Liver intestine-cadherin (CDH17) haplotype is associated with increased risk of hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC), the most common form of liver cancer, is a leading cause of cancer death worldwide. We previously showed that aberrant mRNA splicing of the liver intestine-cadherin gene CDH17 in liver tissues was triggered by the specific constellation of two CDH17 single nucleotide polymorphisms (651T and IVS6+35G). CDH17 aberrant splicing was highly associated with tumor dissemination and shorter survival of HCC patients. Consequently, it is highly relevant to assess whether the presence of these single nucleotide polymorphisms in the general population represents a risk to the development of HCC. EXPERIMENTAL DESIGN: We conducted a case-control study including 164 HCC and 99 cirrhosis patients and 293 healthy controls. Genotyping was done by PCR and direct sequencing. Odds ratio (OR) and chi2 analysis were used to analyze genotypes and haplotypes. RESULTS: Genotypes 651TT [OR, 2.62; 95% confidence interval (95% CI), 1.34-5.03] and IVS6+35 GG (OR, 1.95; 95% CI, 1.04-3.62) were highly associated with HCC disease. The 651T (C>T) and IVS6+35G (A>G) alleles were also overrepresented in HCC patients and, in particular, the T-G haplotype was the most prevalent in HCC patients when compared with healthy controls (OR, 1.57; 95% CI, 1.167-2.109; P=0.004), which was in agreement with the aberrant splicing observed in tumor tissues. There was no significant difference in genotype and allele frequencies between cirrhosis patients and controls. CONCLUSION: The functional T-G haplotype of CDH17 (651 C>T and IVS6+35A>G) is a genetic susceptibility factor for the development of HCC in a Chinese population.

Carotid intima-media thickness in patients with abdominal aortic aneurysms.

OBJECTIVE: The contribution of atherosclerosis to the development of Abdominal Aortic Aneurysms (AAA) is still controversial. Ultrasound scans can detect intima-media thickening of the carotid arteries as an early sign of atherosclerosis. The aim of this study was to investigate whether patients with Abdominal Aortic Aneurysms (AAAs) have thickened carotid IMT as patients with atherosclerotic peripheral arterial disease (PAD). METHODS: With high-resolution B-mode ultrasonography, the intima-media thickness (IMT) in the carotid arteries (right and left common carotid artery) was measured in AAA patients and compared with that of age and sex-matched patients with atherosclerotic peripheral arterial disease (PAD). A third group of healthy age and sex- matched control subjects were included for comparison. The corresponding carotid artery lumen was also determined in all groups. Comparison of the three groups was made by ANOVA. RESULTS: Fifty-eight AAA patients and 69% were men (mean age of 72.3 years) were studied. Aged and sex-matched groups comprised of 111 PAD patients and 71 healthy. The mean carotid IMT was highest in PAD patients (1.036+/-0.18mm). The values of controls and AAA patients were similar and significantly lower than that of atherosclerotic patients (0.875+/-0.11mm and 0.812+/-0.53mm respectively, both p<0.005 vs. PAD). Narrowing of the corresponding lumen was found in PAD patients compared with that of AAA patients, but no difference can be seen between healthy subjects and AAA patients. The mean carotid IMT was greater in men (P<0.05) in all studied groups, but no similar gender specificity was found in the lumen diameter. CONCLUSIONS: This study shows that the carotid artery IMT of AAA patients is similar to healthy subjects, but not as thick as patients with atherosclerotic disease. As carotid (IMT) is a surrogate marker of atherosclerosis, the findings support the notion that the formation of AAA may not be fully atherosclerosis-dependent. Gender may be a confounding factor for carotid intima-media thickening.

Plasma fibrinogen level: an independent risk factor for long-term survival in Chinese patients with peripheral artery disease?

Fibrinogen, an inflammatory marker as well as a fundamental part of the coagulation cascade, is suggested to play a significant role in the pathogenesis of atherosclerosis and complications of atherothrombotic diseases. The aim of this study was to determine if plasma fibrinogen is an independent risk factor for long-term survival in patients with peripheral artery disease (PAD). Altogether, 139 Chinese patients (88 men, 51 women) with PAD were consecutively recruited for the study. Atherothrombotic risk factors and fibrinogen levels were determined at presentation, and all patients were followed up for mortality prospectively. The mean follow-up was 6 years. All variables were first correlated with survival rates using Kaplan-Meier analysis and compared by means of the log-rank test. Significant risk factors were identified, and multivariate Cox regression analysis was used to evaluate the independent contribution of the fibrinogen level to the risk of mortality. During follow-up, 95 patients (68.3%) died. The overall survival rate was 77.7% at 3 years, 56.8% at 5 years, and 31.2% at 10 years (standard errors 0.05, 0.06, and 0.07, respectively). All-cause mortality rate increased with an elevated fibrinogen level. Eighty percent of patients with a fibrinogen level > 3.4 g/L had a survival time of less than 3 years (p = 0.002). This relation was also demonstrated within patients with critical ischemia. The plasma fibrinogen level was thus identified as an independent risk factor for mortality in PAD patients after adjusting for confounding factors.