Icon Legend

This session is not in your schedule.

This session is in your schedule. Click again to remove it.

Session: Personalizing Nutrition - Select Genetic, Epigenetic and Microbiome Interactions Influencing Diet and Diet-related Diseases (Oral 13)

(OR13-03-23) The Effect of Genetic Polymorphisms in PIK3CG Gene on the Risk of Lean NAFLD in the Elderly: Mediation by Total Cholesterol

Sunday, July 23, 2023

4:24 PM – 4:36 PM ET

Location: Constitution B

Presenting Author(s)

Na Wu

Post doctor
Shanghai Innovation Center of Traditional Chinese Medicine Health Service, School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Shanghai, Shanghai, China (People's Republic)

Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

Co-Author(s)

NT

Nan Tang

Shanghai Innovation Center of Traditional Chinese Medicine Health Service, School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China
YX

Yalan Xiong

Shanghai Innovation Center of Traditional Chinese Medicine Health Service, School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China
XS

Xinyu Shi

Shanghai Innovation Center of Traditional Chinese Medicine Health Service, School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China
HS

Hualing Song

Shanghai Innovation Center of Traditional Chinese Medicine Health Service, School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China
JW

Jianying Wang

Shanghai Innovation Center of Traditional Chinese Medicine Health Service, School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China
LZ

Lei Zhang

Shanghai Innovation Center of Traditional Chinese Medicine Health Service, School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China
GJ

Guang Ji

Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
BL

Baocheng Liu

Shanghai Innovation Center of Traditional Chinese Medicine Health Service, School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China

Disclosure(s):

Na Wu: No relevant financial relationship(s) with ineligible companies to disclose.

Objectives: Non-alcoholic fatty liver disease (NAFLD) often exists along with obesity; however, quite a few individuals have a body mass index (BMI) within the normal range, and around 20%-40% of the global NAFLD population was classified as lean or non-obese. This study aimed to investigate the mediation effect of total cholesterol (TC) on the association between genetic variation in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG) and the risk of lean NAFLD in the elderly Chinese Han population.

Methods: Lean NAFLD in the present study was defined by BMI < 23.0 kg/m². A total of 750 participants were categorized into four groups: lean NAFLD, lean non-NAFLD, non-lean NAFLD and non-lean non-NAFLD. Five single nucleotide polymorphisms (SNPs) involved in four genes, i.e., brain derived neurotrophic factor (BDNF), PIK3CG, insulin receptor substrate-1 gene (IRS1) and laminin subunit beta 3 (LAMB3) that enriched the PI3K/AKT signaling pathway were included. “SNPassoc” R package was used to analyze the associations of genetic variations with variables in five genetic models, which were rechecked with logistic regression. Mediation models were conducted to explore whether the variable can mediate the association between SNPs and the risk of lean NAFLD.

Results: Lean NAFLD patients had higher serum alanine transaminase, fasting glucose, TC and triglyceride, and lower frequencies of C allele and T allele in PIK3CG rs17477177 than did lean non-NAFLD individuals (p < 0.05). PIK3CG polymorphism rs17477177 was significantly associated with TC under the codominant, dominant, over-dominant, and log-additive models (p < 0.05 for all), and the TT-CC genotypes of PIK3CG rs17477177 polymorphism were statistically related to higher TC (p = 0.008). Notably, TC significantly mediated the association between rs17477177 in PIK3CG with the risk of lean NAFLD (p < 0.05).

Conclusions: In this study, TC mediated the association between PIK3CG rs17477177 and the risk of lean NAFLD. It suggests that altering the concentration of TC may reduce the risk of developing lean NAFLD and provide a better understanding of the genetic etiology of lean NAFLD.

Funding Sources: This work was supported by National Natural Science Foundation of China; Shanghai Health Commission for Traditional Chinese Medicine; China Postdoctoral Science Foundation, No.72 General Fund, 2022.