A preliminary investigation of the association between haptoglobin polymorphism, serum ferritin concentration and fatty liver disease

Nakagawa, Takehiro; Muramoto, Yosuke; Hori, Masaharu; Mihara, Shuichi; Marubayashi, Toru; Nakagawa, Kazuko

doi:10.1016/j.cca.2008.08.004

Cited by 14 publications

(10 citation statements)

References 26 publications

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“…The HP2 2 genotype was found to be positively associated with carotid IMT and the HP2 allele was associated with decreased serum triglyceride concentrations. We identified an association with T2DM in EAs that has not been reported previously [39-41]. Further studies are needed to extend and replicate these relationships.…”

Section: Discussionsupporting

confidence: 49%

Genetic analysis of haptoglobin polymorphisms with cardiovascular disease and type 2 diabetes in the diabetes heart study

Adams

Cox

Freedman

et al. 2013

Cardiovasc Diabetol

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BackgroundHaptoglobin (HP) is an acute phase protein that binds to freely circulating hemoglobin. HP exists as two distinct forms, HP1 and HP2. The longer HP2 form has been associated with cardiovascular (CVD) events and mortality in individuals with type 2 diabetes (T2DM).MethodsThis study examined the association of HP genotypes with subclinical CVD, T2DM risk, and associated risk factors in a T2DM-enriched sample. Haptoglobin genotypes were determined in 1208 European Americans (EA) from 473 Diabetes Heart Study (DHS) families via PCR. Three promoter SNPs (rs5467, rs5470, and rs5471) were also genotyped.ResultsAnalyses revealed association between HP2-2 duplication and increased carotid intima-media thickness (IMT; p = 0.001). No association between HP and measures of calcified arterial plaque were observed, but the HP polymorphism was associated with triglyceride concentrations (p = 0.005) and CVD mortality (p = 0.04). We found that the HP2-2 genotype was associated with increased T2DM risk with an odds ratio (OR) of 1.49 (95% CI 1.18-1.86, p = 6.59x10-4). Promoter SNPs were not associated with any traits.ConclusionsThis study suggests association between the HP duplication and IMT, triglycerides, CVD mortality, and T2DM in an EA population enriched for T2DM. Lack of association with atherosclerotic calcified plaque likely reflect differences in the pathogenesis of these CVD phenotypes. HP variation may contribute to the heritable risk for CVD complications in T2DM.

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Section: Discussionsupporting

confidence: 49%

Genetic analysis of haptoglobin polymorphisms with cardiovascular disease and type 2 diabetes in the diabetes heart study

Adams

Cox

Freedman

et al. 2013

Cardiovasc Diabetol

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“…Importantly, haptoglobin acts mainly as an antioxidant, binding to free hemoglobin and thereby inhibiting the hemoglobin-induced oxidative damage to tissues. Because both inflammation and oxidative injury are thought to contribute to the development of NAFLD, haptoglobin has the potential to be a determinant of NAFLD risk and can modulate the risk linked to free hemoglobin levels [33].…”

Section: Discussionmentioning

confidence: 99%

Serum proteomic analysis revealed diagnostic value of hemoglobin for nonalcoholic fatty liver disease

et al. 2012

Journal of Hepatology

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“…A number of previous studies have examined the frequent presence of hyperferritinemia with or without increased hepatic iron storage in patients with NAFLD 31‐43. It was suggested that increased hepatic iron stores, possibly via mutations in HFE , the hemochromatosis gene, may lead to NASH and advanced fibrosis in NAFLD via increased oxidative stress 53.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is plausible that SF may reflect increased disease severity in NAFLD either because of increased ongoing hepatic or systemic inflammation or increased body iron stores or a combination of these factors. Previous studies examining the relationship between SF level and histologic severity in NAFLD have found conflicting results, with some investigators reporting that SF levels are associated with increased histologic severity and the presence of NASH, whereas others have not 31‐43. We have previously described that patients with NASH have significantly higher median SF levels, compared to those with NAFLD 44.…”

mentioning

confidence: 83%

Serum Ferritin Is An Independent Predictor of Histologic Severity and Advanced Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

Kowdley¹,

Belt²,

Wilson³

et al. 2012

Hepatology

472

393

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Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD), due to systemic inflammation, increased iron stores or both. The aim of this study was to examine the relationship between elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory and anthropometric data were analyzed in 628 adult patients with NAFLD (age≥18 years) with biopsy-proven NAFLD and a serum ferritin measurement within six months of their liver biopsy. A threshold SF>1.5XULN (i.e. >300 ng/ml in women and >450 ng/ml in men) was significantly associated with male sex, elevated serum ALT, AST, iron, transferrin-iron saturation, iron stain grade and decreased platelets (p<0.01). Histologic features of NAFLD were more severe among patients with SF>1.5XULN including steatosis, fibrosis, hepatocellular ballooning and diagnosis of NASH (p<0.026). On multiple regression analysis, SF>1.5XULN was independently associated with advanced hepatic fibrosis (OR, 1.66, 95% CI, 1.05-2.62, p=0.028) and increased NAFLD Activity Score (NAS) (OR, 1.99, 95% CI, 1.06-3.75, p=0.033). Conclusions A SF >1.5XULN is associated with hepatic iron deposition, a diagnosis of NASH, and worsened histologic activity, and is an independent predictor of advanced hepatic fibrosis among patients with NAFLD. Furthermore, elevated SF is independently associated with higher NAS even among patients without hepatic iron deposition. We conclude that serum ferritin is useful to identify NAFLD patients at risk for NASH and advanced fibrosis.

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A preliminary investigation of the association between haptoglobin polymorphism, serum ferritin concentration and fatty liver disease

Cited by 14 publications

References 26 publications

Genetic analysis of haptoglobin polymorphisms with cardiovascular disease and type 2 diabetes in the diabetes heart study

Genetic analysis of haptoglobin polymorphisms with cardiovascular disease and type 2 diabetes in the diabetes heart study

Serum proteomic analysis revealed diagnostic value of hemoglobin for nonalcoholic fatty liver disease

Serum Ferritin Is An Independent Predictor of Histologic Severity and Advanced Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

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