目的 探讨镁代谢相关基因多态性对中国中老年人群血浆镁状况的影响及基因-膳食交互作用。方法 基于2015年中国成人慢性病与营养监测数据,采用分层随机抽样选取2431名≥45岁研究对象;通过SNPscan技术检测TRPM6 rs2274924、CNNM2 rs3740393、CLDN9 rs719676和FXYD2 rs948100基因型;采用ICP-MS测定血浆镁浓度;使用多元线性回归和Logistic回归分析基因型与血浆镁水平及缺乏风险的关联,并检验基因型与膳食镁摄入状态（充足/不足）的交互作用,模型校正性别、年龄、BMI、民族、教育程度、城乡、地域及膳食镁摄入状态。结果 研究人群血浆镁中位数为0.87 mmol/L, CNNM2 rs3740393 CC基因型与较高的血浆镁水平相关（β=0.019,95%CI: 0.002-0.036,P=0.028）;FXYD2 rs948100 CG基因型与较低的镁缺乏风险相关（OR=0.386,95%CI: 0.161-0.925,P=0.033）;交互作用分析显示,TRPM6 rs2274924与膳食镁充足状态存在显著交互作用（TT×充足: β=0.052,95%CI: 0.024-0.081,P-FDR=0.003;CT×充足: β=0.039,95%CI: 0.010~0.069,P-FDR=0.034）,其TT及CT基因携带者的血浆镁水平显著增高。结论 中国中老年人群中CNNM2和FXYD2基因变异是血浆镁状况的独立影响因素,而TRPM6基因变异与膳食摄入存在交互作用。
Abstract
Objective To investigate the effects of magnesium metabolism-related gene polymorphisms on plasma magnesium status and their interaction with dietary magnesium intake in Chinese adults aged 45 years and above. Methods This study utilized data from the 2015 China Nutrition and Health Surveillance. A total of 2,431 participants aged ≥45 years were selected using stratified random sampling. Genotyping for TRPM6 rs2274924, CNNM2 rs3740393, CLDN9 rs719676, and FXYD2 rs948100 was performed using the SNPscan technique. Plasma magnesium concentration was determined by inductively coupled plasma mass spectrometry (ICP-MS). Multiple linear regression and logistic regression models were employed to assess the associations between genotypes and plasma magnesium levels as well as the risk of magnesium deficiency, respectively. The interaction between genotypes and dietary magnesium intake status (adequate/inadequate) was tested. All models were adjusted for sex, age, body mass index (BMI), ethnicity, education level, residence (urban/rural), region (east/central/west), and dietary magnesium intake status. Results The median plasma magnesium concentration of the study population was 0.87 mmol/L. The CC genotype of CNNM2 rs3740393 was associated with higher plasma magnesium levels (β=0.019, 95% CI: 0.002-0.036, P=0.028). The CG genotype of FXYD2 rs948100 was associated with a lower risk of magnesium deficiency (OR=0.386, 95% CI: 0.161-0.925, P=0.033). Interaction analysis revealed a significant interaction between TRPM6 rs2274924 and adequate dietary magnesium intake (TT×adequate: β=0.052, 95%CI: 0.024-0.081, P-FDR=0.003; CT × adequate: β=0.039, 95% CI: 0.010-0.069, P-FDR=0.034). Plasma magnesium levels were significantly higher in carriers of the TT and CT genotypes. Conclusion This study confirms in a middle-aged and elderly Chinese population that CNNM2 and FXYD2 gene variants are independent influencing factors for plasma magnesium status, while the TRPM6 gene variant exhibits an interaction with dietary intake.
关键词
基因多态性 /
中老年人 /
血镁 /
基因-环境相互作用
Key words
genetic polymorphism /
middle-aged and elderly /
plasma magnesium /
gene-environment interaction
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参考文献
[1] De Baaij JH, Hoenderop JG, Bindels RJ.Magnesium in man: implications for health and disease[J]. Physiol Rev, 2015, 95: 1–46.
[2] Nielsen FH.The role of dietary magnesium in cardiovascular disease[J]. Nutrients,2024, 16:4223.
[3] Del Gobbo LC, Imamura F, Wu JH, et al. Circulating and dietary magnesium and risk of cardiovascular disease: a systematic review and meta-analysis of prospective studies[J]. Am J Clin Nutr, 2013, 98: 160–173.
[4] Rosique-Esteban N, Guasch-Ferré M, Hernández-Alonso P, et al. Dietary magnesium and cardiovascular disease: a review with emphasis in epidemiological studies[J]. Nutrients, 2018, 10:168.
[5] Chen F, Wang J, Cheng Y,et al. Magnesium and cognitive health in adults: a systematic review and meta-analysis[J]. Adv Nutr, 2024,15:100272.
[6] Bressendorff I, Hansen D, Schou M, et al. The effect of magnesium supplementation on vascular calcification in CKD: a randomized clinical trial (MAGiCAL-CKD)[J]. J Am Soc Nephrol. 2023,34: 886–894.
[7] Volpe SL.Magnesium in disease prevention and overall health[J]. Adv Nutr, 2013, 4: 378s–383s.
[8] Gao Q, Cil O.Magnesium for disease treatment and prevention: emerging mechanisms and opportunities[J]. Trends Pharmacol Sci,2024,45:708–722.
[9] Meyer TE, Verwoert GC, Hwang SJ, et al. Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six Loci influencing serum magnesium levels[J]. PLoS Genet, 2010, 6:e1001045.
[10] Stuiver M, Lainez S, Will C, et al. CNNM2, encoding a basolateral protein required for renal Mg2+ handling, is mutated in dominant hypomagnesemia[J]. Am J Hum Genet, 2011, 88: 333–343.
[11] Guo D, Zhou Y, Wei X, et al. Preliminary study of genome-wide association identifies novel susceptibi-lity genes for serum mineral elements in the Chinese Han population[J]. Biol Trace Elem Res, 2022, 200: 2549–2555.
[12] Ryazanova LV, Rondon LJ, Zierler S, et al. TRPM7 is essential for Mg2+ homeostasis in mammals[J]. Nat Commun,2010,1: 109.
[13] Schlingmann KP, Weber S, Peters M, et al. Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family[J]. Nat Genet, 2002, 31: 166–170.
[14] Cao Y, Zhen S, Taylor AW, et al. Magnesium intake and sleep disorder symptoms: findings from the Jiangsu nutrition study of Chinese adults at five-year follow-up[J]. Nutrients,2018,10:1354.
[15] 李淑娟, 琚腊红, 张继国, 等. 1982-2015年中国成年居民膳食镁摄入量变化趋势[J]. 卫生研究, 2025, 54: 23–27.
[16] Yang J, Cao Y, Shan X, et al. The magnesium status and suggested reference ranges of plasma magnesium, calcium, and calcium/magnesium ratio in Chinese adults over 45 years old[J]. Nutrients,2023,15:886.
[17] Yu D, Zhao L, Zhang J, et al. China nutrition and health surveys (1982-2017)[J]. China CDC Wkly, 2021, 3:193–195.
[18] Rosanoff A, West C, Elin RJ, et al. Recommendation on an updated standardization of serum magnesium reference ranges[J]. Eur J Nutr, 2022, 61: 3697–3706.
[19] Willett WC, Howe GR, Kushi LH.Adjustment for total energy intake in epidemiologic studies[J]. Am J Clin Nutr,1997,65:1220S–1228S.
[20] 中国营养学会. 中国居民膳食营养素参考摄入量[M]. 2023版. 北京:科学出版社, 2023.
[21] Kieboom BCT, Ligthart S, Dehghan A, et al. Serum magnesium and the risk of prediabetes: a population-based cohort study[J]. Diabetologia, 2017, 60: 843–853.
[22] Hruby A, Ngwa JS, RenstrÖm F, et al. Higher magnesium intake is associated with lower fasting glucose and insulin, with no evidence of interaction with select genetic loci, in a meta-analysis of 15 CHARGE Consortium Studies[J]. J Nutr, 2013, 143: 345–353.
[23] Arystarkhova E, Liu YB, Salazar C, et al. Hyperplasia of pancreatic beta cells and improved glucose tolerance in mice deficient in the FXYD2 subunit of Na,K-ATPase[J]. J Biol Chem, 2013, 288: 7077–7085.
[24] Voets T, Nilius B, Hoefs S,et al. TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption[J]. J Biol Chem,2004,279:19–25.
[25] Manuck SB, McCaffery JM. Gene-environment interaction[J]. Annu Rev Psychol,2014,65:41–70.
[26] Günther T.Concentration, compartmentation and metabolic function of intracellular free Mg2+[J]. Magnes Res,2006,19:225–236.
[27] Hou J, Goodenough DA.Claudin-16 and claudin-19 function in the thick ascending limb[J]. Curr Opin Nephrol Hypertens,2010,19:483–438.
基金
国家重点研发计划“膳食营养评估和干预技术研究”项目（No.2020YFC2006300）; 中国人群重要营养素需要量研究 (No.2020YFC2006302)
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