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Unraveling the Genetic Determinants of SGLT2 Inhibitor Response in Type 2 Diabetes: A Pharmacogenetic Study Using UK Biobank Data

Terrmin

HT25

Beskrivning

Background
Have you ever wondered why the same medicine can work differently for different people? In type 2 diabetes, SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin, and canagliflozin) can lower blood sugar and, by doing so, protect the heart and kidneys. However, not everyone responds in the same way—some patients benefit strongly, while others experience side effects or less improvement. Certain genetic differences may influence these variable responses.
Aim
This project aims to identify which genetic variations (SNPs) and combined genetic scores (polygenic risk scores, PRS) predict how well patients respond to SGLT2 inhibitors. We will investigate whether genetic markers can forecast immediate improvements in blood sugar control, longer-term outcomes like heart and kidney health, or whether some genetic variants may be linked to a higher risk of side effects. By uncovering these genetic factors, we hope to move closer to personalized diabetes treatments that are safer and more effective.
Methods
• Data Source: We will use the UK Biobank, which contains detailed health and genetic records on about 500,000 people.
• Study Population: Participants with type 2 diabetes who have been prescribed SGLT2 inhibitors.
• Genetic Analysis: We will focus on specific genes (e.g., SLC5A2, KCNJ11, TCF7L2, CYP3A4, UGT1A9) to see how certain variants might affect the way SGLT2 inhibitors work. We will also calculate genetic risk scores that combine multiple genetic signals.

Outcomes: We will examine short- and long-term responses (e.g., blood sugar levels, adverse events such as urinary tract infections or ketoacidosis). Statistical models will be used to determine which genetic patterns are linked to better or worse outcomes.

Projektets upplägg kräver studentens närvaro på plats måndag till fredag under hela arbetsdagen. Detta för att säkerställa full delaktighet i det dagliga arbetet och möjliggöra ett nära samarbete med projektgruppen.

Huvudområde

Farmaceutisk vetenskap

Ämne

Farmakologi

Typ

Registerstudie

Företag

Läkemedelsverket

Ort/Plats

Uppsala

Handledarens namn

Jessica Mwinyi och Linda Wahlström

Handledarens e-post

jessica.mwinyi@lakemedelsverket.se, linda.wahlstrom@lakemedelsverket.se

Institution

Institutionen för farmaceutisk biovetenskap

Program

Apotekarprogrammet

Kurs

Fördjupningsprojekt i farmaceutisk farmakologi 30 hp - 3FF293

Omfattning/hp

30hp

Hur många studenter kan antagas för detta projekt?

1

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