Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, 165 Sechul-Ri, BaeBang-Yup, Asan-Si 336-795, ChungNam-Do, Republic of Korea.
Nutrients. 2023 Apr 4;15(7):1764. doi: 10.3390/nu15071764.
Adult height is inversely related to metabolic syndrome (MetS) risk, but its genetic impacts have not been revealed. The present study aimed to examine the hypothesis that adult height-related genetic variants interact with lifestyle to influence adult height and are associated with MetS risk in adults aged >40 in Korea during 2010-2014. Participants were divided into short stature (SS; control) and tall stature (TS; case) by the 85th percentile of adult height. The genetic variants linked to adult height were screened from a genome-wide association study in a city hospital-based cohort (n = 58,701) and confirmed in Ansan/Ansung plus rural cohorts (n = 13,783) among the Korean Genome and Epidemiology Study. Genetic variants that interacted with each other were identified using the generalized multifactor dimensionality reduction (GMDR) analysis. The interaction between the polygenic risk score (PRS) of the selected genetic variants and lifestyles was examined. Adult height was inversely associated with MetS, cardiovascular diseases, and liver function. The PRS, including zinc finger and BTB domain containing 38 ()_rs6762722, polyadenylate-binding protein-interacting protein-2B ()_rs13034890, carboxypeptidase Z ()_rs3756173, and latent-transforming growth factor beta-binding protein-1 ()_rs4630744, was positively associated with height by 1.29 times and inversely with MetS by 0.894 times after adjusting for covariates. In expression quantitative trait loci, the gene expression of growth/differentiation factor-5 ()_rs224331, non-SMC condensin I complex subunit G ()_rs2074974, ligand-dependent nuclear receptor corepressor like ()_rs7700107, and insulin-like growth factor-1 receptor ()_rs2871865 was inversely linked to their risk allele in the tibial nerve and brain. The gene expression of _rs13034890 and a disintegrin and metalloproteinase with thrombospondin motifs-like-3 ()_rs13034890 was positively related to it. The PRS was inversely associated with MetS, hyperglycemia, HbA1c, and white blood cell counts. The wild type of _rs224331 (Ala276) lowered binding energy with rugosin A, D, and E (one of the hydrolyzable tannins) but not the mutated one (276Ser) in the in-silico analysis. The PRS interacted with energy intake and rice-main diet; PRS impact was higher in the high energy intake and the low rice-main diet. In conclusion, the PRS for adult height interacted with energy intake and diet patterns to modulate height and was linked to height and MetS by modulating their expression in the tibial nerve and brain.
成人身高与代谢综合征（MetS）风险呈负相关，但尚未揭示其遗传影响。本研究旨在检验以下假设：成人身高相关的遗传变异与生活方式相互作用，影响成人身高，并与 2010-2014 年韩国 40 岁以上成年人的 MetS 风险相关。参与者根据成人身高的第 85 百分位分为矮小身材（SS；对照组）和高大身材（TS；病例组）。与成人身高相关的遗传变异从一个城市医院队列的全基因组关联研究中筛选出来（n=58701），并在韩国基因组和流行病学研究中的安山/安城加农村队列中得到确认（n=13783）。使用广义多因子维度降低（GMDR）分析确定相互作用的遗传变异。检查选定遗传变异的多基因风险评分（PRS）与生活方式之间的相互作用。成人身高与 MetS、心血管疾病和肝功能呈负相关。PRS，包括锌指和 BTB 结构域包含 38（）_rs6762722、多聚腺苷酸结合蛋白相互作用蛋白 2B（）_rs13034890、羧肽酶 Z（）_rs3756173 和潜伏转化生长因子β结合蛋白 1（）_rs4630744，与身高呈正相关，调整协变量后，身高增加 1.29 倍，与 MetS 呈负相关，降低 0.894 倍。在表达数量性状基因座中，生长/分化因子-5（）_rs224331、非-SMC 凝聚素 I 复合物亚基 G（）_rs2074974、配体依赖性核受体共抑制因子样（）_rs7700107 和胰岛素样生长因子-1 受体（）_rs2871865 的基因表达与胫骨神经和大脑中它们的风险等位基因呈负相关。_rs13034890 和解整合素和金属蛋白酶与血栓反应蛋白样 3（）_rs13034890 的基因表达呈正相关。PRS 与 MetS、高血糖、HbA1c 和白细胞计数呈负相关。在计算机分析中，野生型 _rs224331（Ala276）与藜芦醇 A、D 和 E（一种可水解单宁）的结合能降低，但突变型（276Ser）则不然。PRS 与能量摄入和以大米为主的饮食相互作用；PRS 影响在高能量摄入和低以大米为主的饮食中更高。总之，成人身高的 PRS 与能量摄入和饮食模式相互作用，调节身高，并通过调节其在胫骨神经和大脑中的表达，与身高和 MetS 相关。
