Population-Based Impact of Smoking, Drinking, and Genetic Factors on HDL-Cholesterol Levels in J-MICC Study Participants.

Yora Nindita,Yuichiro Nishida,Yohko Nakamura,Toshiro Takezaki,Takashi Tamura,Megumi Hara,Rieko Okada,Yukihide Momozawa,Naoko Miyagawa,Mako Nagayoshi,Naoyuki Takashima,Teruhide Koyama,Kenji Wakai,Masahiro Nakatochi,Kenji Takeuchi,Keiichi Shimatani,Haruo Mikami,Asahi Hishida,Hiroaki Ikezaki,Kokichi Arisawa,Etsuko Ozaki,Masayuki Murata,Rie Ibusuki,Michiaki Kubo,Keitaro Matsuo,Hidemi Ito,Takahiro Otani,Daisaku Nishimoto,Ippei Shimoshikiryo,Sadao Suzuki,Kiyonori Kuriki,Sakurako Katsuura-Kamao

doi:10.2188/jea.je20210142

Abstract

Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. However, the population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C. Data from 11,498 men and women aged 35-69 years were collected for a genome-wide association study (GWAS). Sixty-five HDL-C-related SNPs with genome-wide significance (P < 5 × 10-8) were selected from the GWAS catalog, and seven representative SNPs were defined, and the population-based impact was estimated using population attributable fraction (PAF). We found that smoking, drinking, daily activity, habitual exercise, egg intake, BMI, age, sex and the SNPs CETP rs3764261, APOA5 rs662799, LIPC rs1800588, LPL rs328, ABCA1 rs2575876, LIPG rs3786247, and APOE rs429358 were associated with HDL-C levels. The gene-environmental interactions on smoking and drinking were not statistically significant. The PAF for low HDL-C was the highest in men (63.2%) and in rs3764261 (31.5%) of the genetic factors, and the PAFs of smoking and drinking were 23.1% and 41.8%, respectively. The present study showed that the population-based impact of genomic factor CETP rs3764261 for low HDL-C was higher than that of smoking and lower than that of drinking.

Highlights

Low serum levels of HDL-cholesterol (HDL-C) are associated with an increased risk of cardiovascular disease (CVD).[1,2] As clinically available drugs that can enhance HDL-C levels are limited, genetic and environmental factors play an important role in the alleviation of CVD risk
Besides association with single nucleotide polymorphism (SNPs) in reverse cholesterol transport (RCT)-related genes, the association with several other SNPs, such as those in genes encoding endothelial lipase (LIPG) and APOE, which are related to lipoprotein dynamism, has been reported.[10,12]
The subjects (n = 14,555) of the genome-wide association study (GWAS) selected from among the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study participants were aged from 35–69 years and belonged to 11 prefectures of Japan (Chiba, Shizuoka, Aichi, Shiga, Kyoto, Tokushima, Fukuoka, Saga, Nagasaki, Kagoshima, and Okinawa); participants were selected by ten research institutes and universities

Summary

Introduction

Low serum levels of HDL-cholesterol (HDL-C) are associated with an increased risk of cardiovascular disease (CVD).[1,2] As clinically available drugs that can enhance HDL-C levels are limited, genetic and environmental factors play an important role in the alleviation of CVD risk. Alcohol intake, physical activity, BMI, and diet intake have been confirmed to be environmental factors that affect HDL-C levels.[3,4,5,6]. Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. The population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C

Methods

Results

Conclusion