TM6SF2 and MBOAT7 Gene Variants in Liver Fibrosis and Cirrhosis

Previous large-scale genetic studies identified single nucleotide polymorphisms (SNPs) of the TM6SF2 and MBOAT7 genes as risk factors for alcoholic liver cirrhosis and non-alcoholic fatty liver disease. In this study, we tried to evaluate the association between TM6SF2 variant rs58542926 and MBOAT7 variant rs641738 and the risk of hepatic fibrosis or liver cirrhosis of different etiology. In parallel, we also aimed to evaluate whether these two SNPs modify the effects of the PNPLA3 rs738409 risk variant for the development of hepatic fibrosis and liver cirrhosis. The study was conducted at the Department of Gastroenterology, Lithuanian University of Health Sciences Hospital,and included 334 patients with liver cirrhosis, 128 patients with liver fibrosis, and 550 controls. SNPs were genotyped by quantitative PCR, using TaqMan allelic discrimination assays. Overall, TM6SF2 rs58542926 as well as MBOAT7 rs641738 were not linked to hepatic fibrosis, alcohol or hepatitis C virus induced liver cirrhosis in an Eastern European population. These genetic variations also didnot mediate the effect of PNPLA3 rs738409 SNP for liver developing liver fibrosis or liver cirrhosis

Acute and 14-Day Hepatic Venous Pressure Gradient Response to Carvedilol and Nebivolol in Patients With Liver Cirrhosis

Background and Objective: Alternative drug therapies are needed for the treatment of portal hypertension.[...

High frequency of the c.3207C>A (p.H1069Q) mutation in ATP7B gene of Lithuanian patients with hepatic presentation of Wilson’s disease

AIM: To investigate the prevalence of the ATP7B gene mutation in patients with hepatic presentation of Wilson’s disease (WD) in Lithuania

TM6SF2 and MBOAT7 Gene Variants in Liver Fibrosis and Cirrhosis

Previous large-scale genetic studies identified single nucleotide polymorphisms (SNPs) of the TM6SF2 and MBOAT7 genes as risk factors for alcoholic liver cirrhosis and non-alcoholic fatty liver disease. In this study, we tried to evaluate the association between TM6SF2 variant rs58542926 and MBOAT7 variant rs641738 and the risk of hepatic fibrosis or liver cirrhosis of different etiology. In parallel, we also aimed to evaluate whether these two SNPs modify the effects of the PNPLA3 rs738409 risk variant for the development of hepatic fibrosis and liver cirrhosis. The study was conducted at the Department of Gastroenterology, Lithuanian University of Health Sciences Hospital, and included 334 patients with liver cirrhosis, 128 patients with liver fibrosis, and 550 controls. SNPs were genotyped by quantitative PCR, using TaqMan allelic discrimination assays. Overall, TM6SF2 rs58542926 as well as MBOAT7 rs641738 were not linked to hepatic fibrosis, alcohol or hepatitis C virus induced liver cirrhosis in an Eastern European population. These genetic variations also did not mediate the effect of PNPLA3 rs738409 SNP for liver developing liver fibrosis or liver cirrhosis

Gene polymorphisms of micrornas in Helicobacter pylori-induced high risk atrophic gastritis and gastric cancer.

BACKGROUND AND AIMS: MicroRNAs (miRNAs) are known for their function as translational regulators of tumor suppressor or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNAs related genes have been shown to affect the regulatory capacity of miRNAs and were linked with gastric cancer (GC) and premalignant gastric conditions. The purpose of this study was to evaluate potential associations between miRNA-related gene polymorphisms (miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608) and the presence of GC or high risk atrophic gastritis (HRAG) in European population. METHODS: Gene polymorphisms were analyzed in 995 subjects (controls: n = 351; GC: n = 363; HRAG: n = 281) of European descent. MiR-27a T>C (rs895819), miR-146a G>C (rs2910164), miR-196a-2 C>T (rs11614913), miR-492 G>C (rs2289030) and miR-608 C>G (rs4919510) SNPs were genotyped by RT-PCR. RESULTS: Overall, SNPs of miRNAs were not associated with the presence of GC or HRAG. We observed a tendency for miR-196a-2 CT genotype to be associated with higher risk of GC when compared to CC genotype, however, the difference did not reach the adjusted P-value (odds ratio (OR) - 1.46, 95% confidence interval (CI) 1.03-2.07, P = 0.032). MiR-608 GG genotype was more frequent in GC when compared to controls (OR -2.34, 95% CI 1.08-5.04), but significance remained marginal (P = 0.029). A similar tendency was observed in a recessive model for miR-608, where CC + CG vs GG genotype comparison showed a tendency for increased risk of GC with OR of 2.44 (95% CI 1.14-5.22, P = 0.021). The genotypes and alleles of miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 SNPs had similar distribution between histological subtypes of GC and were not linked with the presence of diffuse or intestinal-type GC. CONCLUSIONS: Gene polymorphisms of miR-27a, miR-146a, miR-196a-2, miR-492, miR-492a and miR-608 were not associated with the presence of HRAG, GC or different histological subtypes of GC in European subjects

Characteristics of subject groups.

1<p>GC – gastric cancer; HRAG – high risk gastritis; <i>H. pylori</i> – <i>Helicobacter pylori.</i></p>2<p>Statistical analysis was performed globally for all three groups.</p

Genotype frequencies of <i>miR-27a</i>, <i>miR-146a</i>, <i>miR-196a-2</i>, <i>miR-492</i>, <i>miR-608</i> SNPs in controls, intestinal and diffuse-type GC subjects.

1<p>GC – gastric cancer; HRAG – high risk gastritis; aOR – adjusted odds ratio (age, sex, country); CI – confidence interval.</p

Genotype frequencies of <i>miR-27a</i>, <i>miR-146a</i>, <i>miR-196a-2</i>, <i>miR-492</i>, <i>miR-608</i> SNPs in controls, gastric cancer and high risk gastritis patients.

1<p>GC – gastric cancer; HRAG – high risk gastritis; aOR – adjusted odds ratio (age, sex, country); CI – confidence interval.</p>2<p>six patients with missing values on rs895819 were excluded from analysis.</p>3<p>five patients with missing values on rs2910164 were excluded from analysis.</p>4<p>one patient with missing values on rs11614913 was excluded from analysis.</p>5<p>three patients with missing values on rs4919510 were excluded from analysis.</p