Kamboh M I, Bunker C H, Aston C E, Nestlerode C S, McAllister A E, Ukoli F A
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15261, USA.
Genet Epidemiol. 1999;16(2):205-22. doi: 10.1002/(SICI)1098-2272(1999)16:2<205::AID-GEPI7>3.0.CO;2-P.
Genetic studies carried out mainly in European and European-derived populations have shown that common polymorphisms in genes coding for apolipoproteins are significant determinants of serum lipoprotein-lipid levels variation. However, except for a few sporadic studies, the distribution of apolipoprotein polymorphisms and their association with serum lipoprotein-lipid levels have not been evaluated systematically in African or African-derived populations. In this investigation we have studied five apolipoprotein polymorphisms, including APOA1/MspI-75 bp, APOA1/MspI+83 bp, APOC3/PvuII, APOE, and APOH in 786 Africans (493 men, 293 women) from Nigeria. The sample is comprised of Nigerian civil servants consisting of 462 junior staff (less affluent) and 324 senior staff (more affluent) where staff status is a correlate of their socioeconomic status. We first examined genetic associations in the total sample stratified by gender to determine the role of apolipoprotein polymorphisms in affecting serum lipid profile in the general population, and then by staff status to evaluate possible gene-environment interactions. In the total sample, the APOC3/PvuII polymorphism showed significant effect on HDL-cholesterol (P = 0.029) and HDL3-cholesterol (P = 0.009) in women, and the APOE polymorphism was significantly associated with total cholesterol (P = 0.031) and LDL-cholesterol (P = 0.0006) in women. Multiple regression analyses showed that the APOC3/PvuII polymorphism accounts for about 2 and 3% of the variation in HDL-cholesterol and HDL3-cholesterol, respectively, in women; while the APOE polymorphism accounted for about 5 and 6% of the variation in total- and LDL-cholesterol, respectively, in women. Whereas the association of the APOE polymorphism was independent of the staff status, the significant affect of the APOC3/PvuII polymorphism on HDL- and HDL3-cholesterol was confined to senior staff women where it explained about 7% of their variation. We also observed an interaction between staff and the APOH polymorphism in affecting cholesterol levels. The APOH polymorphism showed significant association with total cholesterol (P = 0.010) and LDL-cholesterol (P = 0.016) in senior staff women and explained about 7 and 5% of their phenotypic variations, respectively. These data indicate that gene-environment interaction may play an important role in affecting serum lipid profile in African populations.
主要在欧洲及欧洲裔人群中开展的基因研究表明,编码载脂蛋白的基因中的常见多态性是血清脂蛋白 - 脂质水平变化的重要决定因素。然而,除了少数零星研究外,载脂蛋白多态性的分布及其与血清脂蛋白 - 脂质水平的关联在非洲或非洲裔人群中尚未得到系统评估。在本研究中,我们对来自尼日利亚的786名非洲人(493名男性,293名女性)的5种载脂蛋白多态性进行了研究,包括APOA1/MspI - 75 bp、APOA1/MspI + 83 bp、APOC3/PvuII、APOE和APOH。样本由尼日利亚公务员组成,其中包括462名初级职员(较不富裕)和324名高级职员(较富裕),职员身份与他们的社会经济地位相关。我们首先按性别对总样本进行分层检查基因关联,以确定载脂蛋白多态性在影响一般人群血清脂质谱中的作用,然后按职员身份进行评估,以探讨可能的基因 - 环境相互作用。在总样本中,APOC3/PvuII多态性对女性的高密度脂蛋白胆固醇(HDL - 胆固醇,P = 0.029)和HDL3 - 胆固醇(P = 0.009)有显著影响,APOE多态性与女性的总胆固醇(P = 0.031)和低密度脂蛋白胆固醇(P = 0.0006)显著相关。多元回归分析表明,APOC3/PvuII多态性分别解释了女性HDL - 胆固醇和HDL3 - 胆固醇变异的约2%和3%;而APOE多态性分别解释了女性总胆固醇和低密度脂蛋白胆固醇变异的约5%和6%。虽然APOE多态性的关联与职员身份无关,但APOC3/PvuII多态性对HDL - 胆固醇和HDL3 - 胆固醇的显著影响仅限于高级职员女性,该多态性解释了她们约7%的变异。我们还观察到职员身份与APOH多态性在影响胆固醇水平方面存在相互作用。APOH多态性与高级职员女性的总胆固醇(P = 0.010)和低密度脂蛋白胆固醇(P = 0.016)显著相关,分别解释了她们约7%和5%的表型变异。这些数据表明,基因 - 环境相互作用可能在影响非洲人群血清脂质谱中起重要作用。