MDM2基因单核苷酸多态性309（MDM2 SNP309）对年轻健康女性和男性的心肺适能有不同影响。

The MDM2 SNP309 differentially impacts cardiorespiratory fitness in young healthy women and men.

作者信息

Haddadi Ghazal, Lam Brian, Akhtar Sokaina, Yavelberg Loren, Jamnik Veronica, Roudier Emilie

机构信息

School of Kinesiology and Health Science, Faculty of Health, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada.

出版信息

Eur J Appl Physiol. 2025 May;125(5):1371-1383. doi: 10.1007/s00421-024-05682-1. Epub 2024 Dec 16.

DOI:10.1007/s00421-024-05682-1

PMID:39681743

Abstract

PURPOSE

Maximal oxygen consumption (VOmax), the predominant index of cardiorespiratory fitness (CRF), is a predictor of whole-body function and longevity in humans. The central cardiac function and the skeletal muscle's capacity to use oxygen are key determinants of VOmax. Murine Double Minute 2 (MDM2), mainly known as an oncogene, could regulate myocardial hypertrophy, skeletal muscle angiogenesis, and oxidative phosphorylation. A prevalent single nucleotide polymorphism in the MDM2 promoter (SNP309) substitutes a T for a G, supporting a greater transcriptional activity. We aim to assess whether SNP309 impacts intrinsic CRF.

METHODS

82 young healthy nonathletic male and female adults aged 23 ± 2 years performed cardiorespiratory exercise testing to determine their VOmax (mL kg min). The genomic DNAs isolated from saliva were genotyped using Taqman-based qPCR.

RESULTS

A one-way ANOVA showed that SNP309 influenced relative VOmax in the whole cohort (p = 0.044) and in men (p = 0.009), remaining non-significant in women (p = 0.133). VOmax was higher in TT homozygotes than in GT heterozygotes (whole cohort, 47 ± 12 vs. 42 ± 6 mL kg min, p = 0.030; men, 53 ± 8 vs. 45 ± 6 mL kg min, p = 0.011). A contingency analysis revealed a positive association between SNP309 in men in which the TT genotype was more frequent in the high VOmax group (p = 0.006). When considering G as the dominant allele, men bearing a G allele had lower relative VOmax than TT homozygotes (47 ± 7 vs. 53 ± 8, GG/GT vs. TT, p = 0.010). Conversely, women bearing a G allele had a higher relative VOmax than TT homozygotes (39 ± 5 vs. 34 ± 7, GG/GT vs. TT, p = 0.047).

CONCLUSION

SNP309 impacts VOmax in a sex-dependent manner in our cohort.

摘要

目的

最大摄氧量（VOmax）是心肺适能（CRF）的主要指标，是人体全身功能和寿命的预测指标。心脏中心功能和骨骼肌利用氧气的能力是VOmax的关键决定因素。鼠双微体2（MDM2）主要作为一种癌基因，可调节心肌肥大、骨骼肌血管生成和氧化磷酸化。MDM2启动子中一种常见的单核苷酸多态性（SNP309）用T替代了G，支持更高的转录活性。我们旨在评估SNP309是否影响内在CRF。

方法

82名年龄在23±2岁的年轻健康非运动员成年男性和女性进行了心肺运动测试，以确定他们的VOmax（毫升/千克/分钟）。使用基于Taqman的定量聚合酶链反应对从唾液中分离的基因组DNA进行基因分型。

结果

单因素方差分析显示，SNP309影响整个队列（p = 0.044）和男性（p = 0.009）的相对VOmax，在女性中无统计学意义（p = 0.133）。TT纯合子的VOmax高于GT杂合子（整个队列，47±12 vs. 42±6毫升/千克/分钟，p = 0.030；男性，53±8 vs. 45±6毫升/千克/分钟，p = 0.011）。列联分析显示男性中SNP309与VOmax呈正相关，其中TT基因型在高VOmax组中更常见（p = 0.006）。当将G视为显性等位基因时，携带G等位基因的男性相对VOmax低于TT纯合子（47±7 vs. 53±8，GG/GT vs. TT，p = 0.010）。相反，携带G等位基因的女性相对VOmax高于TT纯合子（39±5 vs. 34±7，GG/GT vs. TT，p = 0.047）。