The relationship between polymorphism rs12449964 of the phosphatidylethanolamine- N-methyltransferase gene and hypertriglyceridemia and obesity in patients with type 2 diabetes

I. Azarova
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引用次数: 1

Abstract

Phosphatidylethanolamine N-methyltransferase (PEMT) is the enzyme of lipid metabolism that catalyzes the conversion of phosphatidylethanolamine to phosphatidylcholine in a series of three methylation reactions. Low activity of the enzyme can increase the availability of phosphatidic acid for triacylglycerol synthesis and thus favor obesity, one of the most important risk factors for type 2 diabetes (T2D). The aim of the study: To study the relationship of the rs12449964 (C>T) in the regulatory region of the PEMT (phosphatidylethanolamine-N-methyltransferase) gene with blood plasma triglycerides, as well as the risk of obesity and T2D in population of Central Russia. Materials and methods: The study included 2060 unrelated individuals of Slavic origin, including 1024 patients with T2D and 1036 healthy volunteers. Genotyping of PEMT gene polymorphism (C>T, rs12449964) was performed by laser desorption / ionization time-of-flight mass spectrometry using the MassArray Analyzer 4 platform (Agena Bioscience). SNPStats online program was used for statistical analysis of the obtained data. Results: Linear regression analysis did not reveal an association of rs12449964 of the PEMT gene with a risk of developing T2D regardless of body mass index (P>0,05). However, the T/T genotype of the studied SNP is associated with an increased risk of obesity in patients with type 2 diabetes (OR 1.66; 95% CI 1.11-2.46; P = 0.011, adjusted for sex and age, recessive model). In addition, carriage of the T/T genotype was associated with a higher level of triacylglycerols in the blood plasma of patients with T2D, both in the presence of obesity and without it (P<0.05). According to GTEx Portal, the rs12449964T allele is associated with decreased PEMT expression in various tissues. Conclusion: The study revealed for the first time the association of rs12449964 of the PEMT gene with hypertriglyceridemia and an increased risk of obesity in patients with T2D, which may be due to the low transcriptional activity of the phosphatidylethanolamine- N-methyltransferase gene in carriers of the alternative allele of the studied SNP.
磷脂酰乙醇胺- n -甲基转移酶基因rs12449964多态性与2型糖尿病患者高甘油三酯血症和肥胖的关系
磷脂酰乙醇胺n -甲基转移酶(PEMT)是一种脂质代谢酶,催化磷脂酰乙醇胺在一系列三次甲基化反应中转化为磷脂酰胆碱。低活性的酶可以增加磷脂酸合成三酰甘油的可用性,从而有利于肥胖,这是2型糖尿病(T2D)最重要的危险因素之一。本研究目的:研究俄罗斯中部人群ppt(磷脂酰乙醇胺- n -甲基转移酶)基因调控区域rs12449964 (C>T)与血浆甘油三酯、肥胖和T2D风险的关系。材料与方法:本研究纳入无血缘关系的斯拉夫裔个体2060例,其中T2D患者1024例,健康志愿者1036例。使用masarray Analyzer 4平台(Agena Bioscience),采用激光解吸/电离飞行时间质谱法对ppt基因多态性(C b> T, rs12449964)进行基因分型。使用SNPStats在线程序对获得的数据进行统计分析。结果:线性回归分析未显示ppt基因rs12449964与发生T2D的风险相关,而与体重指数无关(P>0,05)。然而,所研究的SNP的T/T基因型与2型糖尿病患者肥胖风险增加相关(OR 1.66;95% ci 1.11-2.46;P = 0.011,经性别和年龄调整,为隐性模型)。此外,携带T/T基因型与T2D患者血浆中较高水平的甘油三酯相关,无论是否存在肥胖(P<0.05)。根据GTEx Portal, rs12449964T等位基因与多种组织中ppemt表达减少有关。结论:本研究首次揭示了ppt基因rs12449964与T2D患者高甘油三酯血症和肥胖风险增加的相关性,这可能是由于所研究SNP替代等位基因携带者的磷脂酰乙醇胺- n -甲基转移酶基因转录活性较低所致。
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