Ehrenborg E, Clee S M, Pimstone S N, Reymer P W, Benlian P, Hoogendijk C F, Davis H J, Bissada N, Miao L, Gagné S E, Greenberg L J, Henry R, Henderson H, Ordovas J M, Schaefer E J, Kastelein J J, Kotze M J, Hayden M R
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2672-8. doi: 10.1161/01.atv.17.11.2672.
Recently, a (t-->g) transition at nucleotide -93 in the lipoprotein lipase (LPL) gene promoter has been observed in Caucasians. Here, we have compared the frequency of the -93g carriers in three distinct populations (Caucasians, South African Blacks, and Chinese). The carrier frequency in the Caucasian population was 1.7% (4/232), which was in contrast to the South African Black population, which had a frequency for this allele of 76.4% (123/161) of the individuals tested. This transition was not observed in the Chinese population under study. Near complete linkage disequilibrium between the -93g and the previously described D9N mutation was observed in the Caucasian population but not in South African Blacks. To further assess the ancestral origins of these DNA changes, DNA haplotyping using a CA repeat 5' to these substitutions was performed. The -93t allele was associated with only a few specific dinucleotide repeat sizes. In contrast, the -93g allele occurred on chromosomes with many different repeat lengths. The broad distribution of repeats on -93g carrying chromosomes, their high frequency in the South African Black population, and the conservation of the -93g allele among different species may suggest that the -93g allele is the ancestral allele on which a transition to t and the D9N mutations arose. The very high frequency of the -93g allele distinct from the N9 allele in a cohort of Black South Africans allowed us to specifically assess the phenotypic effects of the -93g allele on lipids. Individuals homozygous for the g allele at -93 showed mildly decreased triglycerides compared with individuals homozygous for the t allele (1.14 +/- 0.66 mmol/L versus 0.82 +/- 0.3; P = .04). Thus, the -93g allele in this cohort is associated with low plasma triglyceride levels.
最近，在高加索人群中观察到脂蛋白脂肪酶（LPL）基因启动子中核苷酸-93处发生了（t-->g）转换。在此，我们比较了三个不同人群（高加索人、南非黑人和中国人）中-93g携带者的频率。高加索人群中的携带者频率为1.7%（4/232），这与南非黑人人群形成对比，在接受检测的个体中，该等位基因的频率为76.4%（123/161）。在所研究的中国人群中未观察到这种转换。在高加索人群中观察到-93g与先前描述的D9N突变之间几乎完全连锁不平衡，但在南非黑人中未观察到。为了进一步评估这些DNA变化的祖先起源，使用位于这些替换位点5'端的CA重复序列进行了DNA单倍型分析。-93t等位基因仅与少数特定的二核苷酸重复序列大小相关。相比之下，-93g等位基因出现在具有许多不同重复长度的染色体上。携带-93g的染色体上重复序列的广泛分布、它们在南非黑人人群中的高频率以及-93g等位基因在不同物种间的保守性可能表明，-93g等位基因是祖先等位基因，在此基础上发生了向t的转换以及D9N突变。在一群南非黑人中，-93g等位基因与N9等位基因的频率差异很大，这使我们能够具体评估-93g等位基因对脂质的表型影响。与-93位点t等位基因纯合个体相比，-93位点g等位基因纯合个体的甘油三酯水平略有降低（1.14±0.66 mmol/L对0.82±0.3；P = 0.04）。因此，在这一队列中，-93g等位基因与低血浆甘油三酯水平相关。
