Association of Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 Alpha Coding Variants with Hepatocellular Carcinoma Risk in the Moroccan Population: A Case-Control Study

Tanouti, Ikram-Allah; Fellah, Hassan; El Fihry, Raouia; Zerrad, Chaimaa; Abounouh, Karima; Tahiri, Mohamed; Belkouchi, Abdelkader; Badre, Wafaa; Pineau, Pascal; Benjelloun, Soumaya; Ezzikouri, Sayeh

doi:10.31557/APJCP.2023.24.11.3689

Association of Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 Alpha Coding Variants with Hepatocellular Carcinoma Risk in the Moroccan Population: A Case-Control Study

Document Type : Research Articles

Authors

¹ Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco.

² Laboratory of Cellular and Molecular Pathology Infectious Diseases and Systemic Immunology Team, Faculty of Medicine and Pharmacy, University Hassan II of Casablanca, Morocco.

³ CHU Ibn Rochd, Casablanca, Morocco.

⁴ CHU Ibn Sina, Médecine A, Rabat, Morocco.

⁵ Institut Pasteur, Paris Cedex 15 France.

10.31557/APJCP.2023.24.11.3689

Abstract

Background: Hepatocellular carcinoma (HCC) is the most common primary malignancy. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) plays a crucial role in regulating the biogenesis of mitochondria. We aimed to assess the association between PPARGC1A polymorphisms and HCC risk in a Moroccan population. Methods: In this case-control study, 147 patients with HCC and 147 controls without pre-existing liver disease were matched for ethnicity. TaqMan SNP allelic discrimination assays were used for genotyping of PPARGC1A rs8192678 and rs12640088 polymorphisms. Results: The result revealed that individuals with the GA/AA genotypes for rs8192678 had a significantly higher risk of HCC compared to those with the GG genotype (OR=6.68; P<0.0001, and OR=9.78; P<0.0001, respectively). In particular, the A allele of rs8192678 was over-represented in HCC patients compared to controls (40% versus 12%, P<0.0001, respectively). With respect to PPARGC1A rs12640088 variant, two genetic models (codominant and dominant) were tested to explore any potential variations in the distribution of SNP A>C among HCC cases and control subjects group. Overall, no significant association between rs12640088 and HCC was found (P>0.05). Interestingly, a significantly higher level of aspartate aminotransferase was observed in HCC patients with GG-GA genotypes (280 IU/L) compared to those with GG genotype (164 IU/L) at rs8192678 (P=0.0019). Conclusion: Our results suggest that the PPARGC1A rs8192678 polymorphism is associated with an increased risk of HCC in Moroccan population and may serve as a prognostic marker for liver cancer.

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