HDL) cholesterol level (≤38 mg/dl, below the fifth per-centile in the population of this study) who were screened from 1254 schoolchildren through a school survey. Four different mutations with deleterious potential, three frameshifts and one splice site mutation, were identified in four of the subjects. The plasma apo A-I levels of the four children with apo A-I gene mutations were reduced to approximately half of the normal levels and were below the first percentile of the general population distribution (80 mg/dl). Thus, the frequency of hypoalphalipoproteinemia due to a mutant apolipo-protein A-I gene was estimated at 6% (95% CI: 2.4–14.4%) in the subjects with low HDL cholesterol levels and 0.3% (95% CI: 0.1–0.8%) in the Japanese population. This suggests that familial hypoalphalipo-proteinemia due to apo A-I gene mutations is relatively common.

Frequent Occurrence of Hypoalphalipoproteinemia Due to Mutant Apolipoprotein A-I Gene in the Population: A Population-Based Survey