Marasco O, Melina F, Mele E, Quaresima B, Zingone A, Focarelli E, Picciotti E, Martelli M L, Fotino L, Vigna M F
Dipartimento di Medicina Sperimentale e Clinica, Facoltà di Medicina e Chirurgie, Università degli Studi di Reggio Calabria, Catanzaro, Italy.
Hum Genet. 1993 Mar;91(2):169-74. doi: 10.1007/BF00222719.
We analysed the allelic and genotypic frequencies of three restriction fragment length polymorphisms in the region of chromosome 11 encoding apolipoprotein AI and CIII genes in a free-living population from South Italy (Calabria). These markers are located at -2500 and -78 bp from the transcription start site of apolipoprotein AI gene (XmnI and MspI, respectively), and in the 3' untranslated region of apolipoprotein CIII gene (SstI). XmnI and SstI label rare alleles (X2 and S2 indicate the presence of the site), whereas the absence of the MspI site (because of a G to A transition) marks the rare allele, M2. Pairwise linkage disequilibrium analysis was determined. Two significant non-random associations were found: a positive disequilibrium between ApoA1/XmnI and ApoA1/MspI markers (P < 0.0001), and a negative disequilibrium between ApoA1/XmnI and ApoC3/SstI markers (P < 0.05). Statistical analysis showed a significant difference in the S2-M2 haplotype frequency between the group of subjects with serum cholesterol levels in the highest decile (P < 0.005) and the group with serum cholesterol levels below the highest decile. The allelic frequency for each locus showed no significant difference between the two groups for all other metabolic parameters, included total cholesterol serum levels. These haplotypes are a more precise measure of genetic variations in the apolipoprotein cluster and their use should allow the mapping of mutations responsible for high serum cholesterol levels.
我们分析了意大利南部（卡拉布里亚）一个自由生活人群中，11号染色体上编码载脂蛋白AI和CIII基因区域的三种限制性片段长度多态性的等位基因和基因型频率。这些标记分别位于载脂蛋白AI基因转录起始位点的-2500和-78 bp处（分别为XmnI和MspI），以及载脂蛋白CIII基因的3'非翻译区（SstI）。XmnI和SstI标记罕见等位基因（X2和S2表示位点的存在），而MspI位点的缺失（由于G到A的转变）标记罕见等位基因M2。进行了成对连锁不平衡分析。发现了两个显著的非随机关联：ApoA1/XmnI和ApoA1/MspI标记之间存在正不平衡（P < 0.0001），ApoA1/XmnI和ApoC3/SstI标记之间存在负不平衡（P < 0.05）。统计分析表明，血清胆固醇水平处于最高十分位数的受试者组与血清胆固醇水平低于最高十分位数的组之间，S2-M2单倍型频率存在显著差异（P < 0.005）。对于所有其他代谢参数，包括血清总胆固醇水平，两组中每个位点的等位基因频率均无显著差异。这些单倍型是载脂蛋白簇中遗传变异的更精确测量指标，使用它们应有助于定位导致高血清胆固醇水平的突变。
