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<p>A number of chronic liver illnesses often culminate in liver cirrhosis. It is typically brought on by long-term liver conditions such as viral hepatitis, heavy alcohol use, and metabolic illnesses. The Fas/FasL system is a crucial regulator of the apoptotic process which, alongside inflammation, is a central contributor to the destruction of the liver. Fas and FasL are critical genes involved in regulating fibrosis and inflammation. The aim of this study was to assess the relationship between Fas and FasL gene polymorphisms and the risk of developing liver cirrhosis in a large cohort of patients and controls. Using tetra-primer ARMS-PCR, the Fas-670A &gt; G (rs1800682), Fas-1377G &gt; A (rs2234767), and FasL-844T &gt; C (rs763110) polymorphisms were genotyped in 335 liver cirrhosis patients and 525 healthy controls. The study site was the Gastroenterology Department of Al-Diwaniyah Teaching Hospital. These changes were evaluated with haplotype analysis in order to assess their cumulative effect. The G allele was significantly associated with an increased risk of liver cirrhosis (OR = 1.35, 95% CI 1.12–1.63, <i>p</i> = 0.002) along with the Fas-670 GG genotype (OR = 1.73, 95% CI 1.24–2.41, <i>p</i> = 0.001). Likewise, the C allele (OR = 1.38, 95% CI 1.14–1.67, <i>p</i> = 0.001) and FasL-844 CC genotype (OR = 1.82, 95% CI 1.27–2.61, <i>p</i> = 0.001) also conferred heightened susceptibility. Those with the Fas-670G/-1377G/FasL-844C haplotype had a significantly greater risk compared to those with the Fas-670A/-1377G/FasL-844T haplotype from the haplotype analysis (OR = 2.14, 95% CI 1.58–2.89, <i>p</i> &lt; 0.001). It seems that functional variations of the Fas/FasL system clearly delineate the risk of liver cirrhosis an individual carries, most likely by altering apoptotic pathways involving Fas/FasL system components in liver cirrhosis. These Without a doubt, These polymorphisms may serve as valuable markers for liver cirrhosis risk assessment and understanding its pathogenesis.</p>

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Genetic Determinants of Apoptosis Regulate Liver Cirrhosis Risk: The FAS/FASL Polymorphism Connection in Iraqi Population

  • 期刊论文

  • 发表日期：

    2025年7月14日

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  • Wisam Hindawi Hoidy,
  • Ahmed Ghdhban Al-Ziaydi

摘要

A number of chronic liver illnesses often culminate in liver cirrhosis. It is typically brought on by long-term liver conditions such as viral hepatitis, heavy alcohol use, and metabolic illnesses. The Fas/FasL system is a crucial regulator of the apoptotic process which, alongside inflammation, is a central contributor to the destruction of the liver. Fas and FasL are critical genes involved in regulating fibrosis and inflammation. The aim of this study was to assess the relationship between Fas and FasL gene polymorphisms and the risk of developing liver cirrhosis in a large cohort of patients and controls. Using tetra-primer ARMS-PCR, the Fas-670A > G (rs1800682), Fas-1377G > A (rs2234767), and FasL-844T > C (rs763110) polymorphisms were genotyped in 335 liver cirrhosis patients and 525 healthy controls. The study site was the Gastroenterology Department of Al-Diwaniyah Teaching Hospital. These changes were evaluated with haplotype analysis in order to assess their cumulative effect. The G allele was significantly associated with an increased risk of liver cirrhosis (OR = 1.35, 95% CI 1.12–1.63, p = 0.002) along with the Fas-670 GG genotype (OR = 1.73, 95% CI 1.24–2.41, p = 0.001). Likewise, the C allele (OR = 1.38, 95% CI 1.14–1.67, p = 0.001) and FasL-844 CC genotype (OR = 1.82, 95% CI 1.27–2.61, p = 0.001) also conferred heightened susceptibility. Those with the Fas-670G/-1377G/FasL-844C haplotype had a significantly greater risk compared to those with the Fas-670A/-1377G/FasL-844T haplotype from the haplotype analysis (OR = 2.14, 95% CI 1.58–2.89, p < 0.001). It seems that functional variations of the Fas/FasL system clearly delineate the risk of liver cirrhosis an individual carries, most likely by altering apoptotic pathways involving Fas/FasL system components in liver cirrhosis. These Without a doubt, These polymorphisms may serve as valuable markers for liver cirrhosis risk assessment and understanding its pathogenesis.