科学家报告了一个在普通人群中寻找与“好”胆固醇低有关的基因变异的新方法。这个方法也能用于寻找与其他疾病有关的基因变异，有些变异靠研究有遗传病史的小家族是很难找到的。科学家说，“好”胆固醇特别低的人群，比“好”胆固醇高的人群，更可能携带导致遗传性低“好”胆固醇的基因变异。“好”胆固醇指的是血液中的高密度胆固醇，“好”胆固醇低的人得冠状动脉硬化的可能性更高。这个结果显示，常见疾病不一定总是和常见的基因变异有关，可能是罕见基因变异的强的表型效果。
Multiple Rare Alleles Contribute to Low Plasma Levels of HDL Cholesterol
Heritable variation in complex traits is generally considered to be conferred by common DNA sequence polymorphisms. We tested whether rare DNA sequence variants collectively contribute to variation in plasma levels of highdensity lipoprotein cholesterol (HDL-C). We sequenced three candidate genes (ABCA1, APOA1, and LCAT) that cause Mendelian forms of low HDL-C levels in individuals from a population-based study. Nonsynonymous sequence variants were significantly more common (16% versus 2%) in individuals with low HDL-C (<fifth percentile) than in those with high HDL-C (>95th percentile). Similar findings were obtained in an independent population, and biochemical studies indicated that most sequence variants in the low HDL-C group were functionally important. Thus, rare alleles with major phenotypic effects contribute significantly to low plasma HDL-C levels in the general population.
