Abstract
Aims: The effects of inhibition of sodium glucose cotransporter (SGLT)-1, as opposed to SGLT2, on cardiovascular structure and function are not well known. We assessed the associations of a missense genetic variant of SGLT1 with cardiac structure and function. Methods and results: We evaluated associations of a functionally modifying variant of SLC5A1 (rs17683011 [p.Asn51Ser]), the gene that encodes SGLT1, with cardiac structure and function on echocardiography among middle-aged adults in the Coronary Artery Risk Development in Young Adults Study. Of 1904 participants (55.3 ± 3.5 years, 57% female, 34% Black), 166 (13%) White participants and 18 (3%) Black participants had at least one copy of rs17683011. There were no significant differences in age, sex, body mass index, glucose, or diabetes status by the presence of the rs17683011 variant. In Black participants, the presence of at least one copy of the rs17683011 variant was significantly associated with better GLS compared with those without a copy of the variant after covariate adjustment (−15.8 ± 0.7% vs. −14.0 ± 0.1%, P = 0.02). Although the direction of effect was consistent, the association between the presence of at least one copy of rs17683011 and GLS was not statistically significant in White participants (−15.1 ± 0.2% vs. −14.8 ± 0.1%, P = 0.16). There were no significant associations between rs17683011 and other measures of LV structure, systolic function, or diastolic function. Conclusions: The rs17683011 variant, a functionally modifying variant of the SGLT1 gene, was associated with higher GLS among middle-age adults. These exploratory findings require further validation and suggest that SGLT1 inhibition may have beneficial effects upon LV systolic function.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1496-1501 |
| Number of pages | 6 |
| Journal | ESC Heart Failure |
| Volume | 9 |
| Issue number | 2 |
| DOIs | |
| State | Published - Apr 2022 |
Funding
The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN268201800007I), Northwestern University (HHSN268201800003I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I). GWAS genotyping was funded in part by grants U01‐HG004729 and R01‐HL093029 from the National Institutes of Health to Dr. Myriam Fornage. CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra‐agency agreement between NIA and NHLBI (AG0005). This research was supported by grant KL2TR001424 from the National Center for Advancing Translational Sciences of the National Institutes of Health. This manuscript has been reviewed by CARDIA for scientific content. Dr. Muthiah Vaduganathan has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Relypsa, and Roche Diagnostics, speaker engagements with Novartis and Roche Diagnostics, and participates on clinical endpoint committees for studies sponsored by Galmed and Novartis. Dr. Sanjiv Shah has received research grants from Actelion, AstraZeneca, Corvia, and Novartis, and consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer‐Ingelheim, Cardiora, Eisai, Ironwood, Merck, MyoKardia, Novartis, Sanofi, and United Therapeutics. The remaining authors have nothing to disclose.
Keywords
- Echocardiography
- Genetics
- Heart failure
- Sodium-glucose cotransporter 1
- Subclinical
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
