ChREBP gene polymorphisms are associated with coronary artery disease in Han population of Hubei province

BackgroudChREBP regulates lipogenesis and glucose utilization in the liver. Current reports suggest a contradictive association between rs3812316 of this gene and triglyceride level. We hypothesized the polymorphisms in ChREBP gene were associated with CAD in Chinese population.MethodsThe ChREBP gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods in 200 controls and 310 CAD patients. Serum lipids and glucose concentrations were measured in all subjects. Haplotypes were constructed based on rs3812316, rs7798357 and rs1051921. All the data were analyzed using SPSS14.0, PLINK1.07 and SHEsis software.ResultsThe rare allele G of rs3812316 was significantly lower in the CAD group after adjusting for age, sex, BMI, SBP and DBP (OR^a = 0.589, 95%CI = 0.361–0.961, P = 0.034). No significant differences between cases and controls were found in genotype or allele distributions of rs7798357, rs17145750 and rs1051921. Haplotype CGC was significant higher in CAD group (P < 0.01, OR = 2.364, 95%CI = 1.608–3.474), while haplotypes GGC, CGT, CCC were significant lower in CAD group (P < 0.05).ConclusionsThe rs3812316 and the haplotypes in ChREBP gene appeared to be related to high susceptibility to CAD.     

Effect of obesity on the association between ATF3 gene haplotypes and C-reactive protein level in Taiwanese

ObjectiveATF3 has traditionally been related to various inflammatory processes. Our aim was to test the statistical association between variations in the ATF3 gene and levels of nine serum inflammatory markers, including C reactive protein (CRP), in a Taiwanese population using interaction analysis.MethodsA sample population of 604 Taiwanese subjects was enrolled. Five tagging single nucleotide polymorphisms of the ATF3 gene from the Han Chinese HapMap Database were selected and genotyped.ResultsWith or without adjustment for clinical covariates, ATF3 genotypes were found to be associated with CRP levels but not with other inflammatory marker levels. Minor alleles of 2 of the 5 ATF3 SNPs were associated with decreased CRP levels predominantly in non-obese subjects (Bonferoni P = 0.018, and P = 0.002 for rs11571530, and rs10475, respectively). Two haplotypes inferred from the 5 SNPs, GATTA and TACCA, were also associated with increased or decreased CRP levels, respectively, in non-obese subjects (Bonferoni P = 0.012 and P = 0.01, respectively) but not in obese subjects. Interaction analysis revealed interaction of obesity with an ATF3 genotype associated with a high CRP level (interaction P = 0.006 for SNP rs10475). An effect of obesity on CRP level was also noted in haplotype interaction analysis (interaction P = 0.019 for haplotype TACCA).ConclusionsATF3 polymorphisms are independently associated with CRP levels in Taiwanese subjects. Further, ATF3 genotypes/haplotypes interact with obesity to set CRP levels. These findings may have implications for the prediction of atherosclerotic disease.     

Polymorphisms in the CC-chemokine receptor-2 (CCR2) and -5 (CCR5) genes and risk of myocardial infarction among Tunisian male patients

ObjectivesThe aim of the present study was to investigate the association between CCR2-Val64Ile and CCR5-Δ32 variants and the estimation of haplotypes with MI in a sample of the Tunisian population.Design and methodsA total of 290 unrelated MI patients and 282 healthy controls were studied. The CCR2-Val64Ile and CCR5-Δ32 variants were analyzed by PCR-RFLP.ResultsSubjects carrying at least one copy of the CCR5-deletion allele were significantly more common in the control group, suggesting an atheroprotective effect (adjusted OR = 0.44, 95% CI = 0.28–0.72, p = 0.001). Haplotype analysis showed that MI patients had significantly less 64Val-Del haplotype (9.9% vs. 21.3%, OR = 0.30, 95% CI = 0.21–0.43, p < 0.001) and 64Ile-Ins haplotype (12.3% vs. 16.7%, OR = 0.58, 95% CI = 0.42–0.80, p < 0.001).ConclusionA protective effect of the CCR5-Δ32 polymorphism against MI in the Tunisian population was found.     

Effect of obesity on the association between common variations in the HNF1A gene region and C-reactive protein level in Taiwanese

BackgroundThe level of C-reactive protein (CRP), an inflammatory biomarker that predicts future cardiovascular events, is a heritable trait that has been associated with variants of CRP and hepatic nuclear factor-1α (HNF1A) genes. Our aim was to test the statistical association between HNF1A genotypes/haplotypes and serum CRP level in Taiwanese.MethodsA sample population of 617 Taiwanese subjects (all Han-Chinese origin) was enrolled. Five HNF1A single nucleotide polymorphisms (SNPs) rs1920792, rs1169288, rs7310409, rs2464196, rs1169310 were genotyped and analyzed.ResultsAfter adjusting for clinical covariates, minor alleles of all the 5 study SNPs were associated with decreased CRP level (P = 0.0078, P = 0.0107, P = 0.0006, P = 0.0004 and P = 0.0003, respectively). A common haplotype (TGATA) tagged by the minor alleles of study SNPs was associated with significantly decreased CRP level (P = 0.0112). Subgroup analysis revealed that the association between HNF1A genotypes and CRP level occurred only in non-obese subjects.ConclusionsHNF1A polymorphisms are independently associated with CRP level in Taiwanese. Further, HNF1A genotypes interact with obesity to set CRP level, revealing that genetic determinants for CRP level may be different between obese and non-obese individuals.     

A single nucleotide polymorphism in LRP2 is associated with susceptibility to Alzheimer's disease in the Chinese population

BackgroundLRP2 (also called megalin) plays a potential key role in the pathogenesis of Alzheimer's disease (AD). Recently, one genome-wide association study has revealed that the rs3755166 (G/A) polymorphism located in the LRP2 promoter is associated with development of AD in Caucasians, while there are no studies on the association LRP2 of with AD risk in Asians.MethodsTo evaluate the relationship between the rs3755166 polymorphism of the LRP2 gene and AD in the ethnic Chinese Han, we conducted a case-control study (n = 361, age > 50) to determine the prevalence of one common single-nucleotide polymorphism (SNP) of LRP2 (rs3755166) in patients with AD in Chinese population of Mainland China, and clarified whether this polymorphism is a risk factor for AD.ResultsThe prevalence of the minor allele (A) in the rs3755166 polymorphism was significantly different in AD patients and control subjects (P < 0.05). The rs3755166 polymorphism was associated with AD in the ethnic Chinese Han (OR = 1.378, 95% CI: 1.017-1.867, P = 0.039), and the results were not influenced by age, gender, or APOE status (P = 0.441, P = 0.94, P = 0.432, respectively).ConclusionOur data revealed the allele (A) of the rs3755166 polymorphism within LRP2 gene may contribute to AD risk in the Chinese Han Population.     

Folate and choline metabolism gene variants and development of uterine cervical carcinoma

ObjectiveIt has been reported that aberrant DNA methylation can be associated with HPV infection and cervical tumorigenesis. The aim of this study was to evaluate the possibility that polymorphic variants of genes that may affect DNA methylation status are associated with the risk of cervical cancer in the Polish population.Design and methodEmploying PCR-RFLPs and HRM analyses, we examined the prevalence of BHMT Arg239Gln (rs3733890), MTR Asp919Gly (rs1805087), MTHFR Ala222Val (rs1801133), MTHFD1 Arg653Gln (rs2236225) and MTRR Ile22Met (rs1801394) genotypes and alleles in patients with advanced cervical cancer (n = 124) and controls (n = 168).ResultsThe odds ratio (OR) for BHMT Gln/Gln genotype was 0.433 (95% CI = 0.1780–1.054; p = 0.0602). The OR for patients having the BHMT Arg/Gln or Gln/Gln genotypes was 0.579 (95% CI = 0.3622–0.924; p = 0.0216). We also observed a significantly higher frequency of the BHMT 239Gln allele in controls than in patients, p = 0.0165. The genotype and allele frequencies of the MTR Asp919Gly, MTHFR Ala222Val, MTHFD1 Arg653Gln and MTRR Ile22Met gene variants did not display statistical differences between patients with cervical cancer and controls. We also did not find a significant association between the distribution of any genotypes or alleles and cancer characteristics.ConclusionOur results might suggest the protective role of the BHMT 239Gln variant in cervical cancer incidence.     

The RANTES gene promoter polymorphisms are associated with the risk of atherothrombotic cerebral infarction in Northern Han Chinese

BackgroundRegulated upon activation, normal T-cell expressed and secreted (RANTES) plays an important role in the inflammatory process. This study is aimed at evaluating the potential association of the ? 403G/A (rs2107538) and ? 28C/G (rs2280788) polymorphisms of the RANTES gene promoter with the risk of atherothrombotic cerebral infarction (ACI) in Northern Han Chinese.MethodA total of 314 patients with ACI and 389 unrelated aged-matched healthy controls were recruited. Their genotypes of the RANTES gene promoter ? 403G/A (rs2107538) and ? 28C/G (rs2280788) were analyzed by multiplex polymerase chain reaction (multiplex PCR) and multiplex SNaPshot analysis. The potential association of genotyping and allele frequencies with ACI in this population was assessed statistically.ResultsThe frequencies of ? 403AA genotype and A allele in ACI male patients were significantly higher than that in healthy controls (P = 0.007, P = 0.009, respectively). Female patients were not different. Multiple logistic regression analysis revealed that the ? 403AA genotype in males was significantly associated with an increased risk of ACI, even after adjusting for confounding factors (OR = 4.344; 95% CI = 1.969–9.582; P < 0.001). Although there was no significant association of the ? 28C/G polymorphism with ACI, the A-₄₀₃C-₂₈ haplotype was significantly associated with an increased risk of ACI in Han Chinese [OR = 1.56, 95% CI = 1.23–1.98, P < 0.001].ConclusionsOur data suggest that the ? 403AA genotype and A allele of the RANTES promoter were associated with increased risk for the development of ACI in male Northern Han Chinese.     

Genetic association of rs11610206 SNP on chromosome 12q13 with late-onset Alzheimer's disease in a Han Chinese population

BackgroundSeveral genome wide screens and candidate gene studies have implicated the chromosome 12p13 locus as possibly harboring genetic variants predisposed to late-onset Alzheimer's disease (LOAD). Recently, the strongest significant association was reported for the single nucleotide polymorphism (SNP) rs11610206 on chromosome 12q13 in an independent genome-wide association study (GWAS) in Caucasians.MethodsWe investigated whether the SNP on chromosome 12q13 was associated with LOAD in a Han Chinese population. The common rs11610206 SNP on chromosome 12q13 was genotyped using MALDI-TOF mass spectrometry in 322 patients with LOAD and in 391 healthy controls matched for sex and age.ResultsPatients with LOAD had higher frequencies of T allele (56.0% versus 49.2%) compared with controls [odds ratio (OR) = 1.45, 95% confidence intervals (CI) = 1.08–1.95, and P = 0.01]. After stratification by APOE ε4-carrying status, the T allele of rs11610206 was significantly associated with LOAD only in APOE ε4 allele carriers (OR = 2.05, 95% CI = 1.21–3.47, and P = 0.007). Furthermore, multivariate logistic regression analysis showed that the TT genotype carriers demonstrated a 1.52-fold risk when compared with (TC + CC) genotype carriers (OR = 1.52, 95% CI = 1.07–2.17, and P = 0.02).ConclusionsThis study demonstrates an association of rs11610206 polymorphism locus on chromosome 12q13 with risk for LOAD in Han Chinese.     

Association of STAT4 polymorphisms with susceptibility to primary membranous glomerulonephritis and renal failure

BackgroundMembranous glomerulonephritis (MGN) is one of common causes of idiopathic nephrotic syndrome in adults, and 25% of MGN patients proceed to end-stage renal disease. STAT4 gene polymorphisms have been reported to be associated with many inflammatory diseases. The objective of this study was to clarify the relationship between STAT4 gene polymorphisms and the pathogenesis of MGN.MethodsWe investigated the association of three STAT4 gene polymorphisms (rs3024912, rs3024908, and rs3024877) with the susceptibility to MGN in 403 Taiwanese populations (138 MGN patients and 265 controls).ResultsThe results indicated that the statistically significant difference in genotype frequency distribution was found at rs3024908 SNP in MGN patients and control groups (p = 0.014). In addition, the individuals with the GG genotype at rs3024912 SNP may have a higher risk in kidney failure of MGN patients (adjusted odds ratio [OR] = 3.255; 95% confidence interval [CI] = 1.155–9.176, p = 0.026).ConclusionsOur data provide a new information that the STAT4 (rs3024912 and rs3024908) polymorphisms may be the underlying cause of MGN, and these polymorphisms revealed by this study warrant further investigation.     

Pro-inflammatory and anti-inflammatory cytokines in acute ischemic stroke and their relation to early neurological deficit and stroke outcome

ObjectivesOur aim was to explore (i) the difference in concentration of IL-6, TNF-α and IL-10 between acute ischemic stroke patients and control individuals; (ii) the association of plasma cytokine concentration with stroke severity at admission assessed by NIHSS and stroke outcome in 90 days assessed by Barthel index (BI) and modified Rankin scale (mRS).Materials and methodsStudy included 68 stroke patients admitted within 12 h of symptoms onset and 71 controls.ResultsIL-6 was increased in patients relative to controls (P = 0.035) and this increase was associated with severe stroke (P = 0.007) and worse outcome (P = 0.030 and 0.019; assessed by BI and mRS, respectively), whereas IL-10 was decreased (P = 0.044) and associated with better outcome (P = 0.043). TNF-α did not differ between studied groups (P = 0.302).ConclusionsIncreased IL-6 and reduced IL-10 concentrations are present in early stroke period and are associated with a degree of neurological deficit and/or stroke outcome.     

High resolution melting analysis for the detection of SLC25A13 gene mutations in Taiwan

BackgroundCitrin, encoded by SLC25A13 gene, is a mitochondrial solute transporter with a crucial role in urea, nucleotide and protein synthesis. SLC25A13 mutations cause two phenotypes, adult-onset type II citrullinemia and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). This study aimed to develop a high resolution melting (HRM) analysis for SLC25A13 mutation scanning and determine the carrier rate in Taiwan.MethodsDNAs from healthy subjects (n = 479), and patients with hepatocellular carcinoma (HCC, n = 100) and NICCD (n = 5) were scanned in exons 6, 9, 11, 16, and 17 and parts of introns of SLC25A13 using HRM analysis. All mutations detected by HRM analysis were further confirmed by TaqMan method and/or direct sequencing.ResultsIn healthy subjects, seventeen carriers with mutants c.851_854del (n = 10), c.1638_1660dup, c.615 + 5G > A (n = 4), and two novel mutants, c.475C > T and c.1658G > A, were detected. The frequency of carriers was about 1/28. In patients with HCC, there were only 2 carriers with c.851_854del mutant. Patients with NICCD (n = 5) diagnosed during 2007 and 2008, harbored compound heterozygous mutations c.851_854del/c.1177 + 1G > A, c.851_854del/c.1638_1660dup (n = 2), c.851_854del/c.615 + 5G > A, and c.1638_1660dup/c.615 + 5G > A.ConclusionsHRM analysis is a simple, rapid and robust method for detecting SLC25A13 mutations in clinical laboratories. SLC25A13 mutations may not be a major contributor to the pathogenesis of HCC in Taiwan.     

Polymorphism at the mucin-like protocadherin gene influences susceptibility to gallstone disease

BackgroundGallstone disease (GSD) is a common disease that can be caused by environmental influences, common genetic factors and their interactions. Mucin glycoproteins may be one important factor for GSD. We conducted a case–control study to investigate the relationship between the mucin-like protocadherin (MUPCDH) gene polymorphisms and GSD.MethodsThe study included 452 GSD cases and 491 healthy controls who had no evidence of gallstones by ultrasound examination. Two common tagging single nucleotide polymorphism (SNP) rs3758650 and rs7932167, and four non-synonymous SNPs rs34362213, rs2740375, rs7108757 and rs2740379 were genotyped. The genetic effects were evaluated using the multivariate regression model.ResultsThe genotypes of these SNPs were all in Hardy–Weinberg equilibrium. Three non-synonymous SNPs (rs34362213, rs7108757 and rs2740379) were monomorphic. The single SNP analysis showed two SNPs (rs7932167 and rs2740375) were not associated with GSD and only SNP rs3758650 had the association of the presence of GSD with an odds ratio (OR) of 1.59 (adjusted P = 0.013) for the AG genotype and 5.82 (adjusted P = 0.007) for the AA genotype when compared with the reference GG genotype. The haplotype analysis of the three polymorphic SNPs showed GCA was significant for GSD (adjusted p = 0.001) with an odds ratio (OR) of 1.41 when compared to other haplotypes.ConclusionsThe MUPCDH genetic polymorphism rs3758650 was considered a genetic marker to predict symptomatic GSD subjects. It may be of importance for GSD patients with the risk SNPs to be frequently checked because they may develop symptomatic GSD.     

APOE haplotypes are associated with human longevity in a Central Italy population: evidence for epistasis with HP 1/2 polymorphism

BackgroundApolipoprotein E (APOE) functional haplotypes determined by rs429358 and rs7412 SNPs have been extensively studied and found to be one of the most consistent association in human longevity studies. However, the search for longevity-determining genes in human has largely neglected the operation of genetic interactions.MethodsAPOE haplotypes have been determined for 1072 unrelated healthy individuals from Central Italy, 18–106 years old, divided into three gender-specific age classes defined according to demographic information and accounting for the different survival between sexes. The epistasis between APOE haplotypes and Haptoglobin (HP) 1/2 polymorphism was tested according to three-way contingency table analysis by a log-linear model.ResultsAPOE genotype and haplotype distributions differ significantly along the age classes (Genotype: p = 0.014; Haplotype: p = 0.005) with APOE*ε4 genotype status and haplotype displaying negative association (Genotype: O.R. = 0.377, p = 0.002, Haplotype: O.R. = 0.447, p = 0.005). A significant interaction between APOE*ε4 genotype status, HP 1/2 genotype and age classes is reported (p = 0.006).ConclusionAPOE haplotypes are significantly associated with longevity in our population. Of note, HP*1/*1 genotype seems to protects APOE*ε4 carriers from age-related negative selection. Collectively, these results also suggest and claim for further investigations on APOE/HP interaction in other age-related diseases such as Alzheimer's disease, atherosclerosis and Parkinson's disease.     

Plasma adiponectin as an independent predictor of early death after acute intracerebral hemorrhage

BackgroundHyperadiponectinemia or hypoadiponectinemia is associated with different diseases. There is a paucity of data on circulating plasma adiponectin concentrations in human intracerebral hemorrhage (ICH). We investigated the plasma adiponectin concentrations in patients with intracerebral hemorrhage, and analyzed the correlation of adiponectin with the severity of brain injury and early mortality after ICH.MethodsThirty controls and 86 patients with acute ICH were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5, and 7 after ICH. Their concentrations were measured by enzyme-linked immunosorbent assay.ResultsAfter ICH, plasma adiponectin level of the patients increased immediately within 6 h, peaked within 24 h, plateaued at day 2, and decreased gradually thereafter. It was substantially higher than that in the controls in a period of 7 days. A multivariate analysis showed plasma adiponectin level was an independent predictor for 1-week mortality (odds ratio, 1.199; 95% CI: 1.035–1.389; P = 0.015) and that it was associated with Glasgow coma scale (GCS) score (t = ? 3.596, P = 0.001) and plasma C-reactive protein level (t = 4.194, P < 0.001). A receiver operating characteristic curve identified that a plasma adiponectin level > 16.4 μg/ml predicted the 1-week mortality of patients with a sensitivity of 65.6% and a specificity of 90.7% (AUC, 0.789; 95% CI: 0.688–0.870). The predictive value of adiponectin concentration was significantly lower than that of GCS score (P = 0.007) and hematoma volume (P = 0.022). Adiponectin could not improve the predictive values of GCS score (P = 0.317) and hematoma volume (P = 0.226).ConclusionsAdiponectin is an independent indicator of early death and may play an anti-inflammatory role after intracerebral hemorrhage.     

Common variant in GAB2 is associated with late-onset Alzheimer's disease in Han Chinese

BackgroundGRB-associated binding protein 2 (GAB2) may function as a risk factor in the pathogenesis of Alzheimer disease (AD). A recent large genome-wide association study (GWAS) has identified a significant association of rs10793294 polymorphism within the GAB2 gene with AD in Caucasians. While there are no studies on the association of rs10793294 polymorphism with AD risk in the Chinese population.MethodsThe study investigated 358 sporadic late-onset AD (LOAD) and 366 healthy controls matched for sex and age in a Han Chinese population. The rs10793294 polymorphism within the GAB2 gene was genotyped using MALDI-TOF mass spectrometry.ResultsThe C allele of the rs10793294 polymorphism within GAB2 was significantly associated with an increased risk of LOAD (OR = 1.33, 95% CI = 1.04–1.72, P = 0.029). Significance was observed in APOEε4 carriers (genotype P = 0.039, allele P = 0.016). While in APOE ε4 non-carriers, significant differences were observed in alleles (P = 0.039) but not in genotypes (P = 0.304). Logistic regression revealed that rs10793294 polymorphism was still strongly associated with LOAD in dominant model (OR = 2.58, 95% CI = 1.22–5.45, P = 0.013) and additive model (OR = 1.38, 95% CI = 1.05–1.80, P = 0.020) after adjusting for age, gender, and the APOE ε4 status.ConclusionsOur findings implicate GAB2 as a susceptibility gene for LOAD in Han Chinese.     

Potential role of GABAA receptor subunit; GABRA6, GABRB2 and GABRR2 gene polymorphisms in epilepsy susceptibility and pharmacotherapy in North Indian population

BackgroundGABA_A receptors influence the susceptibility to seizures, and variations in the receptor genes can contribute to antiepileptic drug resistance also.MethodsWe investigated the possible associations of single nucleotide polymorphisms (SNPs) present in GABRA6 c. 1512 T>C, GABRB2 c. 1412 C>T, and GABRR2 c. IVS2C>G genes of GABA_A receptors in epilepsy susceptibility and drug resistance in northern Indian patients with epilepsy. After screening a total of 202 healthy controls and 401 epilepsy patients were enrolled in study. The genotyping was done by PCR-RFLP methods.ResultsThe GABRA6 c. 1512 T>C, polymorphism was conferring risk for epilepsy susceptibility for TC (P = 0.018), CC (P = 0.0001) genotype and for C allele (P = 0.0002). Another polymorphism GABRB2 c. 1412 C>T was also conferring high risk for epilepsy susceptibility CT (P = 0.012), TT (P = 0.778) genotype and for variant T allele (P = 0.034) but was not associated with drug resistance. No association was found with epilepsy susceptibility or with drug resistance in case of GABRR2 c. IVS2C>G gene polymorphism.ConclusionOverall, our findings suggest significant involvement of alpha (GABRA6) and beta (GABRB2) subunits of GABA_A receptor in epilepsy susceptibility in north Indian population.     

Prediction of the neurological outcome with intrathecal high mobility group box 1 and S100B in cardiac arrest victims: a pilot study

ObjectivesTo investigate whether high mobility group box 1 (HMGB1) and S100B in cerebrospinal fluid (CSF) and the serum predict the neurological outcome in patients resuscitated from out-of-hospital cardiac arrest (OHCA).Materials and methodsThis study was designed as a prospective observational study. Twenty-five patients, who received standard cardiopulmonary resuscitation and post-resuscitation intensive care, were enrolled in this study. The patients were divided into two groups according to Glasgow-Pittsburgh Cerebral Performance categories (CPCs) at 6 months after return of spontaneous circulation (ROSC), Group G (n = 7, CPC 1 or 2) and Group P (n = 18, CPC ≥ 3). Their blood samples were taken at 6, 24, and 48 h after ROSC. The patients, whose CSF was sampled at 48 h, were also divided into either sub-Group G (n = 6) or sub-Group P (n = 8) at 6 months after ROSC.ResultsHMGB1 and S100B in CSF in sub-Group P were significantly higher than those in sub-Group G (HMGB1, <1.0 vs. 12.4 ng/ml, P = 0.009; S100B, 2.68 vs. 84.2 ng/ml, P = 0.007, respectively). HMGB1 in CSF was strongly correlated with S100B (σ = 0.81, P = 0.001). HMGB1 was elevated in serum at 6 h and normalized within 48 h after ROSC without any significant differences between the two groups. Serum S100B in Group P was significantly higher than that in Group G at each time point.ConclusionsThe significant elevations of HMGB1 and S100B in CSF, and S100B in serum are associated with the neurologically poor outcome in OHCA patients.     

Preliminary evidence of a reduced serum level of fibroblast growth factor 19 in patients with biopsy-proven nonalcoholic fatty liver disease

ObjectivesWe sought to determine whether serum concentrations of fibroblast growth factor 19 (FGF19) – an ileum-derived enterokine which plays a role in the control of glucose and lipid homeostasis – are altered in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD).Design and methodsSerum levels of FGF19 were measured using enzyme-linked immunosorbent assay in 91 patients with biopsy-proven NAFLD and 74 controls.ResultsFGF19 levels were significantly lower in patients with biopsy-proven NAFLD (median: 130 pg/mL) than in controls (median: 210 pg/mL, P < 0.001). Serum FGF19 levels were significantly but modestly associated with hepatocyte ballooning scores in univariate analysis (r = ? 0.25, P < 0.05) but not after adjustment for potential confounders (β = ? 0.18; t = 1.78, P = 0.08).ConclusionsThis pilot study suggests that serum FGF19 levels are decreased in patients with NAFLD but are not independently associated with liver histology findings.     

Identification of pharmacogenetic predictors of lipid-lowering response to atorvastatin in Chilean subjects with hypercholesterolemia

BackgroundStatins are normally the first-line therapy for hypercholesterolemia (HC); however, the lipid-lowering response shows high interindividual variation. We investigated the effect of four polymorphisms in CYP3A4, CYP3A5 and ABCB1 genes on response to atorvastatin and CYP3A4 activity in Chilean subjects with HC.MethodsA total of 142 hypercholesterolemic individuals underwent atorvastatin therapy (10 mg/day/1 month). Serum lipid levels before and after treatment were measured. Genetic variants in CYP3A4 (? 290A>G, rs2740574), CYP3A5 (6986A>G, rs776746) and ABCB1 (2677G>A/T, rs2032582 and 3435C>T, rs1045642) were analyzed by PCR-RFLP. CYP3A4 enzyme activity in urine samples was assessed through determination of 6β-hydroxycortisol/cortisol free ratio (6βOHC/FC).ResultsAfter 4 weeks of therapy, a significant reduction in total cholesterol (TC) and LDL-c was observed (P < 0.001). The G allele for ? 290A>G polymorphism was related to higher percentage of variation in TC and LDL-c (P < 0.001). Moreover, same allele was associated with higher HDL-c variation (P = 0.017). In addition, CYP3A4 enzyme activity was lower in subjects carrying this polymorphism (P = 0.009). No differences were observed for CYP3A5 and ABCB1 variants.ConclusionOur results suggest that presence of G allele for ? 290A>G polymorphism determines a better response to atorvastatin, being also associated with lower CYP3A4 activity in vivo, causing an increased atorvastatin activity.