Genome-wide analysis of polymorphism × sodium interaction effect on blood pressure identifies a novel 3′-BCL11B gene desert locus

Tsuyoshi Hachiya, Akira Narita, Hideki Ohmomo, Yoichi Sutoh, Shohei Komaki, Kozo Tanno, Mamoru Satoh, Kiyomi Sakata, Jiro Hitomi, Motoyuki Nakamura, Kuniaki Ogasawara, Masayuki Yamamoto, Makoto Sasaki, Atsushi Hozawa, Atsushi Shimizu

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3 Citations (Scopus)

Abstract

Excessive sodium intake is a global risk factor for hypertension. Sodium effects on blood pressure vary from person to person; hence, high-risk group targeting based on personal genetic information can play a complementary role to ongoing population preventive approaches to reduce sodium consumption. To identify genetic factors that modulate sodium effects on blood pressure, we conducted a population-based genome-wide interaction analysis in 8,768 Japanese subjects, which was >3 times larger than a similar previous study. We tested 7,135,436 polymorphisms in the discovery cohort, and loci that met suggestive significance were further examined in an independent replication cohort. We found that an interaction between a novel 3′-BCL11B gene desert locus and daily sodium consumption was significantly associated with systolic blood pressure in both discovery and replication cohorts under the recessive model. Further statistical analysis of rs8022678, the sentinel variant of the 3′-BCL11B gene desert locus, showed that differences in mean systolic blood pressure between high and low sodium consumption subgroups were 5.9 mm Hg (P = 8.8 × 10−12) in rs8022678 A carriers and −0.3 mm Hg (P = 0.27) in rs8022678 A non-carriers, suggesting that the rs8022678 genotype can classify persons into sodium-sensitive (A carriers) and sodium-insensitive (A non-carriers) subgroups. Our results implied that rs8022678 A carriers may receive a greater benefit from sodium-lowering interventions than non-carriers.

Original languageEnglish
Article number14162
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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    Hachiya, T., Narita, A., Ohmomo, H., Sutoh, Y., Komaki, S., Tanno, K., Satoh, M., Sakata, K., Hitomi, J., Nakamura, M., Ogasawara, K., Yamamoto, M., Sasaki, M., Hozawa, A., & Shimizu, A. (2018). Genome-wide analysis of polymorphism × sodium interaction effect on blood pressure identifies a novel 3′-BCL11B gene desert locus. Scientific reports, 8(1), [14162]. https://doi.org/10.1038/s41598-018-32074-1