The interaction between ABCA1 polymorphism and physical activity on the HDL-cholesterol levels in a Japanese population

• Published in: Journal of lipid research 2020-01, Vol.61 (1), p.86-94
• Main Authors: Nishida, Yuichiro, Hachiya, Tsuyoshi, Hara, Megumi, Shimanoe, Chisato, Tanaka, Keitaro, Sutoh, Yoichi, Shimizu, Atsushi, Hishida, Asahi, Tsukamoto, Mineko, Kadomatsu, Yuka, Oze, Isao, Koyanagi, Yuriko N., Kuriyama, Nagato, Koyama, Teruhide, Ibusuki, Rie, Takezaki, Toshiro, Ikezaki, Hiroaki, Furusyo, Norihiro, Takashima, Naoyuki, Kadota, Aya, Uemura, Hirokazu, Katsuura-Kamano, Sakurako, Suzuki, Sadao, Nakagawa-Senda, Hiroko, Kuriki, Kiyonori, Mikami, Haruo, Nakamura, Yohko, Momozawa, Yukihide, Kubo, Michiaki, Nakatochi, Masahiro, Naito, Mariko, Wakai, Kenji
• Format: Article
• Language: English
• Subjects: adenosine 5′-triphosphate binding cassette transporter A1; Adult; Aged; Alleles; ATP Binding Cassette Transporter 1 - genetics; cholesterol efflux; Cholesterol, HDL - blood; Cholesterol, HDL - genetics; Cholesterol, HDL - metabolism; epidemiology; exercise; Female; genetics; high density lipoprotein-cholesterol; Humans; Japan; Male; Middle Aged; Patient-Oriented and Epidemiological Research; Polymorphism, Single Nucleotide - genetics; polymorphisms
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.P091546

Few studies have investigated the interactions between HDL-C-related SNPs identified by genome-wide association (GWA) study and physical activity (PA) on HDL-C. First, we conducted a sex-stratified GWA study in a discovery sample (2,231 men and 2,431 women) and replication sample (2,599 men and 3,109 women) to identify SNPs influencing log-transformed HDL-C in Japanese participants in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. We also replicated previously reported HDL-C-related SNPs in a combined (discovery plus replication) sample (4,830 men and 5,540 women). We then analyzed the interactions of the HDL-C-related SNPs with PA on HDL-C. The sex-stratified GWA analyses identified 11 and 10 HDL-C-related SNPs in men and women as targets for an interaction analysis. Among these, only one interaction of ABCA1 rs1883025 with PA was statistically significant in men, after Bonferroni correction [P-interaction = 0.001 (α = 0.05/21 = 0.002)]. The per-major-allele (C allele) increase in log-transformed HDL-C was lost in men with low PA (β = 0.008) compared with those with medium (β = 0.032) or high PA (β = 0.034). These findings suggest that the benefit of carrying a C allele of ABCA1 rs1883025 on enhancing HDL-C may be attenuated in inactive men.