左室肥大は, 心不全への共通最終経路である。我々はJPDSCのデータベースを用いて健康日本人の心電図で左室重量を反映するV5誘導のR波の起電力(高さ)を規定する遺伝因子をGWASで検討した。RV5に関連しているSNPに関しては独立した日本人集団(長浜コホート研究)を対象に再現性を検討した。その結果, TBX3上のSNPrs7301743は, p=7.635 X 10-8で, minor alleleが一つ入るごとに, RV5が0.1mV減高する傾向にあることが明らかとなった。
We have searched for genetic determinants of left ventricular (LV) mass using values for absolute electrocardiographic QRS voltage in a healthy Japanese population. After adjusting for covariates, the corrected S and R wave voltages in leads V1 and V5 from 2,994 healthy volunteers in the Japan Pharmacogenomics Data Science Consortium (JPDSC) database were subjected to a genome-wide association study. Potential associations were validated by an in silico replication study using an independent Japanese population obtained from the Nagahama Prospective Genome Cohort. We identified a novel association between the lead V5, R wave voltage in Japanese individuals and SNP rs7301743[G], which maps near the gene encoding T-box transcription factor Tbx3. Meta-analysis of two independent Japanese datasets demonstrated a marginally significant association of SNP rs7301743 with a 0.071mV (95% CI, 0.038-0.11mV) shorter R wave amplitude in the V5 lead per minor allele copy (P=7.635 x 10-8).

研究種目 : 挑戦的萌芽研究
研究期間 : 2014～2015
課題番号 : 26670409
研究分野 : 循環器内科(心臓)