Using rare coding variants in SLC5A2 to explore the impact of SGLT2 inhibitors on cardiorenal outcomes
Authors' conclusion
Rare genetic variants in SLC5A2 were associated with increased haemoglobin and decreased uric acid. These variants were also associated with a lower probability of heart failure among participants with T2D, providing tentative genetic support for a cardioprotective effect of SGLT2 inhibition.
Study context
- Population
- European ancestry participants from the UK Biobank with exome sequence and phenotype dataEuropean ancestry participants from the UK Biobank
- Participants
- 442,570 participants
- Comparison
- Association of loss-of-function (LoF) and other rare coding variants in the SLC5A2 gene, as a genetic model of altered SGLT2 function, with 13 cardiometabolic and renal traits and clinical outcomes
- Outcome
- Uric acid
Methodological detailsexome sequence
- Exome sequence
Main finding
As reported in the abstract
Rare variants in SLC5A2 associated with decreased uric acid
PCauchy = 4.98 × 10-13
Further findings
| Outcome | β (95% CI) | P value |
|---|---|---|
| Haemoglobin, frameshift variant rs267607067Increased haemoglobin | 0.33 (0.15–0.51) | P = 2.40 × 10-4 |
| Uric acid, frameshift variant rs768095044Decreased uric acid | −0.31 (−0.49 to −0.13) | P = 4.22 × 10-4 |
Haematocrit
- Rare variants in SLC5A2 associated with increased haematocrit
- PCauchy = 1.67 × 10-5
Haemoglobin
- Rare variants in SLC5A2 associated with increased haemoglobin
- PCauchy = 1.60 × 10-5
Estimated glomerular filtration rate
- Rare variants in SLC5A2 associated with increased estimated glomerular filtration rate
- PCauchy = 9.88 × 10-4
Heart failure, in patients with T2D
- Rare variants within SLC5A2 associated with a lower probability of having heart failure
- PCauchy = 4.00 × 10-4
LoF variants identified in SLC5A2
- LoF variants in SLC5A2 identified
- 52
Original publication
Using rare coding variants in SLC5A2 to explore the impact of SGLT2 inhibitors on cardiorenal outcomes. Eur J Prev Cardiol. Published 26 October 2026. doi:10.
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