Gender Specificity and Local Socioeconomic Influence on Association of GHR fl/d3 Polymorphism With Growth and Metabolism in Children and Adolescents

Xiaotian Chen; Chunlan Liu; Song Yang; Yaming Yang; Yanchun Chen; Xianghai Zhao; Weiguang Zhu; Qihui Zhao; Chuan Ni; Xiangyuan Huang; Weili Yan; Chong Shen; Harvest F Gu

doi:10.3389/fped.2022.546080

Gender Specificity and Local Socioeconomic Influence on Association of GHR fl/d3 Polymorphism With Growth and Metabolism in Children and Adolescents

Front Pediatr. 2022 Mar 23:10:546080. doi: 10.3389/fped.2022.546080. eCollection 2022.

Authors

Xiaotian Chen¹, Chunlan Liu², Song Yang³, Yaming Yang⁴, Yanchun Chen³, Xianghai Zhao³, Weiguang Zhu⁵, Qihui Zhao⁵, Chuan Ni⁵, Xiangyuan Huang¹, Weili Yan¹, Chong Shen², Harvest F Gu⁶

Affiliations

¹ Department of Clinical Epidemiology, Children's Hospital of Fudan University, Shanghai, China.
² Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
³ Department of Cardiology, People's Hospital of Yixing City, Affiliated Yixing People's Hospital of Jiangsu University, Yixing, China.
⁴ Center for Disease Control and Prevention of Yixing City, Yixing, China.
⁵ Center for Disease Control and Prevention of Suqian City, Suqian, China.
⁶ School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.

Abstract

Objective: Growth hormone receptor (GHR) mediates most GH biological actions. This study is aimed to evaluate whether GHR fl/d3 polymorphism contributes to the inter-individual variability of growth and metabolism in healthy children and adolescents.

Methods: A total of 4,730 students aged 6-16 years from Yixing and Suqian City in China were included in this cross-sectional study. Height and body mass index (BMI) were transformed into the form of z-score corresponding to age and gender. Logistic regression was used to evaluate the associations of GHR fl/d3 polymorphism with height, BMI, metabolic traits, and hypertension by estimating the odds ratios (ORs) and 95% confidence intervals (CIs).

Results: GHR d3 allele was inversely associated with overweight, total cholesterol (TC) and triglyceride (TG) levels (OR [95% CI] for overweight: 0.754 [0.593-0.959], P = 0.021; OR [95% CI] for TC: 0.744 [0.614-0.902], P = 0.003; OR [95% CI] for TG: 0.812 [0.654-0.998], P = 0.047). GHR d3 allele was associated with decreased odds of pre-hypertension in boys (OR [95% CI]: 0.791 [0.645-0.971], P = 0.025), but associated with increased odds of pre-hypertension and hypertension in girls (ORs [95% CIs]: 1.379 [1.106-1.719], P = 0.004; OR [95% CI]: 1.240 [1.013-1.519], P = 0.037). Interaction of GHR fl/d3 polymorphism with gender contributed to increased odds of pre-hypertension and hypertension (interactive ORs [95% CIs]: 1.735 [1.214-2.481], P = 0.003; OR [95% CI]: 1.509 [1.092-2.086], P = 0.013). Stratification analysis showed that the correlation tendencies of GHR fl/d3 polymorphism and BMI with age were different between two cities with discrepant economic development levels.

Conclusion: GHR fl/d3 polymorphism is associated with growth, metabolism, and hypertension in children and adolescents with the gender specificity, and the genetic effect of GHR fl/d3 may be modified by the local socioeconomic levels.

Keywords: GHR fl/d3 polymorphism; gender specificity; growth hormone receptor; metabolism; socioeconomic levels.