评估载脂蛋白A-I基因启动子中G到A的替换作为有无胆固醇酯转运蛋白缺乏受试者高密度脂蛋白胆固醇水平决定因素的作用。

Evaluation of G-to-A substitution in the apolipoprotein A-I gene promoter as a determinant of high-density lipoprotein cholesterol level in subjects with and without cholesteryl ester transfer protein deficiency.

作者信息

Akita H, Chiba H, Tsuji M, Hui S P, Takahashi Y, Matsuno K, Kobayashi K

机构信息

Department of Laboratory Medicine, Hokkaido University School of Medicine, Sapporo, Japan.

出版信息

Hum Genet. 1995 Nov;96(5):521-6. doi: 10.1007/BF00197405.

DOI:10.1007/BF00197405

PMID:8529997

Abstract

The effect of a polymorphism, guanine (G) to adenine (A) substitution in the promoter of apolipoprotein A-I gene at a position 78 bp upstream of the transcription initiation site, on the serum high-density lipoprotein (HDL)-cholesterol level was studied in 168 Japanese subjects with HDL-cholesterol levels ranging from 26 to 171 mg/dl. Considering the significant effect of cholesteryl ester transfer protein (CETP) on the HDL-cholesterol level and the common occurrence of its deficiency, we performed statistical analyses separately for two groups: one without CETP deficiency (n = 126) and the other with CETP deficiency (n = 42). In the group without CETP deficiency, in which the numbers of G/G, G/A, and A/A genotypes were 92 (73.0%), 28 (22.2%), and 6 (4.8%), respectively, the frequency of the A allele in the subjects with HDL-cholesterol levels of > or = 70 mg/dl did not differ from subjects with HDL-cholesterol levels of < or = 69 mg/dl, irrespective of gender: 0.154 and 0.145 in males, and 0.182 and 0.174 in females, respectively, for the > or = 70 mg/dl and < or = 69 mg/dl groups. Additionally, the HDL-cholesterol levels for the subjects with the G/G genotype did not differ from those for the subjects with the A allele: 64 +/- 22, 58 +/- 14, 77 +/- 14 and 62 +/- 16 mg/dl, respectively, for the G/G, G/A, A/A, and G/A + A/A in males, and 72 +/- 18, 74 +/- 24, 63 +/- 4, and 73 +/- 23 mg/dl in females. For the group with CETP deficiency, in which the numbers of G/G and G/A + A/A genotypes were 25 (59.5%) and 17 (40.5%), the HDL-cholesterol levels also did not differ: 98 +/- 24 mg/dl and 99 +/- 30 mg/dl, respectively, for the G/G and G/A + A/A genotypes. Thus, there is no evidence that the polymorphism has any effect on serum HDL-cholesterol levels regardless of CETP status. We conclude that the G-to-A substitution in the promoter of apolipoprotein A-I gene does not significantly alter serum HDL-cholesterol level.

摘要

在168名血清高密度脂蛋白（HDL）胆固醇水平在26至171mg/dl之间的日本受试者中，研究了位于转录起始位点上游78bp处的载脂蛋白A-I基因启动子中的一种多态性，即鸟嘌呤（G）到腺嘌呤（A）的替换对血清HDL胆固醇水平的影响。考虑到胆固醇酯转运蛋白（CETP）对HDL胆固醇水平有显著影响且其缺乏情况较为常见，我们将受试者分为两组分别进行统计分析：一组为无CETP缺乏者（n = 126），另一组为有CETP缺乏者（n = 42）。在无CETP缺乏的组中，G/G、G/A和A/A基因型的数量分别为92（73.0%）、28（22.2%）和6（4.8%），HDL胆固醇水平≥70mg/dl的受试者中A等位基因频率与HDL胆固醇水平≤69mg/dl的受试者相比无差异，无论性别如何：≥70mg/dl组和≤69mg/dl组男性分别为0.154和0.145，女性分别为0.182和0.174。此外，G/G基因型受试者的HDL胆固醇水平与携带A等位基因的受试者相比无差异：男性中G/G、G/A、A/A以及G/A + A/A基因型的HDL胆固醇水平分别为64±22、58±14、77±14和62±16mg/dl，女性分别为72±18、74±24、63±4和73±23mg/dl。对于有CETP缺乏的组，G/G和G/A + A/A基因型的数量分别为25（59.5%）和17（40.5%），其HDL胆固醇水平也无差异：G/G和G/A + A/A基因型分别为98±24mg/dl和99±30mg/dl。因此，无论CETP状态如何，均无证据表明该多态性对血清HDL胆固醇水平有任何影响。我们得出结论，载脂蛋白A-I基因启动子中的G到A替换不会显著改变血清HDL胆固醇水平。