Relationship of serum fetuin-A levels with coronary atherosclerotic burden and NAFLD in patients undergoing elective coronary angiography.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) patients are prone to coronary artery disease (CAD). Fetuin-A inhibits arterial calcification, induces insulin resistance, and is increased in NAFLD. Data on fetuin-A levels in CAD are conflicting. We tried to ascertain whether NAFLD and CAD are associated and if fetuin-A predicts CAD and/or NAFLD. METHODS: CAD was diagnosed by ≥50% stenosis in coronary arteries and NAFLD by ultrasound imaging in the absence of any other liver disease. Seventy patients who underwent elective coronarography at our hospital were recruited in this cross-sectional study. Twenty-four patients had no CAD (9 with and 15 without NAFLD) and 46 had CAD (20 with and 26 without NAFLD). Standard anthropometric indices and metabolic parameters were recorded. Fetuin-A was determined by enzyme-linked immunosorbent assay (ELISA). Visceral fat thickness and visceral/subcutaneous fat ratio were assessed by ultrasonography. RESULTS: NAFLD was not associated with CAD, probably owing to the limited series. Fetuin-A was significantly lower, whereas visceral fat thickness and visceral/subcutaneous fat ratio were higher in patients with CAD versus those without CAD. Younger age and higher body mass index (BMI), waist circumference, triglycerides, fasting glucose, homeostasis model assessment, spleen area, subcutaneous fat thickness, and prevalence of metabolic derangements were associated with NAFLD. At multivariate analysis, elevated fetuin-A levels were an independent negative predictor of CAD [odds ratio (OR)=0.995, P=0.049]. Fetuin-A was an independent predictor of NAFLD (OR=1.005, P=0.036) in the model including BMI. CONCLUSIONS: This prospective cross-sectional study demonstrates high fetuin-A levels to be independently associated with NAFLD and a lower risk of coronarographically diagnosed CAD.

ABCB4 and ABCB11 mutations in intrahepatic cholestasis of pregnancy in an Italian population.

BACKGROUND: Genetic alterations in the ATP-binding cassette subfamily B member 4 (ABCB4) and ATP-binding cassette subfamily B member 11 (ABCB11) have been associated to the onset of intrahepatic cholestasis of pregnancy (ICP) in predisposed women. AIMS: To identify new and/or frequent ABCB4 and ABCB11 genes variants in a cohort of Italian patients with ICP and to evaluate the possible pathogenetic role for the novel mutations identified. METHODS: DNA of 33 unrelated Italian women with obstetric cholestasis were screened for mutations in the entire coding sequence of ABCB4 and ABCB11 genes. Polymerase chain reaction and automated sequencing was performed on the 27 coding exons of both genes. RESULTS: Genotyping revealed 11 mutations, 5 of whom were novel variants: 2 localized on ABCB4 (p.I587DfsX603, p.I738LfsX744) and 3 on ABCB11 (p.V284D, p.Q558H, p.P731S). The most severe phenotypes were associated with the variants p.I587DfsX603, p.I738LfsX744 and p.V284D. Moreover, the already described mutation p.N510S found in ABCB4 seems to be strictly involved in the onset of ICP in that particular patient. CONCLUSIONS: Our data support the hypothesis of a significant involvement of ABCB4 mutations in the onset of ICP, but also confirm an important role for ABCB11 mutations in increasing the susceptibility to cholestasis of pregnancy.