Cardiometabolic diseases are complex traits which are influenced by several single nucleotide polymorphisms (SNPs). Thus, analysing the combined effects of multiple gene variants might provide a better understanding of disease risk than using a single gene variant approach. Furthermore, studies have found that the effect of SNPs on cardiometabolic traits can be influenced by lifestyle factors, highlighting the importance of analysing gene-lifestyle interactions. In the present study, we investigated the association of 15 gene variants with cardiometabolic traits and examined whether these associations were modified by lifestyle factors such as dietary intake and physical activity. The study included 110 Minangkabau women [aged 25–60 years and body mass index (BMI) 25.13 ± 4.2 kg/m2] from Padang, Indonesia. All participants underwent a physical examination followed by anthropometric, biochemical and dietary assessments and genetic tests. A genetic risk score (GRS) was developed based on 15 cardiometabolic disease-related SNPs. The effect of GRS on cardiometabolic traits was analysed using general linear models. GRS-lifestyle interactions on continuous outcomes were tested by including the interaction term (e.g. lifestyle factor*GRS) in the regression model. Models were adjusted for age, BMI and location (rural or urban), wherever appropriate. There was a significant association between GRS and BMI, where individuals carrying 6 or more risk alleles had higher BMI compared to those carrying 5 or less risk alleles (P = 0.018). Furthermore, there were significant interactions of GRS with protein intake on waist circumference (WC) and triglyceride concentrations (Pinteraction = 0.002 and 0.003, respectively). Among women who had a lower protein intake (13.51 ± 1.18% of the total daily energy intake), carriers of six or more risk alleles had significantly lower WC and triglyceride concentrations compared with carriers of five or less risk alleles (P = 0.0118 and 0.002, respectively). Our study confirmed the association of GRS with higher BMI and further showed a significant effect of the GRS on WC and triglyceride levels through the influence of a low-protein diet. These findings suggest that following a lower protein diet, particularly in genetically predisposed individuals, might be an effective approach for addressing cardiometabolic diseases among Southeast Asian women.

中文翻译：

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遗传风险评分与饮食蛋白质摄入量对东南亚心脏代谢性状的相互作用

心脏代谢疾病是复杂的特征，受几种单核苷酸多态性（SNP）影响。因此，与使用单个基因变体方法相比，分析多个基因变体的组合作用可能会更好地了解疾病风险。此外，研究发现，SNP对心脏代谢特性的影响可能会受到生活方式因素的影响，从而突出了分析基因与生活方式相互作用的重要性。在本研究中，我们调查了15种基因变异与心脏代谢特征的关联，并检查了这些关联是否被生活方式因素（如饮食摄入和体育锻炼）所修饰。该研究包括来自印度尼西亚巴东的110名Minangkabau妇女[年龄在25至60岁，体重指数（BMI）为25.13±4.2 kg / m2]。所有参与者均接受了身体检查，随后进行了人体测量，生化和饮食评估以及基因检测。基于15种与心脏代谢疾病相关的SNP，制定了遗传风险评分（GRS）。使用通用线性模型分析了GRS对心脏代谢特性的影响。通过将交互作用项（例如，生活方式因子* GRS）包括在回归模型中，来测试GRS与生活方式在连续结果上的交互作用。在适当的情况下，对模型进行了年龄，BMI和位置（农村或城市）调整。GRS与BMI之间存在显着关联，其中携带6个或更多风险等位基因的个体的BMI比携带5个或更少风险等位基因的个体更高（P = 0.018）。此外，GRS与腰围（WC）和甘油三酸酯浓度的蛋白质摄入之间存在显着的相互作用（相互作用分别为0.002和0.003）。在蛋白质摄入量较低（每日总能量摄入量的13.51±1.18％）的女性中，与五个或五个以下风险等位基因的携带者相比，六个或六个以上风险等位基因的携带者的WC和甘油三酯浓度明显降低（P = 0.0118和0.002） ， 分别）。我们的研究证实了GRS与较高的BMI的关联，并进一步显示了GRS通过低蛋白饮食的影响对WC和甘油三酸酯水平的显着影响。这些发现表明，降低蛋白质饮食，特别是在遗传易感人群中，可能是解决东南亚女性心脏代谢疾病的有效方法。