探討臺灣男女性運動、APOA5 rs662799及DNA甲基化程度的相關性研究

APOA5 rs662799在過去研究中大多與血脂異常(三酸甘油脂)被共同探討，而且 rs662799也已經被證實是心血管疾病的預測因子。然而，國內外皆鮮少有研究同時針對rs662799基因型和APOA5啟動子甲基化程度進行探討，因此，本研究利用臺灣人體生物資料庫探討臺灣男女性APOA5 rs662799與APOA5啟動子甲基化程度之間的相關性，並進一步依運動種類分層，探討沒運動、有氧運動及非有氧運動的rs662799基因型分布情況及其對APOA5啟動子甲基化程度差異、而導致甲基化程度的異常影響APOA5基因功能表現。本研究資料取自中央研究院臺灣人體生物資料庫(Taiwan Biobank)，2008-2016年間共有884位年齡介於30-70歲參與者納入研究分析(男性464人，女性420人)；使用多變項線性迴歸模式(Multiple linear regression model)計算APOA5 rs662799基因型變異對其啟動子甲基化程度影響之參數估計值(beta coefficient)，所有模式中皆調整年齡、生活習慣、體位測量指標及生化檢驗值等干擾因子。調整干擾因子後，以APOA5 rs662799 AA型為參考組，男性帶有AG型及GG型，APOA5啟動子甲基化之參數估計值分別為153.63及379.94，女性為239.97及338.63，皆達統計顯著意義；進一步依運動種類分層後發現，男性沒運動且帶有APOA5 rs662799 AG型及GG型，APOA5啟動子甲基化之參數估計值分別為170.68及440.43、有氧運動為142.04及341.46，皆達統計顯著差異，而男性非有氧運動為121.83及160.56，未達統計顯著差異；女性沒運動且帶有APOA5 rs662799 AG型及GG型，APOA5啟動子甲基化之參數估計值分別為233.82及341.32、有氧運動為266.50及421.14，達統計顯著差異。本研究結果顯示，不論男女性，帶有rs662799 AG及GG基因型皆會顯著增加APOA5啟動子甲基化程度。利用運動種類分層後，發現男女性運動習慣為沒運動及有氧運動，帶有rs662799 AG及GG基因型皆會顯著增加APOA5啟動子甲基化程度；而男性運動習慣為非有氧運動，帶有rs662799 AG及GG基因型與APOA5啟動子甲基化程度則未達統計顯著意義，未來應再透過更多資料加以驗證之。

關鍵字

APOA5 ；心血管疾病；基因型； DNA甲基化；臺灣人體生物資料庫；運動

並列摘要

APOA5 rs662799 is a novel dyslipidemia-associated locus specifically used to predict cardiovascular diseases. However, few studies have focused on the association of APOA5 rs662799 genotypes and promoter methylation levels. Thus, this study was conducted to investigate the association between APOA5 rs662799 genotypes and promoter methylation levels, as well as to explore whether higher APOA5 promoter methylation levels are linked with a higher risk of dyslipidemia or cardiovascular diseases. Using Taiwan Biobank data which was provided by Academia Sinica, we recruited 884 Taiwan Biobank participants aged 30-70 years with complete genetic data and sociodemographic information. The multivariate linear regression analyses were used to assess the impact of rs662799 genotypes on APOA5 promoter methylation levels. After adjusting for age, lifestyle factors, body measurements and biochemical values, APOA5 promoter methylation levels increased in both men and women. Furthermore, among men who were engaged in no exercise, aerobic exercise and non-aerobic exercise, the beta coefficient (β) of APOA5 promoter methylation levels was 170.68 (p<0.0001) and 440.43 (p<0.0001); 142.04 (p=0.0032) and 341.46 (p=0.0005); and 121.83 (p=0.4625) and 160.56 (p=0.6078) for the AG and GG genotypes, respectively. Likewise, among women with no exercise and aerobic exercise, the beta coefficient (β) was 233.82 (p<0.0001) and 341.32 (p<0.0001); and 266.50 (p<0.0001) and 421.14 (p<0.0001), respectively. Based on our findings, APOA5 promoter methylation levels increased in both men and women with different rs662799 genotypes. More investigations with large sample sizes are needed to clarify the interaction between rs662799 and different exercise types.