Email Alert | RSS

Journal of Peking University (Health Sciences) ›› 2023, Vol. 55 ›› Issue (3): 400-407. doi: 10.19723/j.issn.1671-167X.2023.03.003

Previous Articles     Next Articles

Genotype-environment interaction on arterial stiffness: A pedigree-based study

Xue-heng WANG1,Si-yue WANG1,He-xiang PENG1,Meng FAN1,Huang-da GUO1,Tian-jiao HOU1,Meng-ying WANG1,Yi-qun WU1,Xue-ying QIN1,Xun TANG1,Jin LI1,Da-fang CHEN1,Yong-hua HU1,Tao WU1,2,*()   

  1. 1. Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China
    2. Key Laboratory of Epidemiology of Major Diseases, Ministry of Education, Beijing 100191, China
  • Received:2023-03-01 Online:2023-06-18 Published:2023-06-12
  • Contact: Tao WU E-mail:twu@bjmu.edu.cn
  • Supported by:
    the National Natural Science Foundation of China(82204135);the Beijing Natural Science Foundation(7232237);the China Postdoctoral Science Foundation(BX2021021);the China Postdoctoral Science Foundation(2022M710249)

RICH HTML

   

PDF (PC)

Abstract:

Objective: To utilized the baseline data of the Beijing Fangshan Family Cohort Study, and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects. Methods: Probands and their relatives from 9 rural areas in Fangshan district, Beijing were included in this study. We developed a healthy lifestyle score based on five lifestyle behaviors: smoking, alcohol consumption, body mass index (BMI), dietary pattern, and physical activity. The measurements of arterial stiffness were brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). A variance component model was used to determine the heritability of arterial stiffness. Genotype-environment interaction effects were performed by the maximum likelihood methods. Subsequently, 45 candidate single nucleotide polymorphisms (SNPs) located in the glycolipid metabolism pathway were selected, and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles. Results: A total of 6 302 study subjects across 3 225 pedigrees were enrolled in this study, with a mean age of 56.9 years and 45.1% male. Heritability of baPWV and ABI was 0.360 (95%CI: 0.302-0.418) and 0.243 (95%CI: 0.175-0.311), respectively. Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed. Following the findings of genotype-environment interaction analysis, we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness, indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness. Three SNPs in CDKAL1, ATP8B2 and SLC30A8 were shown to interact with BMI, implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness. Conclusion: The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness. Furthermore, we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness. Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness. This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.

Key words: Arterial stiffness, Gene-environment interaction, Lifestyle, Pedigree

CLC Number: 

  • R394

Table 1

Baseline characteristics of participants"

Items Low-risk lifestyle factors P
0-1 2-3 4-5
Total, n (%) 887 (14.1) 3 886 (61.7) 1 529 (24.3)
Male, n (%) 762 (85.9) 1 799 (46.3) 281 (18.4) < 0.01
Age/years, ${\bar x}$±s 55.28±11.30 56.88±10.71 57.84±9.48 < 0.01
baPWV/(cm/s), ${\bar x}$±s 1 675.20±350.82 1 690.77±381.67 1 687.54±386.26 0.54
SBP/mmHg, ${\bar x}$±s 138.17±19.33 136.65±20.37 135.39±19.53 < 0.01
DBP/mmHg, ${\bar x}$±s 84.78±15.79 81.20±14.68 79.34±10.90 < 0.01
ABI, ${\bar x}$±s 1.09±0.10 1.08±0.11 1.08±0.11 0.07
Educational levels, n (%) < 0.01
  Primary school or less 323 (36.4) 1 549 (39.9) 614 (40.1)
  Middle school 426 (48.0) 1 693 (43.6) 635 (41.5)
  High school or above 138 (15.6) 644 (16.6) 280 (18.3)
Hypertension, n (%) 635 (71.6) 2 558 (65.8) 1002 (65.5) < 0.01
Diabetes, n (%) 314 (35.4) 1 643 (42.3) 854 (55.9) < 0.01
Antihypertensive treatment, n (%) 350 (39.5) 1 704 (43.8) 751 (49.1) < 0.01
Diabetes mellitus treatment, n (%) 187 (21.1) 1 156 (29.7) 687 (44.9) < 0.01
Lipid-lowering treatment, n (%) 92 (10.4) 505 (13.0) 255 (16.7) < 0.01

Figure 1

Effect of genotype-environment interaction on arterial stiffness"

Table 2

Effect of gene-healthy diet interaction on baPWV"

Variants Reference/Effect allele EAF Adherence to a healthy dietary pattern* P for interaction
No Yes
ADAMTS9-AS2 rs4607103 T/C 0.58 1.30 (1.06-1.60) 0.89 (0.78-1.03) 0.002
CDH13 rs7193788 G/A 0.53 1.23 (1.00-1.52) 0.90 (0.79-1.04) 0.01

Table 3

Effect of gene-BMI interaction on ABI"

Variants Reference/Effect allele EAF BMI group* P for interaction
Q1 Q2 Q3
CDKAL1 rs7756992 A/G 0.53 0.71 (0.55-0.92) 1.27 (1.03-1.57) 1.01 (0.78-1.32) < 0.001
ATP8B2 rs67156297 A/G 0.89 0.74 (0.50-1.09) 0.99 (0.69-1.41) 1.60 (0.91-2.80) 0.002
SLC30A8 rs3802177 T/C 0.64 0.73 (0.56-0.95) 0.97 (0.77-1.21) 0.99 (0.76-1.30) 0.01
1 Chirinos JA , Segers P , Hughes T , et al. Large-artery stiffness in health and disease: JACC state-of-the-art review[J]. J Am Coll Cardiol, 2019, 74 (9): 1237- 1263.
doi: 10.1016/j.jacc.2019.07.012
2 Boutouyrie P , Chowienczyk P , Humphrey JD , et al. Arterial stiffness and cardiovascular risk in hypertension[J]. Circ Res, 2021, 128 (7): 864- 886.
doi: 10.1161/CIRCRESAHA.121.318061
3 Willum-Hansen T , Staessen JA , Torp-Pedersen C , et al. Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population[J]. Circulation, 2006, 113 (5): 664- 670.
doi: 10.1161/CIRCULATIONAHA.105.579342
4 Mitchell GF , Hwang SJ , Vasan RS , et al. Arterial stiffness and cardiovascular events[J]. Circulation, 2010, 121 (4): 505- 511.
doi: 10.1161/CIRCULATIONAHA.109.886655
5 Kim M , Yoo HJ , Lee HJ , et al. Longitudinal interaction between APOA-1131T>C and overweight in the acceleration of age-related increase in arterial stiffness through the regulation of circulating triglycerides[J]. Hypertens Res, 2019, 42 (2): 241- 248.
doi: 10.1038/s41440-018-0137-y
6 Choi S , Jung S , Kim MK , et al. Gene and dietary calcium interaction effects on brachial-ankle pulse wave velocity[J]. Clin Nutr, 2016, 35 (5): 1127- 1134.
doi: 10.1016/j.clnu.2015.08.009
7 Fung TT , Chiuve SE , McCullough ML , et al. Adherence to a DASH-style diet and risk of coronary heart disease and stroke in women[J]. Arch Intern Med, 2008, 168 (7): 713- 720.
doi: 10.1001/archinte.168.7.713
8 Li Y , Schoufour J , Wang DD , et al. Healthy lifestyle and life expectancy free of cancer, cardiovascular disease, and type 2 diabetes: Prospective cohort study[J]. BMJ, 2020, 368, l6669.
9 张存泰, 陶军, 田小利, 等. 血管衰老临床评估与干预中国专家共识(2018)[J]. 中华老年病研究电子杂志, 2019, 6 (1): 1- 8.
doi: 10.3877/cma.j.issn.2095-8757.2019.01.001
10 Arnett DK , Blumenthal RS , Albert MA , et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: A report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines[J]. J Am Coll Cardiol, 2019, 74 (10): e177- e232.
doi: 10.1016/j.jacc.2019.03.010
11 Mitchell GF , Verwoert GC , Tarasov KV , et al. Common genetic variation in the 3'-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk: The AortaGen Consortium[J]. Circ Cardiovasc Genet, 2012, 5 (1): 81- 90.
doi: 10.1161/CIRCGENETICS.111.959817
12 Fung K , Ramirez J , Warren HR , et al. Genome-wide association study identifies loci for arterial stiffness index in 127, 121 UK Biobank participants[J]. Sci Rep, 2019, 9 (1): 9143.
doi: 10.1038/s41598-019-45703-0
13 Rode M , Teren A , Wirkner K , et al. Genome-wide association analysis of pulse wave velocity traits provide new insights into the causal relationship between arterial stiffness and blood pressure[J]. PLoS One, 2020, 15 (8): e0237237.
doi: 10.1371/journal.pone.0237237
14 Poveda A , Chen Y , Brändström A , et al. The heritable basis of gene-environment interactions in cardiometabolic traits[J]. Diabetologia, 2017, 60 (3): 442- 452.
doi: 10.1007/s00125-016-4184-0
15 Martin LJ , Kissebah AH , Sonnenberg GE , et al. Genotype-by-smoking interaction for leptin levels in the metabolic risk complications of obesity genes project[J]. Int J Obes Relat Metab Disord, 2003, 27 (3): 334- 340.
doi: 10.1038/sj.ijo.0802232
16 Sun K , Xiang X , Li N , et al. Gene-diet interaction between SIRT6 and soybean intake for different levels of pulse wave velocity[J]. Int J Mol Sci, 2015, 16 (7): 14338- 14352.
17 Boesgaard TW , Gjesing AP , Grarup N , et al. Variant near ADAMTS9 known to associate with type 2 diabetes is related to insulin resistance in offspring of type 2 diabetes patients: EUGENE2 study[J]. PLoS One, 2009, 4 (9): e7236.
doi: 10.1371/journal.pone.0007236
18 Berria R , Wang L , Richardson DK , et al. Increased collagen content in insulin-resistant skeletal muscle[J]. Am J Physiol Endocrinol Metab, 2006, 290 (3): E560- 565.
doi: 10.1152/ajpendo.00202.2005
19 Hwang CL , Muchira J , Hibner BA , et al. Alcohol consumption: A new risk factor for arterial stiffness?[J]. Cardiovasc Toxicol, 2022, 22 (3): 236- 245.
doi: 10.1007/s12012-022-09728-8
20 Chung CM , Lin TH , Chen JW , et al. A genome-wide association study reveals a quantitative trait locus of adiponectin on CDH13 that predicts cardiometabolic outcomes[J]. Diabetes, 2011, 60 (9): 2417- 2423.
doi: 10.2337/db10-1321
21 Antoniades C , Antonopoulos AS , Tousoulis D , et al. Adiponectin: From obesity to cardiovascular disease[J]. Obes Rev, 2009, 10 (3): 269- 279.
doi: 10.1111/j.1467-789X.2009.00571.x
22 Jo J , Sull JW , Park EJ , et al. Effects of smoking and obesity on the association between CDH13 (rs3865188) and adiponectin among Korean men: The KARE study[J]. Obesity, 2012, 20 (8): 1683- 1687.
doi: 10.1038/oby.2011.128
23 Li YY , Wang LS , Lu XZ , et al. CDKAL1 gene rs7756992 A/G polymorphism and type 2 diabetes mellitus: A meta-analysis of 62, 567 subjects[J]. Sci Rep, 2013, 3 (1): 3131.
doi: 10.1038/srep03131
24 Imamura M , Takahashi A , Yamauchi T , et al. Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes[J]. Nature Communications, 2016, 7 (1): 10531.
doi: 10.1038/ncomms10531
25 Lin Y , Li P , Cai L , et al. Association study of genetic variants in eight genes/loci with type 2 diabetes in a Han Chinese population[J]. BMC Med Genet, 2010, 11 (1): 97.
doi: 10.1186/1471-2350-11-97
26 Koskeridis F , Evangelou E , Said S , et al. Pleiotropic genetic architecture and novel loci for C-reactive protein levels[J]. Nat Commun, 2022, 13 (1): 6939.
doi: 10.1038/s41467-022-34688-6
[1] Huameng TANG,Dianqi YUAN,Mingxing WANG,Hanbing YANG,Chao GUO. Sequential mediating role of digital participation and health lifestyle in the relationship between socioeconomic status and depression of older adults [J]. Journal of Peking University (Health Sciences), 2024, 56(2): 230-238.
[2] Yi-hua LIU,Qing-ping YUN,Lan-chao ZHANG,Xiao-yue ZHANG,Yu-ting LIN,Fang-jing LIU,Zhi-jie ZHENG,Chun CHANG. Joint association of sedentary behavior and physical activity on anxiety tendency among occupational population in China [J]. Journal of Peking University (Health Sciences), 2022, 54(3): 490-497.
[3] Hong-chen ZHENG,En-ci XUE,Xue-heng WANG,Xi CHEN,Si-yue WANG,Hui HUANG,Jin JIANG,Ying YE,Chun-lan HUANG,Yun ZHOU,Wen-jing GAO,Can-qing YU,Jun LV,Xiao-ling WU,Xiao-ming HUANG,Wei-hua CAO,Yan-sheng YAN,Tao WU,Li-ming LI. Bivariate heritability estimation of resting heart rate and common chronic disease based on extended pedigrees [J]. Journal of Peking University (Health Sciences), 2020, 52(3): 432-437.
[4] WU Gui-jie, MA Shuai, ZHENG Lian-wen, XU Ying, MENG Fan-he, DAI Xiao-wei. A complex chromosome translocation with male infertility of karyotype analysis and literature review [J]. Journal of Peking University(Health Sciences), 2018, 50(4): 729-731.
[5] CHENG Lan, LI Qin, SONG Yi, MA Jun, WANG Hai-Jun. Association of physical activities, sedentary behaviors with overweight/obesity in 9-11 year-old Chinese primary school students [J]. Journal of Peking University(Health Sciences), 2016, 48(3): 436-441.
[6] YUAN Yuan, WANG Ping, WU-CHOU Yah-huei YE Xiao-qian, HUANG Shang-zhi, SHI Bing, WANG Ke, WANG Zhu-qing, LIU Dong-jing, WANG Zi-fan9,WU Tao, WANG Hong. Association study between candidate genes involved in cell-cell adhesion and non-syndromic cleft lip with or without cleft palate in Chinese population [J]. Journal of Peking University(Health Sciences), 2016, 48(3): 403-408.
[7] WEI Dong-Mei, WU Li-Jing, GAO Ai-Yu, LI Qin, CHENG Lan, WANG Hai-Jun. Study on the relations among the screen-based sedentary behaviors, family factors and body mass index of children [J]. Journal of Peking University(Health Sciences), 2015, 47(3): 390-394.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright © Journal of Peking University (Health Sciences), All Rights Reserved.
Powered by Beijing Magtech Co. Ltd