Interaction of ATP2B1-eNOS pathway gene polymorphisms and lifestyle factors on high blood pressure among adolescents
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摘要:
目的 探索ATP2B1-eNOS通路基因多态性对血压表型的基因-生活方式交互作用, 为阐明青少年血压偏高的发生机制提供线索。 方法 采用方便整群抽样设计, 于2019年7-8月对3所初中872名学生进行问卷调查、人体指标测量和血液样本收集。在外周血液样本提取DNA后, 对基因多态性(ATP2B1/rs17249754和rs2070759, eNOS/rs1799983和rs2070744)进行基因分型。采用Logistic回归分析基因多态性与血压表型之间的关联并纳入交互项分析基因多态性与生活方式交互作用。 结果 青少年血压偏高的检出率为9.52%(男生9.15%, 女生9.87%), 性别差异无统计学意义(χ2=0.13, P=0.72)。男生和女生之间年龄、收缩压、舒张压、体质量指数(BMI)分类、出生体重、每日在校体育锻炼时间与每日在家玩电子游戏时间差异均有统计学意义(P值均 < 0.05)。Logistic回归分析显示, eNOS/rs2070744多态性在隐性模型下与血压偏高存在关联, 且CC基因型携带者相较于TT/TC基因型携带者血压偏高的发生风险升高(OR=3.88, 95%CI=1.00~15.02, P < 0.05)。基因-生活方式交互作用结果显示, ATP2B1/rs2070759多态性与在校体育锻炼时间对血压偏高存在交互作用(P交互=0.05)。在每日在校体育锻炼时间 < 1 h亚组中, TT/TG基因型携带者相较于GG基因型携带者会增加血压偏高发生风险(OR=2.65, 95%CI=1.11~6.30, P < 0.05);而每日在校体育锻炼时间≥1 h亚组中, 与血压偏高无相关性。 结论 eNOS/rs2070744多态性与青少年血压偏高相关, ATP2B1/rs2070759多态性与在校体育锻炼时间对血压偏高存在交互作用。青少年应增加在校体育锻炼时间, 这将有助于高血压易感者维持正常的血压水平。 Abstract:Objective To explore the gene-lifestyle interaction of ATP2B1-eNOS pathway gene polymorphisms on blood pressure. Methods Using the convenient cluster sampling method, a total of 872 junior middle school students from 3 school in July to August 2019, were included in the final analysis.The survey included questionnaire investigation, anthropometry measurement and blood sample collection.After DNA was extracted from peripheral blood samples, the gene polymorphisms (ATP2B1 gene rs17249754 and rs2070759, eNOS gene rs1799983 and rs2070744) were genotyped.Logistic regression model was used to analyze the association between gene polymorphism and blood pressure phenotypes. Results The prevalence of high blood pressure was 9.52% in adolescents (9.15% in boys and 9.87% in girls), with no significant sex difference (χ2=0.13, P=0.72).There were statistically significant differences between boys and girls in age, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) classification, birth weight, daily school physical exercise time and daily playing video games time (P < 0.05).Logistic regression analysis showed that, eNOS gene rs2070744 polymorphism was associated with high blood pressure (HBP) under the recessive model, and the risk of HBP in CC genotype carriers were higher than that TT/TC genotype carriers (OR=3.88, 95%CI=1.00-15.02, P < 0.05).The results of gene-lifestyle interaction showed that ATP2B1 gene rs2070759 polymorphism gene had an interaction with the time of physical exercise in school (Pinteraction=0.05).In the subgroup with daily physical exercise time at school < 1 hour, the TT/TG genotype carriers were associated with increased risk of HBP compared with GG genotype carriers (OR=2.65, 95%CI=1.11-6.30, P < 0.05).But in the subgroup with daily physical exercise time in school ≥1 hour, rs2070759 was not significantly associated with HBP. Conclusion eNOS/rs2070744 polymorphisms are associated with risk of HBP among adolescents.There is significant interaction between ATP2B1 gene rs2070759 polymorphism and physical exercise time in school on HBP.Adolescents should spend more time on physical activity in school, which will help to maintain normal blood pressure level. -
Key words:
- Genes, Blood pressure /
- Regression analysis /
- Adolescent
1) 利益冲突声明 所有作者声明无利益冲突。2) 黄泽华与谢铭为共同第一作者。 -
表 1 ATP2B1和eNOS基因多态性与血压偏高的关联分析(n=872)
Table 1. Association between ATP2B1 gene polymorphisms, eNOS gene polymorphisms and risk of high blood pressure(n=872)
SNP和遗传模型 基因型 分组 人数 血压偏高人数 血压偏高率/% OR值(OR值95%CI) AIC值 ATP2B1/rs17249754 显性模型 AA 112 10 8.93 1.00 508.44 AG+GG 756 73 9.66 1.07(0.52~2.22) 隐性模型 AA+AG 501 42 8.38 1.00 505.94 GG 367 41 11.17 1.47(0.92~2.36) 加性模型 - 868 83 9.56 1.26(0.88~1.80) 506.85 ATP2B1/rs2070759 显性模型 GG 230 17 7.39 1.00 507.77 GT+TT 641 66 10.30 1.43(0.80~2.54) 隐性模型 GG+GT 642 60 9.35 1.00 509.04 TT 229 23 10.04 1.15(0.68~1.95) 加性模型 - 871 83 9.53 1.20(0.86~1.66) 508.18 eNOS/rs1799983 显性模型 TT 11 1 9.09 1.00 508.27 TG+GG 856 82 9.58 1.63(0.19~14.28) 隐性模型 TT+TG 190 16 8.42 1.00 508.28 GG 677 67 9.90 1.15(0.64~2.06) 加性模型 - 867 83 9.57 1.15(0.68~1.97) 508.20 eNOS/rs2070744 显性模型 TT 690 63 9.13 1.00 509.22 TC+CC 181 20 11.05 1.10(0.63~1.93) 隐性模型 TT+TC 859 80 9.31 1.00 506.26 CC 12 3 25.00 3.88(1.00~15.02)* 加性模型 - 871 83 9.53 1.24(0.76~2.02) 508.65 注： *P < 0.05。 
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表 2 ATP2B1基因多态性与血压偏高关联的分层分析(n=872)
Table 2. Stratified analysis of association between ATP2B1 gene polymorphisms and high blood pressure by lifestyle factors(n=872)
自变量 分层因素 rs17249754 rs2070759 基因型 OR值(OR值95%CI) P交互值 基因型 OR值(OR值95%CI) P交互值 喂养方式 母乳喂养 25/23/8 1.31(0.73~2.35) 0.16 13/30/13 1.24(0.63~2.44) 0.17 218/249/70 1.00 139/252/148 1.00 非母乳喂养 13/4/2 3.13(1.06~9.20)* 7/10/2 4.16(0.77~22.65) 64/63/18 1.00 37/70/39 1.00 每日在校体育锻炼时间/h < 1 29/18/5 2.03(1.10~3.77)* 0.23 15/30/7 2.65(1.11~6.30)* 0.05 189/203/53 1.00 119/212/117 1.00 ≥1 11/11/5 1.03(0.45~2.35) 7/11/9 0.77(0.32~1.83) 115/134/41 1.00 74/135/81 1.00 每日在家玩电子游戏 < 1 19/17/6 1.27(0.65~2.46) 0.27 11/22/9 1.31(0.59~2.91) 0.63 时间/h 183/194/56 1.00 116/207/111 1.00 ≥1 21/12/4 2.14(1.04~4.38)* 12/18/7 1.80(0.72~4.48) 122/146/39 1.00 77/144/88 1.00 注： ATP2B1/rs17249754多态性的分析采用隐性遗传模型(AA+AG基因型=0，GG基因型=1)，ATP2B1/rs2070759多态性选择显性遗传模型(GG基因型=0，TG+TT基因型=1)；*P < 0.05。
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表 3 eNOS基因多态性与血压偏高关联的分层分析
Table 3. Stratified analysis of association between eNOS gene polymorphisms and high blood pressure by lifestyle factors
自变量 分层因素 rs1799983 rs2070744 基因型 OR值(OR值95%CI) P交互值 基因型 OR值(OR值95%CI) P交互值 喂养方式 母乳喂养 46/9/1 1.40(0.72~2.73) 0.73 13/30/13 4.23(0.79~22.83) 0.74 412/116/7 1.00 2/11/43 1.00 非母乳喂养 16/3/0 1.16(0.36~3.77) 6/101/432 2.70(0.25~29.00) 116/27/3 1.00 1/5/13 1.00 每日在校体育锻炼时间/h < 1 42/9/1 1.01(0.52~1.97) 0.24 3/35/108 6.01(1.04~34.66)* 0.55 353/90/5 1.00 2/11/39 1.00 ≥1 23/4/0 2.01(0.69~5.89) 4/101/344 2.34(0.26~21.53) 216/65/5 1.00 1/4/22 1.00 每日在家玩电子游戏 < 1 32/9/1 0.89(0.46~1.74) 0.11 5/45/239 2.04(0.23~18.05) 0.32 时间/h 336/89/7 1.00 1/8/33 1.00 ≥1 33/4/0 2.53(0.86~7.44) 6/90/337 7.88(1.19~52.12)* 238/66/3 1.00 2/7/28 1.00 注： eNOS/rs1799983分析采用加性遗传模型，eNOS/rs2070744分析采用隐性遗传模型(TT+TC基因型=0，CC基因型=1)；*P < 0.05。
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[1] MILLS K T, STEFANESCU A, HE J. The global epidemiology of hypertension[J]. Nat Rev Nephrol, 2020, 16(4): 223-237. doi: 10.1038/s41581-019-0244-2 [2] 祁欢, 张庆华, 陈婷. 国内外儿童青少年高血压研究现状[J]. 中国儿童保健杂志, 2020, 28(4): 416-418, 422. https://www.cnki.com.cn/Article/CJFDTOTAL-ERTO202004017.htmQI H, ZHANG Q H, CHEN T. Current status of research on hypertension in children and adolescents[J]. Chin J Child Health Care, 2020, 28(4): 416-418, 422. https://www.cnki.com.cn/Article/CJFDTOTAL-ERTO202004017.htm [3] SUN X M, YANG M, JIANG C X. Association of ATP2B1 gene polymorphism with incidence of eclampsia[J]. Eur Rev Med Pharmacol Sci, 2019, 23(24): 10609-10616. [4] ALTHWAB S A, AHMED A A, RASHEED Z, et al. ATP2B1 genotypes rs2070759 and rs2681472 polymorphisms and risk of hypertension in Saudi population[J]. Nucleosid Nucleotid Nucl Acids, 2021, 40(11): 1075-1089. doi: 10.1080/15257770.2021.1973034 [5] SALARI N, BOKAEE S, FARSHCHIAN N, et al. The role of polymorphisms rs2070744 and rs1799983 eNOS gene in patients with POAG: a systematic review and Meta-analysis[J]. Int Ophthalmol, 2021, 41(8): 2747-2763. doi: 10.1007/s10792-021-01832-y [6] LONG Y, CHEN S W, GAO C L, et al. ATP2B1 gene silencing increases NO production under basal conditions through the Ca2+/calmodulin/eNOS signaling pathway in endothelial cells[J]. Hyperten Res, 2018, 41(4): 246-252. doi: 10.1038/s41440-018-0012-x [7] SHI J, LIU S, GUO Y, et al. Association between eNOS rs1799983 polymorphism and hypertension: a Meta-analysis involving 14, 185 cases and 13, 407 controls[J]. BMC Cardiovasc Disord, 2021, 21(1): 385. doi: 10.1186/s12872-021-02192-2 [8] XU J, QIAN H X, HU S P, et al. Gender-specific association of ATP2B1 variants with susceptibility to essential hypertension in the Han Chinese population[J]. Biomed Res Int, 2016(7): 1910565. [9] MIYAKI K, TOHYAMA S, MURATA M, et al. Salt intake affects the relation between hypertension and the T-786C polymorphism in the endothelial nitric oxide synthase gene[J]. Am J Hhyperten, 2005, 18(12 Pt 1): 1556-1562. [10] YANG Y D, SONG J Y, WANG S, et al. Combined effects of the rs9810888 polymorphism in calcium voltage-gated channel subunit alpha1 D (CACNA1D) and lifestyle behaviors on blood pressure level among Chinese children[J]. PLoS One, 2019, 14(5): e0216950. doi: 10.1371/journal.pone.0216950 [11] 国家卫生健康委员会. 7~18岁儿童青少年血压偏高筛查界值: WS/T 610—2018[S]. 2018-12-01.National Health Commission of the PRC. Reference of screening for elevated blood pressure among children and adolescents aged 7-18 years: WS/T 610-2018[S]. 2018-12-01. [12] SAMARANI S, DUPONT-LUCAS C, MARCIL V, et al. CpG methylation in TGFβ1 and IL-6 genes as surrogate biomarkers for diagnosis of IBD in children[J]. Inflamm Bowel Dis, 2020, 26(10): 1572-1578. doi: 10.1093/ibd/izaa074 [13] PETKEVICIENE J, KLUMBIENE J, SIMONYTE S, et al. Physical, behavioural and genetic predictors of adult hypertension: the findings of the Kaunas Cardiovascular Risk Cohort study[J]. PLoS One, 2014, 9(10): e109974. doi: 10.1371/journal.pone.0109974 [14] OLSON S, WANG M G, CARAFOLI E, et al. Localization of two genes encoding plasma membrane Ca2(+)-transporting ATPases to human chromosomes 1q25-32 and 12q21-23[J]. Genomics, 1991, 9(4): 629-641. doi: 10.1016/0888-7543(91)90356-J [15] ALTHWAB S A, AHMED A A, RASHEED Z, et al. ATP2B1 genotypes rs2070759 and rs2681472 polymorphisms and risk of hypertension in Saudi population[J]. Nucleosides Nucleotides Nucleic Acids, 2021, 40(11): 1075-1089. doi: 10.1080/15257770.2021.1973034 [16] SOMBIÉ H K, KOLOGO J K, TCHELOUGOU D, et al. Positive association between ATP2B1 rs17249754 and essential hypertension: a case-control study in Burkina Faso, West Africa[J]. BMC Cardiovasc Disord, 2019, 19(1): 155. doi: 10.1186/s12872-019-1136-x [17] VANE J R, ANGGẬRD E E, BOTTING R M. Regulatory functions of the vascular endothelium[J]. New England J Med, 1990, 323(1): 27-36. doi: 10.1056/NEJM199007053230106 [18] JEMAA R, KALLEL A, SEDIRI Y, et al. Association between-786TC polymorphism in the endothelial nitric oxide synthase gene and hypertension in the Tunisian population[J]. Experim Molecular Pathol, 2011, 90(2): 210-214. doi: 10.1016/j.yexmp.2010.12.006 [19] HYNDMAN M E, PARSONS H G, VERMA S, et al. The T-786-->C mutation in endothelial nitric oxide synthase is associated with hypertension[J]. Hypertension, 2002, 39(4): 919-922. doi: 10.1161/01.HYP.0000013703.07316.7F [20] BAKKER E A, SUI X, BRELLENTHIN A G, et al. Physical activity and fitness for the prevention of hypertension[J]. Curr Opin Cardiol, 2018, 33(4): 394-401. doi: 10.1097/HCO.0000000000000526 [21] HERRERA N A, JESUS I, SHINOHARA A L, et al. Exercise training attenuates dexamethasone-induced hypertension by improving autonomic balance to the heart, sympathetic vascular modulation and skeletal muscle microcirculation[J]. J Hyperten, 2016, 34(10): 1967-1976. doi: 10.1097/HJH.0000000000001032 -
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