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ADRB3 基因的甲基化谱及其与成年人血脂谱和营养状况的关系。

Methylation profile of the ADRB3 gene and its association with lipid profile and nutritional status in adults.

机构信息

Graduate Program in Nutrition Sciences, Health Sciences Center (Centro de Ciências da Saúde, CCS), Federal University of Paraíba (UFPB), João Pessoa, Brazil.

Graduate Program in Molecular and Human Biology, Natural Exact Sciences Center (Centro de Ciências Exatas da Natureza, CCEN), UFPB, João Pessoa, Brazil.

出版信息

Biol Res. 2019 Apr 6;52(1):21. doi: 10.1186/s40659-019-0226-7.

Abstract

BACKGROUND

Defects in DNA methylation have been shown to be associated with metabolic diseases such as obesity, dyslipidemia, and hypercholesterolemia. To analyze the methylation profile of the ADRB3 gene and correlate it with lipid profile, lipid intake, and oxidative stress based on malondialdehyde (MDA) and total antioxidant capacity (TAC), homocysteine and folic acid levels, nutritional status, lifestyle, and socioeconomic variables in an adult population. A cross-sectional epidemiological study representative of the East and West regions of the municipality of João Pessoa, Paraíba state, Brazil, enrolled 265 adults of both genders. Demographic, lifestyle, and socioeconomic questionnaires and a 24-h recall questionnaire were applied by trained interviewers' home. Nutritional and biochemical evaluation (DNA methylation, lipid profile, MDA, TAC, homocysteine and folic acid levels) was performed.

RESULTS

DNA hypermethylation of the ADRB3 gene, analyzed in leukocytes, was present in 50% of subjects and was associated with a higher risk of being overweight (OR 3.28; p = 0.008) or obese (OR 3.06; p = 0.017), a higher waist-hip ratio in males (OR 1.17; p = 0.000), greater intake of trans fats (OR 1.94; p = 0.032), higher LDL (OR 2.64; p = 0.003) and triglycerides (OR 1.81; p = 0.031), and higher folic acid levels (OR 1.85; p = 0.022).

CONCLUSIONS

These results suggest that epigenetic changes in the ADRB3 gene locus may explain the development of obesity and non-communicable diseases associated with trans-fat intake, altered lipid profile, and elevated folic acid. Because of its persistence, DNA methylation may have an impact in adults, in association with the development of non-communicable diseases. This study is the first population-based study of the ADRB3 gene, and the data further support evaluation of ADRB3 DNA methylation as an effective biomarker.

摘要

背景

已有研究表明,DNA 甲基化缺陷与肥胖症、血脂异常和高胆固醇血症等代谢疾病有关。本研究旨在分析 ADRB3 基因的甲基化谱,并根据丙二醛 (MDA) 和总抗氧化能力 (TAC)、同型半胱氨酸和叶酸水平、营养状况、生活方式和社会经济变量,分析其与血脂谱、脂质摄入和氧化应激的相关性,研究对象为巴西帕拉伊巴州若昂佩索阿市东部和西部地区的 265 名成年男女。通过受过培训的家访调查员,采用问卷调查的方式收集研究对象的人口统计学、生活方式和社会经济资料,并进行 24 小时回顾性膳食调查。同时对研究对象进行营养和生化评估(DNA 甲基化、血脂谱、MDA、TAC、同型半胱氨酸和叶酸水平)。

结果

白细胞中 ADRB3 基因的 DNA 超甲基化在 50%的研究对象中存在,且与超重(OR3.28;p=0.008)或肥胖(OR3.06;p=0.017)、男性更高的腰围臀围比值(OR1.17;p=0.000)、更多的反式脂肪摄入(OR1.94;p=0.032)、更高的 LDL(OR2.64;p=0.003)和甘油三酯(OR1.81;p=0.031)以及更高的叶酸水平(OR1.85;p=0.022)相关。

结论

这些结果表明,ADRB3 基因座的表观遗传变化可能解释了与反式脂肪摄入、脂质谱改变和叶酸水平升高相关的肥胖和非传染性疾病的发生。由于其持久性,DNA 甲基化可能对成年人产生影响,与非传染性疾病的发生有关。这是首个关于 ADRB3 基因的基于人群的研究,该数据进一步支持将 ADRB3 DNA 甲基化作为一种有效的生物标志物进行评估。

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