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Purpose: The correlation between patatin-like phospholipase domain-containing protein 3 () rs738409 polymorphism and hepatocellular carcinoma was investigated by several pilot studies, but the results of these studies were controversial. Therefore, we performed this study to better assess the relationship between rs738409 polymorphism and the likelihood of hepatocellular carcinoma.
Methods: Eligible studies were searched in PubMed, Medline, EMBASE, and Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relationship between rs738409 polymorphism and hepatocellular carcinoma.
Results: A total of 17 studies with 10,330 participants were analyzed. A significant association with the likelihood of hepatocellular carcinoma was detected for the rs738409 polymorphism in dominant ( = 0.0001; OR 0.66; 95% CI 0.53, 0.82), recessive ( < 0.0001; OR 2.32; 95% CI 1.76, 3.06) and allele ( < 0.0001; OR 0.64; 95% CI 0.53, 0.77) comparisons. Further subgroup analyses revealed that the rs738409 polymorphism was significantly associated with the likelihood of hepatocellular carcinoma in Caucasians (dominant model: < 0.0001, OR 0.57, 95% CI 0.45, 0.71; recessive model: < 0.0001, OR 2.74, 95% CI 2.02, 3.71; allele model: < 0.0001, OR 0.56, 95% CI 0.46, 0.67). However, no positive results were detected in Asians.
Conclusions: Our findings indicated that the rs738409 polymorphism may serve as a potential biological marker of hepatocellular carcinoma in Caucasians.
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http://dx.doi.org/10.1177/1724600818812471 | DOI Listing |
Clin Exp Hepatol
June 2025
National Liver Institute, Menofia University, Egypt.
Aim Of The Study: One of the main causes of cancer-related death worldwide is hepatocellular carcinoma (HCC), which is significantly common in Egypt because of the high prevalence of hepatitis C virus (HCV) infection. The development of HCC has been linked to genetic variations in the (rs58542926) and (rs738409) genes. The aim of this study was to assess PNPLA3 and TM6SF2 genetic variants as risk factors for HCC in Egyptian patients with chronic HCV disease.
View Article and Find Full Text PDFNucleic Acid Ther
September 2025
Translational Safety & Risk Sciences, Amgen, Inc, Thousand Oaks, California, USA.
The single nucleotide polymorphism, rs738409, is the strongest known genetic risk factor for metabolic dysfunction-associated steatotic liver disease; thus, targeting the minor allele with a GalNAc-conjugated siRNA is an attractive strategy to treat patients carrying the genetic variant. To enable translational safety assessment of a GalNAc-conjugated siRNA that specifically targets the rs738409 sequence of , a transgenic human knock-in mouse (hu) was utilized. This model showed no significant genotype-related phenotypic differences to wild-type mice in a phenotype characterization study when maintained on standard rodent chow.
View Article and Find Full Text PDFCurr Issues Mol Biol
August 2025
Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 16094, Mongolia.
Background: This study aimed to determine the association between rs738409, rs2896019, and rs9939609, rs17817449 single-nucleotide polymorphisms and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in Mongolian individuals.
Methods: 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 , and rs9939609 in ).
Cureus
July 2025
General Medicine, Shri B. M. Patil Medical College Hospital and Research Center, Bharatiya Lingayat Development Educational Association (BLDEA) (Deemed to be University), Vijayapura, IND.
Background: Alcoholic liver disease (ALD) is a significant cause of liver-related morbidity and mortality worldwide. The role of genetic factors, particularly the patatin-like phospholipase domain-containing 3 (PNPLA3) gene, in the progression of ALD remains underexplored in the Indian population. This study aims to investigate the molecular characterization of the PNPLA3 gene polymorphism in individuals with ALD in India.
View Article and Find Full Text PDFInt J Mol Sci
August 2025
Department of Immunogenetics, Northeast Biomedical Research Centre, Mexican Social Security Institute, Monterrey 64320, NL, Mexico.
Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer with an increasing incidence worldwide. Single nucleotide polymorphisms (SNPs) may influence disease risk and serve as predictive markers. This study aimed to evaluate the association of (rs738409 and rs2294918), (rs780094), (rs641738), (rs2228603), and (rs58542926) SNPs with the risk of developing HCC in a Mexican population.
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