Wilcken D E, Blades B L, Dudman N P
Department of Cardiovascular Medicine, University of New South Wales, Prince Henry Hospital, Sydney, Australia.
J Inherit Metab Dis. 1988;11 Suppl 1:87-90. doi: 10.1007/BF01800573.
We measured by radial immunodiffusion apolipoprotein B (ApoB) as a genetic marker for familial hypercholesterolaemia in heel prick blood spot samples on filter paper routinely collected from 5000 3- to 5-day-old neonates for current screening programmes. Dried blood spot ApoB levels were distributed continuously and were 9% higher in female neonates than in males (0.246 +/- 0.085 versus 0.225 +/- 0.079 g/L of whole blood, mean +/- SD, p less than 0.0001). Neonates of birth weight under 2.5 kg had lower levels than the population mean in both sexes but levels did not change with birth weight within this range; in those with the birth weights greater than 2.5 kg levels increased with increasing birth weight. Sex and birth weight could account for 5.7% of the variability of ApoB. Levels had largely stabilized by day 3 of life. Of parents of neonates whose ApoB levels were among the top 2%, 45 families were available for study when the infants were aged 12.3 +/- 3.3 months. In 6 of these families there was a persisting elevation of ApoB both in the infants (levels greater than 0.7 g/L of whole blood) and in one parent who also had elevated ApoB and a lipid profile of familial hypercholesterolaemia phenotype, results indicating an ascertainment rate of between 1 in 365 and 1 in 830 of the screened population. These studies have defined the variables affecting neonatal ApoB levels and establish that neonatal screening for familial hypercholesterolaemia is feasible. Primary prevention of vascular disease in young families with the gene should be possible with this approach.
我们通过径向免疫扩散法测量了载脂蛋白B（ApoB），将其作为家族性高胆固醇血症的遗传标志物，检测对象是从5000名3至5日龄新生儿足跟采血滤纸干血斑样本，这些样本是为当前筛查项目常规采集的。干血斑ApoB水平呈连续分布，女性新生儿的水平比男性高9%（全血中分别为0.246±0.085与0.225±0.079 g/L，均值±标准差，p<0.0001）。出生体重低于2.5 kg的新生儿，两性的ApoB水平均低于总体均值，但在此范围内ApoB水平不随出生体重变化；出生体重高于2.5 kg的新生儿，ApoB水平随出生体重增加而升高。性别和出生体重可解释ApoB变异性的5.7%。出生后第3天，ApoB水平基本稳定。在ApoB水平处于前2%的新生儿中，当婴儿12.3±3.3个月大时，有45个家庭可供研究。在其中6个家庭中，婴儿（全血水平大于0.7 g/L）及其一位父母的ApoB持续升高，且该父母也有ApoB升高及家族性高胆固醇血症表型的血脂谱，结果表明在筛查人群中确诊率在365分之一至830分之一之间。这些研究明确了影响新生儿ApoB水平的变量，并证实对家族性高胆固醇血症进行新生儿筛查是可行的。采用这种方法，对携带该基因的年轻家庭进行血管疾病的一级预防应是可能的。
