Hypertension and Cardiovascular Prevention Center, University of Sassari, Sassari, Italy.
Atherosclerosis. 2009 Nov;207(1):162-7. doi: 10.1016/j.atherosclerosis.2009.04.027. Epub 2009 May 4.
Autosomal recessive hypercholesterolemia (ARH) is a lipid disorder caused by mutations in a specific adaptor protein for the LDL receptor. ARH is rare except in Sardinia where three alleles (ARH1, ARH2 and ARH3) explain most of cases. The prevalence of ARH heterozygotes in Sardinia is not well determined as well as inconclusive data are available on the effect of the ARH carrier status on LDL cholesterol (LDL-C) and coronary risk.
3410 Sardinians (986 blood donors, 1709 with hypertension and 715 with myocardial infarction (MI)) were screened for ARH alleles. For comparison purposes, lipid data of 60 ARH heterozygous carriers and 60 non-carriers identified within 24 ARH families were also considered.
In the whole study cohort, no ARH homozygotes were found, but 15 ARH1 (0.44%) and 9 ARH2 (0.26%) heterozygous carriers were identified. The frequency of ARH alleles in blood donors was 0.0030, not different from that in hypertensive subjects (0.0032). ARH alleles tended to be more common in MI patients (0.0049), but no association between ARH carrier status and MI risk was detected after controlling for conventional risk factors. ARH carriers and non-carriers showed similar LDL-C levels. This result was confirmed when ARH carriers and non-carriers identified throughout family-based and population-based screenings were combined and compared (141.0+/-41 mg/dl vs. 137.0+/-41 mg/dl, respectively; p=0.19).
These data indicate that the frequency of ARH heterozygotes in Sardinia is approximately 1:143 individuals, thus making this condition one of the most common in the Sardinian population. However, ARH carrier status does not influence LDL-C concentration and coronary risk, thus suggesting that ARH can be regarded as a truly recessive disorder.
常染色体隐性高胆固醇血症（ARH）是由 LDL 受体特定衔接蛋白的突变引起的脂质紊乱。除了在撒丁岛，这种疾病非常罕见，在那里，三个等位基因（ARH1、ARH2 和 ARH3）解释了大多数病例。ARH 杂合子在撒丁岛的流行率尚不清楚，并且关于 ARH 携带者状态对 LDL 胆固醇（LDL-C）和冠心病风险的影响，目前尚无定论。
3410 名撒丁岛人（986 名献血者、1709 名高血压患者和 715 名心肌梗死（MI）患者）接受了 ARH 等位基因筛查。为了比较目的，还考虑了在 24 个 ARH 家族中确定的 60 名 ARH 杂合子携带者和 60 名非携带者的血脂数据。
在整个研究队列中，未发现 ARH 纯合子，但发现了 15 名 ARH1（0.44%）和 9 名 ARH2（0.26%）杂合子携带者。献血者中的 ARH 等位基因频率为 0.0030，与高血压患者（0.0032）无差异。ARH 等位基因在 MI 患者中更为常见（0.0049），但在控制传统危险因素后，并未发现 ARH 携带者状态与 MI 风险之间存在关联。ARH 携带者和非携带者的 LDL-C 水平相似。当将通过基于家族和基于人群的筛查确定的 ARH 携带者和非携带者合并并比较时，这一结果得到了证实（分别为 141.0+/-41 mg/dl 和 137.0+/-41 mg/dl；p=0.19）。
这些数据表明，ARH 杂合子在撒丁岛的频率约为 1:143 个体，因此使这种情况成为撒丁岛人群中最常见的情况之一。然而，ARH 携带者状态并不影响 LDL-C 浓度和冠心病风险，因此表明 ARH 可被视为真正的隐性疾病。
