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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).
CONCLUSIONS: 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.
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).
CONCLUSIONS: 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.
摘要：
背景：肝细胞癌（HCC）是最常见的原发性恶性肿瘤。过氧化物酶体增殖物激活受体γ-共激活因子1α(PPARGC1A)在调节线粒体的生物发生中起着至关重要的作用。我们旨在评估摩洛哥人群中PPARGC1A多态性与HCC风险之间的关联。
方法：在本病例对照研究中，147例HCC患者和147例对照没有预先存在的肝病进行种族匹配。TaqManSNP等位基因鉴别测定用于PPARGC1Ars8192678和rs12640088多态性的基因分型。
结果：结果显示，与GG基因型相比，rs8192678具有GA/AA基因型的个体患HCC的风险明显更高（OR=6.68；P<0.0001，和OR=9.78；P<0.0001，分别）。特别是,与对照组相比，rs8192678的A等位基因在HCC患者中过度表达(40%对12%，P分别<0.0001)。关于PPARGC1Ars12640088变体，测试了两个遗传模型(共显性和显性),以探索HCC病例和对照组中SNPA>C分布的任何潜在变化。总的来说,rs12640088与HCC无显著相关性(P>0.05)。有趣的是,在rs8192678(P=0.0019),与GG基因型(164IU/L)的HCC患者相比,GG-GA基因型(280IU/L)的患者的天冬氨酸转氨酶水平显著较高.
结论：我们的结果表明，PPARGC1Ars8192678多态性与摩洛哥人群的HCC风险增加相关，并可能作为肝癌的预后标志物。
方法：在本病例对照研究中，147例HCC患者和147例对照没有预先存在的肝病进行种族匹配。TaqManSNP等位基因鉴别测定用于PPARGC1Ars8192678和rs12640088多态性的基因分型。
结果：结果显示，与GG基因型相比，rs8192678具有GA/AA基因型的个体患HCC的风险明显更高（OR=6.68；P<0.0001，和OR=9.78；P<0.0001，分别）。特别是,与对照组相比，rs8192678的A等位基因在HCC患者中过度表达(40%对12%，P分别<0.0001)。关于PPARGC1Ars12640088变体，测试了两个遗传模型(共显性和显性),以探索HCC病例和对照组中SNPA>C分布的任何潜在变化。总的来说,rs12640088与HCC无显著相关性(P>0.05)。有趣的是,在rs8192678(P=0.0019),与GG基因型(164IU/L)的HCC患者相比,GG-GA基因型(280IU/L)的患者的天冬氨酸转氨酶水平显著较高.
结论：我们的结果表明，PPARGC1Ars8192678多态性与摩洛哥人群的HCC风险增加相关，并可能作为肝癌的预后标志物。
