Genetic variation in sodium glucose co-transporter 1 and cardiac structure and function at middle age

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.

Keywords: Echocardiography; Genetics; Heart failure; Sodium-glucose cotransporter 1; Subclinical.