Genetic Risk of MASLD in Mongolians: Role of PNPLA3 and FTO SNPs

This study aimed to determine the association between PNPLA3 rs738409, rs2896019, and FTO rs9939609, rs17817449 single-nucleotide polymorphisms and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in Mongolian individuals.

We conducted a case-control study, enrolling 100 MASLD patients and 50 subjects without MASLD. We used the PCR-RFLP technique on three genotype SNPs (rs738409, rs2896019 in PNPLA3, and rs9939609 in FTO). We analyzed liver function and lipid metabolism parameters in the peripheral blood of study participants. A p-value below 0.05 was considered a statistically significant result.

This study, which included 150 participants aged 23 to 75, had a mean age of 46.73 ± 11.45 years, with 40% of participants being male (60 individuals). We observed the rs738409 (G), rs2896019 (G), and rs9939609 (A) alleles at a statistically significantly enhanced frequency in the case group (32.5%, 33%, and 21%) compared to the control group (19%, 25%, and 19%), indicating an increased risk of MASLD. The FTO rs17817449 SNP did not show a significant difference between groups. PNPLA3 rs738409 GC/GG genotype (OR = 2.39, p = 0.019) and FTO rs9939609 AT/AA (OR = 2.55, p = 0.025) genotype showed a significant association with MASLD. In the evaluation of the FTO rs9939609, rs17817449, and PNPLA3 rs738409, rs2896019 single-nucleotide polymorphisms among the research individuals, 18.7% had no SNPs, 15.3% had one SNP, 29.3% had two SNPs, 25.3% had three SNPs, and 11.3% had four SNPs. The risk of MASLD increased significantly for individuals having four SNPs (OR = 4.23, p = 0.007).

We found that PNPLA3 rs738409 GC/GG genotype and FTO rs9939609 AT/AA genotype are strongly associated with an increased risk of MASLD. Notably, individuals with a higher rate of SNP number, had a significantly higher risk of MASLD.