The glucokinase regulator gene (GCKR) rs780094 C>T single nucleotide polymorphism affect diet response in overweight/obese subjects with metabolic-dysfunction associated steatotic liver disease

• Published in: Digestive and liver disease Vol. 56; pp. S49 - S50
• Main Authors: Dileo, E., Rosso, C., Saba, F., Castelnuovo, G., Caviglia, G.P., Armandi, A., Tatoli, M., Perez, NDDC, Guariglia, M., Abate, M.L., Olivero, A., Parasiliti-Caprino, M., Bo, S., Bugianesi, E.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.02.2024
• ISSN: 1590-8658
• DOI: 10.1016/j.dld.2024.01.082

The glucokinase regulator gene (GCKR) rs780094 C>T single nucleotide polymorphism (SNP), involved in the regulation of glucose metabolism, has been associated with obesity and hepatic steatosis in patients with metabolic-dysfunction associated steatotic liver disease (MASLD). We explored its potential impact on diet response in a group of overwight/obese MASLD patients. We analyzed 73 subjects (mean age 51±12y; male, N=50) with MASLD who underwent a calorie-restricted diet for 6 months. At baseline (t0) and after 6-months diet (t6) we collected blood samples and anthropometrical measurements. GCKR rs780094 C>T genotyping was performed by allelic discrimination assay. Hepatic steatosis was determined by controlled attenuation parameter (CAP, Fibroscan®). Overall, 44 (60.3%) patients were obese, 15 (20.5%) had type 2 diabetes and 28 (38.4%) had arterial hypertension. The prevalence of the GCKR rs780094 genotypes was 20.5% (CC), 41.1% (CT) and 38.4% (TT). After 6 months of diet, all patients significantly improved BMI (t0=30.5 kg/m2vs. t6=29.5 kg/m2, p<0.001) and CAP (308 dB/m vs. 274 dB/m, p<0.001). Specifically, a 15% of CAP improvement was observed in 20 subjects (27.4%). CAP and HOMA-IR significantly decreased in patients carrying the GCKR rs780094 TT risk omozygosis compared to those with the CC/CT variants (p=0.045 and p=0.048, respectively). At multivariate logistic regression analysis adjusted for age, gender, weight, HOMA-IR and energy intake, 15% of CAP decrease after diet was associated with GCKR TT genotype (OR=4.04, 95% CI=1.13-14.45, p=0.032). Overweight/obese patients with MASLD carrying the GCKR rs780094 TT genotype are more likely to improve liver steatosis following a calorie-restricted diet. Funded by the University of Turin, g.n. ROSC_RILO_23_01.