Background: Gluconeogenesis and renal glucose excretion in kidneys both play an important role in glucose homeostasis. Sodium-glucose cotransporter (SGLT2), coded by the SLC5A2 gene is responsible for reabsorption up to 99% of the filtered glucose in proximal tubules. SLC5A2 genetic polymorphisms were suggested to influence glucose homeostasis. We investigated if common SLC5A2 rs9934336 polymorphism influences glycemic control and risk for macro or microvascular complications in Slovenian type 2 diabetes (T2D) patients.
Methods: All 181 clinically well characterized T2D patients were genotyped for SLC5A2 rs9934336 G>A polymorphism. Associations with glycemic control and T2D complications were assessed with nonparametric tests and logistic regression.
Results: SLC5A2 rs9934336 was significantly associated with increased fasting blood glucose levels (P<0.001) and HbA1c levels under the dominant genetic model (P=0.030). After adjustment for T2D duration, significantly higher risk for diabetic retinopathy was present in carriers of at least one polymorphic SLC5A2 rs9934336 A allele compared to non-carriers (OR=7.62; 95%CI=1.65-35.28; P=0.009).
Conclusions: Our pilot study suggests an important role of SLC5A2 polymorphisms in the physiologic process of glucose reabsorption in kidneys in T2D patients. This is also the first report on the association between SLC5A2 polymorphism and diabetic retinopathy.
Uvod: Glukoneogeneza i izlučivanje glukoze u bubrezima imaju važnu ulogu u homeostazi glukoze. Natrijum-glukozni kotransporter (SGLT2), kodiran od strane gena SLC5A2, odgovoran je za reapsorpciju do 99% filtrirane glukoze u proksimalnim tubulima. Predloženo je da genetski polimorfizmi SLC5A2 utiču na homeostazu glukoze. Ispitali smo, da li učestali polimorfizam SLC5A2 rs9934336 utiče na glikemičku kontrolu i na rizik za makro i mikrovaskularne komplikacije kod pacijenata iz Slovenije sa dijabetesom tipa 2 (T2D).
Metode: Svih 181 klinički dobro okarakterisanih pacijenata sa T2D je genotipizirano na polimorfizam SLC5A2 rs9934336 G>A. Povezanost sa kontrolom glikemije i komplikacijama T2D ispitivana je neparametrijskim testovima i logističkom regresijom.
Rezultati: SLC5A2 rs9934336 je značajno povezan sa povećanim nivoima glukoze u krvi natašte (P <0,001) i nivoima HbA1c pod dominantnim genetskim modelom (P = 0,030). Nakon uzimanja u obzir trajanje T2D, značajno veci rizik za dijabetičku retinopatiju bio je prisutan kod nosilaca najmanje jednog polimorfnog alela SLC5A2 rs9934336 A u odnosu na pacijente koji nisu nosioci (OR = 7,62; 95% CI = 1,65-35,28; P = 0,009).
Zaključak: Naša pilot-studija ukazuje na važnu ulogu polimorfizama SLC5A2 u fiziološkom procesu reapsorpcije glukoze u bubrezima kod pacijenata sa T2D. Ovo je tako|e prva studija o povezanosti polimorfizma SLC5A2 i dijabetičke retinopatije.
Keywords: SGLT2; SLC5A2; diabetes type 2; genetic polymorphism; retinopathy.
2020 Jasna Klen, Katja Goričar, Vita Dolžan, published by CEON/CEES.