The patatin-like phospholipase domain containing 3 (PNPLA3) gene (viz. its I148M variant) is one of the key players in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We have identified a novel insertion/deletion variant of 1114 bp, localized in the second intron of the PNPLA3 gene, which corresponds to the 3' terminal sequence of the long-interspersed element (LINE-1). DNA analysis of 122 NAFLD patients and 167 control subjects as well as RNA analysis of 19 liver biopsies revealed that the novel variant is very common (frequency = 0.41), fully linked to the clinically important I148M variant, and clinically silent. Although the LINE-1 insertion does not seem to have any biological effect, it can impede genotyping of the I148M variant. If insertion prevents the attachment of the diagnostic primer, then the non-insertion allele will be selectively amplified; and thus the frequency of the 148M "risk" allele will be significantly overestimated due to the complete linkage of the LINE-1 insertion and the 148I allele of the PNPLA3 gene. Therefore, our findings underline the importance of careful design and consistent documentation of the methodology, including primer sequences. Critical revisions of the results of some studies that have already been reported may therefore be needed.

• MeSH
• Acyltransferases genetics   MeSH
• Alleles MeSH
• Long Interspersed Nucleotide Elements genetics   MeSH
• Phospholipases A2, Calcium-Independent genetics   MeSH
• Genetic Predisposition to Disease genetics   MeSH
• Genotype MeSH
• Liver pathology   MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Humans MeSH
• Non-alcoholic Fatty Liver Disease genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Acyltransferases MeSH
• adiponutrin, human MeSH Browser
• Phospholipases A2, Calcium-Independent MeSH

Nutritional factors which exhibit antioxidant properties, such as those contained in green plants, may be protective against cancer. Chlorophyll and other tetrapyrrolic compounds which are structurally related to heme and bilirubin (a bile pigment with antioxidant activity) are among those molecules which are purportedly responsible for these effects. Therefore, the aim of our study was to assess both the antiproliferative and antioxidative effects of chlorophylls (chlorophyll a/b, chlorophyllin, and pheophytin a) in experimental pancreatic cancer. Chlorophylls have been shown to produce antiproliferative effects in pancreatic cancer cell lines (PaTu-8902, MiaPaCa-2, and BxPC-3) in a dose-dependent manner (10-125 μmol/L). Chlorophylls also have been observed to inhibit heme oxygenase (HMOX) mRNA expression and HMOX enzymatic activity, substantially affecting the redox environment of pancreatic cancer cells, including the production of mitochondrial/whole-cell reactive oxygen species, and alter the ratio of reduced-to-oxidized glutathione. Importantly, chlorophyll-mediated suppression of pancreatic cancer cell viability has been replicated in in vivo experiments, where the administration of chlorophyll a resulted in the significant reduction of pancreatic tumor size in xenotransplanted nude mice. In conclusion, this data suggests that chlorophyll-mediated changes on the redox status of pancreatic cancer cells might be responsible for their antiproliferative and anticancer effects and thus contribute to the decreased incidence of cancer among individuals who consume green vegetables.

• MeSH
• Antioxidants metabolism   MeSH
• Chlorophyll pharmacology   MeSH
• Extracellular Signal-Regulated MAP Kinases metabolism   MeSH
• Pheophytins metabolism   MeSH
• Glutathione metabolism   MeSH
• Glutathione Disulfide metabolism   MeSH
• Heme Oxygenase (Decyclizing) metabolism   MeSH
• Real-Time Polymerase Chain Reaction MeSH
• Humans MeSH
• Mitochondria drug effects   metabolism   MeSH
• Cell Line, Tumor MeSH
• Pancreatic Neoplasms metabolism   MeSH
• Oxidation-Reduction drug effects   MeSH
• Hydrogen Peroxide metabolism   MeSH
• Antineoplastic Agents pharmacology   MeSH
• Superoxides metabolism   MeSH
• Synechocystis chemistry   MeSH
• Cell Survival drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antioxidants MeSH
• Chlorophyll MeSH
• Extracellular Signal-Regulated MAP Kinases MeSH
• Pheophytins MeSH
• Glutathione MeSH
• Glutathione Disulfide MeSH
• Heme Oxygenase (Decyclizing) MeSH
• Hydrogen Peroxide MeSH
• pheophytin a MeSH Browser
• Antineoplastic Agents MeSH
• Superoxides MeSH