Do genetic variants modulate liver injury in patients with diabetes mellitus? – results of a prospective, single center study

Background: Type II diabetes (DMII) and metabolic dysfunction-associated steatotic liver disease (MASLD) are prevalent conditions. MTARC1 p.A165T variant has been identified as a protective factor against MASLD. We assess this polymorphism as a genetic modulator of MASLD in DMII patients, alongside six additional MASLD-linked variants.

Patients and methods: We prospectively enrolled 124 patients with DMII. Liver steatosis and fibrosis were evaluated using controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). The MTARC1 p.A165T, as well as, the HSD17B13, PSD3, MBOAT7, PNPLA3, TM6SF2 and SERPINA1 polymorphisms were genotyped with TaqMan assays. Serum oxidative stress was measured using ELISA and colorimetric tests in 40 patients with different MTARC1 genotypes.

Results: The median LSM was 6.6 kPa (range: 2–75 kPa) and median CAP 294 dB/m (range: 100–400 dB/m). MASLD was found in 52.4% of patients, and cirrhosis (LSM>15 kPa) in 14.5%. CAP correlated significantly with BMI (p<0.01), HbA1c (p=0.02), triglycerides, LDL and total cholesterol (p<0.05). LSM correlated with bilirubin (p=0.01), alkaline phosphatase and GGT (both p<0.01). MTARC1 p.A165T carriers showed 11% lower maximal CAP and 71% lower maximal LSM compared to non-carriers, with higher serum TrxR2 levels (p=0.01). The TM6SF2, MBOAT7, and PSD3 variants significantly (all p<0.05) modulated bilirubin, GOT, GGT, and GPT levels.

Conclusions: The MASLD prevalence in our cohort was consistent with further DMII cohorts. Studied genetic variants influenced liver function tests, and MTARC1 modulated steatosis and fibrosis. MTARC1’s impact on oxidative stress suggests its protective role in liver disease.

Publication History

Article published online:
20 January 2025