Effects of common haplotypes of the ileal sodium dependent bile acid transporter gene on the development of sporadic and familial colorectal cancer: A case control study

<p>Abstract</p> <p>Background</p> <p>The genetics of sporadic and non-syndromic familial colorectal cancer (CRC) is not well defined. However, genetic factors that promote the development of precursor lesions, i.e. adenomas, might also predispose to CRC. Recently, an association of colorectal adenoma with two variants (c.507C>T;p.L169L and c.511G>T;p.A171S) of the ileal sodium dependent bile acid transporter gene (<it>SLC10A2</it>) has been reported. Here, we reconstructed haplotypes of the <it>SLC10A2 </it>gene locus and tested for association with non-syndromic familial and sporadic CRC compared to 'hyper-normal' controls who displayed no colorectal polyps on screening colonoscopy.</p> <p>Methods</p> <p>We included 150 patients with sporadic CRC, 93 patients with familial CRC but exclusion of familial adenomatous polyposis and Lynch's syndrome, and 204 'hyper-normal' controls. Haplotype-tagging <it>SLC10A2 </it>gene variants were identified in the Hapmap database and genotyped using PCR-based 5' exonuclease assays with fluorescent dye-labelled probes. Haplotypes were reconstructed using the PHASE algorithm. Association testing was performed with both SNPs and reconstructed haplotypes.</p> <p>Results</p> <p>Minor allele frequencies of all <it>SLC10A2 </it>polymorphisms are within previously reported ranges, and no deviations from Hardy-Weinberg equilibrium are observed. However, we found no association with any of the <it>SLC10A2 </it>haplotypes with sporadic or familial CRC in our samples (all P values > 0.05).</p> <p>Conclusion</p> <p>Common variants of the <it>SLC10A2 </it>gene are not associated with sporadic or familial CRC. Hence, albeit this gene might be associated with early stages of colorectal neoplasia, it appears not to represent a major risk factor for progression to CRC.</p

Transient elastography discloses identical distribution of liver fibrosis in chronic hepatitis C between HIV-negative and HIV-positive patients on HAART

<p>Abstract</p> <p>Objective</p> <p>Progressive immunodeficiency associated with HIV-infection leads to a progressive course of liver disease in HIV/HCV-co-infected patients. Highly active antiretroviral therapy (HAART) efficiently restores and preserves immune functions and has recently been demonstrated to also result in reduced liver-related mortality in HIV/HCV-co-infected patients.</p> <p>Methods</p> <p>To analyse differences in current liver fibrosis as a possible effect of HAART on fibrosis progression we assessed hepatic fibrosis by transient elastography in a cross-sectional comparison between HCV-mono-infected and HIV/HCV-co-infected patients presenting at our outpatient department in 2007.</p> <p>Results</p> <p>Overall, we did not find any difference in the distribution of liver stiffness between mono- (n = 84) and double-infected (n = 57) patients (14.4 kPa (10.8 - 18.2) versus 12.4 kPa (9.1 - 16.1), mean (95%-CI)). However, in the 8 HIV+ patients with CD4 counts < 200/μl liver stiffness was markedly greater (18.4 kPa (0.8 - 36.0)) than in HIV+ patients with preserved immunity (11.5 kPa (8.4 - 15.0)).</p> <p>Conclusions</p> <p>These findings are in line with other data that show an improved prognosis of chronic hepatitis C in HIV+ patients under effective HAART, and may be a hint that fibrosis progression in well-treated HIV+ patients will no longer be different from that in HCV-mono-infected patients.</p

Supplementary Material for: Effects of Gene Variants Controlling Vitamin D Metabolism and Serum Levels on Hepatic Steatosis

<b><i>Background/Aims:</i></b> Common genetic variations in vitamin D metabolism are associated with liver stiffness. Whether these genes are implicated in hepatic steatosis remains unclear. Here we aimed to analyse the association of common vitamin D pathway gene variants with liver steatosis. <b><i>Methods:</i></b> Liver steatosis was assessed non-invasively in 241 patients with chronic liver conditions by controlled attenuation parameter (CAP). The following polymorphisms were genotyped using TaqMan assays: group-specific component (<i>GC</i>) rs7041, 7-dehydrocholesterol reductase (<i>DHCR7</i>) rs12785878, cytochrome P450 2R1 (<i>CYP2R1</i>) rs10741657, ­vitamin D receptor (<i>VDR</i>) rs7974353. Chemiluminescence immunoassay determined serum 25-hydroxyvitamin D (25(OH) D) concentrations. <b><i>Results:</i></b> Vitamin D deficiency (defined by 25(OH)D concentrations <20 ng/mL) occurred in 66% of patients. Median CAP was 296 (100–400) dB/m. Patients with advanced steatosis (CAP ≥280 dB/m) had significantly (<i>p</i> = 0.033) lower 25(OH)D levels as compared to patients with CAP <280 dB/m. Moreover, the rare allele [T] in <i>GC</i> rs7041 was significantly (<i>p</i> = 0.018) associated with higher 25(OH)D levels in patients with CAP <280 dB/m. However, <i>GC</i>, <i>DHCR7,</i> <i>CYP2R1</i>, and <i>VDR</i> polymorphisms were not related to liver steatosis and obesity traits. <b><i>Conclusions:</i></b> Higher CAP values are associated with low serum 25(OH)D concentrations but not with common vitamin D pathway gene variants