Biomedical subjects

Paola Dongiovanni

Publications and source records attributed to Paola Dongiovanni.

4 recordsLinked to original sources

PubMed2006

Alpha 1-antitrypsin mutations in NAFLD: high prevalence and association with altered iron metabolism but not with liver damage.

Hyperferritinemia, a common feature of nonalcoholic fatty liver disease (NAFLD), has been associated with steatohepatitis and fibrosis. Heterozygosity for alpha 1-antitrypsin (AAT) mutations is a cofactor of liver damage, and AAT influences inflammation and iron metabolism. This study evaluated the prevalence of the common AAT PiS/PiZ mutants in 353 patients with NAFLD, 195 of whom had hyperferritinemia, versus 114 matched controls and their influence on iron metabolism and the severity of liver damage in the 212 patients submitted to biopsy. PiS and PiZ alleles were searched for by restriction analysis. Thirty-eight patients (10.8%) carried non-MM genotypes versus 4/114 (3.5%) controls (P = .02). Patients carrying AAT mutations had higher ferritin (573 [454-966] vs. 348 [201-648]; P = .001) with similar transferrin saturation. The difference was more evident in males (P < .0001) and significant in patients not carrying HFE genotypes associated with iron overload (P = .015). The prevalence of non-MM genotypes was higher in patients with hyperferritinemia than in those without (28/195, 14% vs. 10/158, 6%, P = .016), and AAT mutations were associated with higher prevalence of sinusoidal siderosis (17/27, 63% vs. 70/180, 39%; P = .02), and sinusoidal/total iron score (46.3 +/- 38% vs. 25.1 +/- 35%, P = .01). Although ferritin was independently associated with fibrosis (P = .047), AAT mutations favoring sinusoidal iron deposition did not affect liver damage. In conclusion, AAT mutations are associated with hyperferritinemia and sinusoidal iron accumulation, but not with more severe liver damage in NAFLD.

Alleles↗

PubMed2005

TNFalpha genotype affects TNFalpha release, insulin sensitivity and the severity of liver disease in HCV chronic hepatitis.

BACKGROUND/AIMS: TNFalpha induces insulin resistance and promoter polymorphisms of TNFalpha gene affect the release of this cytokine, implicated in the pathogenesis of HCV-related diabetes and fatty liver. The aim was to define whether in patients with HCV chronic hepatitis TNFalpha genotype influences TNFalpha activity, insulin resistance, and the severity of the disease. METHODS: 186 patients, 65% with steatosis, 17% with diabetes. TNFalpha and sTNFR2 were determined by ELISA, insulin resistance by HOMA-R index and TNFalpha -238, -308, and -863 polymorphisms by restriction analysis. RESULTS: TNFalpha, sTNFR2, and insulin resistance were higher in patients than in 89 controls. TNFalpha pathway activity was correlated with LDL cholesterol, steatosis, and insulin resistance, which, in turn, was correlated with the severity of liver damage. Patients subdivided according to TNFalpha genotype significantly differed for TNFalpha release, insulin sensitivity and the prevalence of cirrhosis. The -308 and -238 TNFalpha polymorphisms, characterized by increased promoter activity, were associated with higher TNFalpha activity, insulin resistance and severity of the disease, whereas the -863 polymorphism, characterized by reduced promoter activity, with lower TNFalpha activity, and higher insulin sensitivity. CONCLUSIONS: TNFalpha genotype modulates the activity of the TNFalpha pathway, influences insulin sensitivity and the severity of HCV chronic hepatitis.

Adult↗

PubMed2004

TNFalpha promoter polymorphisms.

Polymorphisms in the promoter of the tumor necrosis factor alpha (TNFalpha) gene have been reported to affect the transcription rate and the release of this cytokine. Among the best studied, the -238 and -308 polymorphisms have been associated with an increased transcriptional activity and TNFalpha release, whereas the -863 polymorphism have been associated with a reduced transcriptional activity. A growing body of evidence indicates that these polymorphisms may affect susceptibility to different diseases. Here we describe a method to detect the -238, -308, and -863 TNFalpha polymorphisms by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Briefly, DNA is amplified by PCR using mutagenic primers containing a single base-pair mismatch adjacent to the polymorphic site to introduce a restriction site into the wild-type nucleotide sequences after amplification. The PCR products are then digested with specific restriction enzymes and analyzed by agarose gel electrophoresis.

Alleles↗

PubMed2002

Tumor necrosis factor alpha promoter polymorphisms and insulin resistance in nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease, which can range from fatty liver alone to nonalcoholic steatohepatitis and cirrhosis, is related to insulin resistance. Tumor necrosis factor alpha (TNF-alpha) may induce insulin resistance, and polymorphisms of its promoter have been associated with an increased release of this cytokine. We analyzed (1) the prevalence of insulin resistance, (2) the prevalence of the 238 and 308 TNF-alpha polymorphisms, and (3) the relationship among TNF-alpha polymorphisms, insulin resistance, and the occurrence of steatohepatitis in 99 patients with nonalcoholic fatty liver diagnosed by ultrasonography and confirmed by histologic analysis in the 53 who underwent biopsy. METHODS: Insulin resistance was evaluated by the homeostatic metabolic assessment insulin resistance indices and TNF-alpha polymorphisms by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Insulin resistance was detected in almost all of the patients and was more severe in those with steatohepatitis. The prevalence of the 238, but not of the 308, TNF-alpha polymorphism was higher in subjects with nonalcoholic fatty liver than in controls (31% vs. 15%; P < 0.0001), and patients positive for TNF-alpha polymorphisms had higher insulin resistance indices, a higher prevalence of impaired glucose tolerance, and a lower number of associated risk factors for steatosis. CONCLUSIONS: TNF-alpha polymorphisms could represent a susceptibility genotype for insulin resistance, nonalcoholic fatty liver, and steatohepatitis.

Adult↗