School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an 710061, China.
Nutrients. 2023 Jun 30;15(13):2985. doi: 10.3390/nu15132985.
Dysregulation of lipid metabolism has been implicated in age-related macular degeneration (AMD), the leading cause of blindness among the elderly. Lecithin cholesterol acyltransferase (LCAT) is an important enzyme responsible for lipid metabolism, which could be regulated by DNA methylation during the development of various age-related diseases. This study aimed to assess the association between LCAT DNA methylation and the risk of AMD, and to examine whether plasma vitamin and carotenoid concentrations modified this association. A total of 126 cases of AMD and 174 controls were included in the present analysis. LCAT DNA methylation was detected by quantitative real-time methylation-1specific PCR (qMSP). Circulating vitamins and carotenoids were measured using reversed-phase high-performance liquid chromatography (RP-HPLC). DNA methylation of LCAT was significantly higher in patients with AMD than those in the control subjects. After multivariable adjustment, participants in the highest tertile of LCAT DNA methylation had a 5.37-fold higher risk (95% CI: 2.56, 11.28) of AMD compared with those in the lowest tertile. Each standard deviation (SD) increment of LCAT DNA methylation was associated with a 2.23-fold (95% CI: 1.58, 3.13) increased risk of AMD. There was a J-shaped association between LCAT DNA methylation and AMD risk (P = 0.03). Higher concentrations of plasma retinol and β-cryptoxanthin were significantly associated with decreased levels of LCAT DNA methylation, with the multivariate-adjusted β coefficient being -0.05 (95% CI: -0.08, -0.01) and -0.25 (95% CI: -0.42, -0.08), respectively. In joint analyses of LCAT DNA methylation and plasma vitamin and carotenoid concentrations, the inverse association between increased LCAT DNA methylation and AMD risk was more pronounced among participants who had a lower concentration of plasma retinol and β-cryptoxanthin. These findings highlight the importance of comprehensively assessing LCAT DNA methylation and increasing vitamin and carotenoid status for the prevention of AMD.
脂质代谢失调与年龄相关性黄斑变性（AMD）有关，AMD 是老年人致盲的主要原因。卵磷脂胆固醇酰基转移酶（LCAT）是一种重要的脂质代谢酶，它在各种与年龄相关疾病的发展过程中可能受到 DNA 甲基化的调节。本研究旨在评估 LCAT DNA 甲基化与 AMD 风险的相关性，并研究血浆维生素和类胡萝卜素浓度是否修饰了这种相关性。本研究共纳入了 126 例 AMD 患者和 174 例对照。采用实时定量甲基化-1 特异性 PCR（qMSP）检测 LCAT DNA 甲基化。采用反相高效液相色谱法（RP-HPLC）测定循环维生素和类胡萝卜素。AMD 患者的 LCAT DNA 甲基化水平显著高于对照组。经多变量调整后，LCAT DNA 甲基化水平最高 tertile 的参与者患 AMD 的风险比最低 tertile 的参与者高 5.37 倍（95%CI：2.56，11.28）。LCAT DNA 甲基化每增加一个标准差（SD），AMD 的发病风险增加 2.23 倍（95%CI：1.58，3.13）。LCAT DNA 甲基化与 AMD 风险之间呈“J”形关系（P=0.03）。较高的血浆视黄醇和β-隐黄质浓度与 LCAT DNA 甲基化水平降低显著相关，多元调整后的β系数分别为-0.05（95%CI：-0.08，-0.01）和-0.25（95%CI：-0.42，-0.08）。在 LCAT DNA 甲基化和血浆维生素和类胡萝卜素浓度的联合分析中，在血浆视黄醇和β-隐黄质浓度较低的参与者中，LCAT DNA 甲基化增加与 AMD 风险之间的负相关更为明显。这些发现强调了全面评估 LCAT DNA 甲基化和增加维生素和类胡萝卜素状态对预防 AMD 的重要性。
