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

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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)

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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
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