Serum Gc system in liver cirrhosis and hepatoma

Theodoropoulos, George; Rigatos, G.; Babionitakis, A.; Archimandritis, Athanasios; Fertakis, A; Melissinos, K.

doi:10.1007/bf00287016

Cited by 8 publications

(6 citation statements)

References 13 publications

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“…Initial studies found no association between the heterozygous α 1 AT phenotypes and LDs (2‐5). However, several later studies have suggested that such association may in fact exist (6‐12).…”

Section: Discussionmentioning

confidence: 99%

“…Homozygous PiZZ alpha‐1 antitrypsin deficiency (α 1 ATD) is a well‐known cause of liver disease (LD) in children and adults (1). However, the role of the heterozygous PiZ state of α 1 ATD in the pathogenesis of chronic LD is still a matter of controversy (2‐4). Although initial reports found no association between the PiZ carrier state and LD (2,4,5), recent studies have suggested that the presence of PiZ may explain some cases of LD of unknown etiology including cryptogenic cirrhosis (6‐12).…”

Section: Introductionmentioning

confidence: 99%

“…However, the role of the heterozygous PiZ state of α 1 ATD in the pathogenesis of chronic LD is still a matter of controversy (2‐4). Although initial reports found no association between the PiZ carrier state and LD (2,4,5), recent studies have suggested that the presence of PiZ may explain some cases of LD of unknown etiology including cryptogenic cirrhosis (6‐12). Unfortunately, most of these studies were conducted before the discovery of the hepatitis C virus (HCV) and before the association between nonalcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis was established.…”

Section: Introductionmentioning

confidence: 99%

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Does the Heterozygous State of Alpha‐1 Antitrypsin Deficiency Have a Role in Chronic Liver Diseases? Interim Results of a Large Case‐Control Study

Regev

Guaqueta

Molina

et al. 2006

J. pediatr. gastroenterol. nutr.

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We found no association between the heterozygous PiZ state of alpha1ATD and the presence of chronic LD in-general or the presence of cryptogenic cirrhosis. In contrast, patients with decompensated LD of any etiology had a significantly higher prevalence of PiMZ compared with patients with compensated LD. Furthermore, in patients with chronic LD due to HCV or NAFLD there was a significant association between the PiMZ heterozygous state and increased severity of LD and the need for liver transplantation. These interim results suggest that the PiMZ alpha1ATD heterozygous state may have a role in worsening LD due to HCV or NAFLD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Does the Heterozygous State of Alpha‐1 Antitrypsin Deficiency Have a Role in Chronic Liver Diseases? Interim Results of a Large Case‐Control Study

Regev

Guaqueta

Molina

et al. 2006

J. pediatr. gastroenterol. nutr.

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“…Individual susceptibilities to diseases can also be correlated to genetic markers not coded by the HLA system; Theodoropoulos et al (1977), for example, have found that the Gc2 gene coding for the corresponding phenotype of the Ge serum glycoprotein was a risk factor for PLC without cirrhosis; various patterns such as serum deficiency, periodicacid-stain-positive and diastase-resistant globules in hepatocytes of another serum protein also produced by the liver (the of -antitrypsin (al-AT)) have been found by some authors to be associated with diseases such as chronic obstructive lung Acceptedl 16 October 1980 disease, pulmonary emphysema, juvenile and adult liver cirrhosis and PLC. al-AT, a major serum protease inhibitor, can exist under many genetically coded forms which can be identified by electrophoresis techniques in relation to differences of electric charge.…”

mentioning

confidence: 99%

M2 alpha-1-antitrypsin phenotype and primary liver cancer

Sizaret¹,

Clerc²,

Estève³

et al. 1981

Br J Cancer

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“…(4,5) While the risk of chronic liver disease in patients homozygous for the SERPINA1 Z allele has been well studied, (6)(7)(8)(9)(10) the risk of liver disease in heterozygous carriers of the SERPINA1 Z allele (Pi*Z) remains under investigation. Although initial reports found no association between Z allele heterozygotes and the risk of liver disease, (11)(12)(13)(14) other case-control studies have shown an effect of the Z allele on cystic fibrosis-related liver disease, (15) alcoholic and nonalcoholic fatty liver disease, (16)(17)(18) portal hypertension, (19) and liver stiffness and elevated serum transaminases. (20) A limitation of these studies is that many have been carried out in relatively small sample sizes with a limited number of subjects with the Pi*Z genotype.…”

mentioning

confidence: 92%

Heterozygosity of the Alpha 1‐Antitrypsin Pi*Z Allele and Risk of Liver Disease

et al. 2021

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The serpin family A member 1 (SERPINA1) Z allele is present in approximately one in 25 individuals of European ancestry. Z allele homozygosity (Pi*ZZ) is the most common cause of alpha 1‐antitrypsin deficiency and is a proven risk factor for cirrhosis. We examined whether heterozygous Z allele (Pi*Z) carriers in United Kingdom (UK) Biobank, a population‐based cohort, are at increased risk of liver disease. We replicated findings in Massachusetts General Brigham Biobank, a hospital‐based cohort. We also examined variants associated with liver disease and assessed for gene–gene and gene–environment interactions. In UK Biobank, we identified 1,493 cases of cirrhosis, 12,603 Z allele heterozygotes, and 129 Z allele homozygotes among 312,671 unrelated white British participants. Heterozygous carriage of the Z allele was associated with cirrhosis compared to noncarriage (odds ratio [OR], 1.53; P = 1.1×10−04); homozygosity of the Z allele also increased the risk of cirrhosis (OR, 11.8; P = 1.8 × 10−09). The OR for cirrhosis of the Z allele was comparable to that of well‐established genetic variants, including patatin‐like phospholipase domain containing 3 (PNPLA3) I148M (OR, 1.48; P = 1.1 × 10−22) and transmembrane 6 superfamily member 2 (TM6SF2) E167K (OR, 1.34; P = 2.6 × 10−06). In heterozygotes compared to noncarriers, the Z allele was associated with higher alanine aminotransferase (ALT; P = = 4.6 × 10−46), aspartate aminotransferase (AST; P = 2.2 × 10−27), alkaline phosphatase (P = 3.3 × 10−43), gamma‐glutamyltransferase (P = 1.2 × 10−05), and total bilirubin (P = 6.4 × 10−06); Z allele homozygotes had even greater elevations in liver biochemistries. Body mass index (BMI) amplified the association of the Z allele for ALT (P interaction = 0.021) and AST (P interaction = 0.0040), suggesting a gene–environment interaction. Finally, we demonstrated genetic interactions between variants in PNPLA3, TM6SF2, and hydroxysteroid 17‐beta dehydrogenase 13 (HSD17B13); there was no evidence of epistasis between the Z allele and these variants. Conclusion: SERPINA1 Z allele heterozygosity is an important risk factor for liver disease; this risk is amplified by increasing BMI.

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Serum Gc system in liver cirrhosis and hepatoma

Cited by 8 publications

References 13 publications

Does the Heterozygous State of Alpha‐1 Antitrypsin Deficiency Have a Role in Chronic Liver Diseases? Interim Results of a Large Case‐Control Study

Does the Heterozygous State of Alpha‐1 Antitrypsin Deficiency Have a Role in Chronic Liver Diseases? Interim Results of a Large Case‐Control Study

M2 alpha-1-antitrypsin phenotype and primary liver cancer

Heterozygosity of the Alpha 1‐Antitrypsin Pi*Z Allele and Risk of Liver Disease

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