Klotho KL-VS genotype is involved in blood pressure regulation

Background and aimsGenome-wide linkage analysis studies reported the importance of the long arm of chromosome 13 in systolic blood pressure regulation. Therefore, isolating a genetic variant related to this chromosomal region could be challenging. Klotho KL-VS allele is located on this chromosomal region and its relationships with cardio-vascular risk factors need extensive investigations. The aim of the present study is to examine whether the klotho KL-VS genotype is associated with cardio-vascular risk factors, more particularly hypertension, in two independent cohorts. A secondary objective was to investigate relationships with antihypertensive treatment, arterial stiffness and carotid artery parameters.Methods and resultsA total of 1023 French individuals were genotyped for klotho KL-VS. Participants were part of the French ERA and STANISLAS cohorts. In both cohorts, klotho KL-VS/KL-VS genotype was significantly associated with lower systolic blood pressure and pulse pressure when compared to homozygous and heterozygous more frequent (WT) allele carriers (p = 0.003 and p < 0.001 respectively). Antihypertensive treatment stratification confirmed the previous significant associations, while a significant interaction between klotho KL-VS genotype and antihypertensive treatment was also interestingly found (0.019 for p interaction).ConclusionKlotho KL-VS/KL-VS genotype may be associated with decreased cardio-vascular risk and may interact with antihypertensive treatment in order to reduce blood pressure. This finding could lead to identify subgroups of hypertensive adults who might benefit antihypertensive drug therapies.     

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.     

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.     

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.     

The ratio of serum leptin to adiponectin provides adjunctive information to the risk of metabolic syndrome beyond the homeostasis model assessment insulin resistance: the Korean Genomic Rural Cohort Study

BackgroundLeptin and adiponectin are adipokines, shown to have opposing functions for fat metabolism and development of metabolic syndrome. We determined if the ratio of serum leptin to adiponectin (L/A ratio) adjunctively contributes to the risk of metabolic syndrome beyond the homeostasis model assessment of insulin resistance (HOMA-IR).MethodsThis study included 1532 men and 1856 women, aged 40–70 y assessed in the Korean Genomic Rural Cohort Study from 2005 to 2008. The serum concentrations of adiponectin and leptin were measured by radioimmunoassay. Area under the receiver operating characteristic curve (AUROC) analyses were used to describe the ability of L/A ratio and HOMA-IR to differentiate between subjects with and without metabolic syndrome.ResultsThere were no significant differences in the ability of L/A ratio and HOMA-IR to predict metabolic syndrome (AUROC of L/A ratio vs. HOMA-IR, 0.771 vs. 0.774, p = 0.8006 for men; 0.677 vs. 0.691, p = 0.3088 for women). There was a significant adjunctive contribution by the L/A ratio, beyond that of HOMA-IR, to the risk of metabolic syndrome in men (p < 0.0001 with 0.028 increased AUROC) and women (p = 0.025 with 0.017 increased AUROC).ConclusionsThe L/A ratio provides significant adjunctive information to the risk of metabolic syndrome beyond HOMA-IR alone. The L/A ratio could be a good surrogate marker to assess metabolic syndrome.     

Monocyte chemoattractant protein 1-2518 A/G polymorphism and susceptibility to type 2 diabetes in a Chinese population

BackgroundHyperglycemia could accelerate monocyte chemoattractant protein 1 (MCP-1) production in monocytes and vascular endothelial cells. Recently, a genetic polymorphism (–2518 A/G) located in MCP-1 gene promoter has been found that could influence the expression of MCP-1. A large cohort study of Caucasians reported that MCP-1 G–2518 gene variant was negatively correlated with the prevalence of insulin resistance and type 2 diabetes. However, it is unclear whether this polymorphism is associated with type 2 diabetes in Han Chinese.MethodsWe conducted a population-based case–control study of 416 type 2 diabetes cases and 416 controls.ResultsCompared with the wild genotype AA, MCP-1 G–2518 gene variant could significantly decrease the prevalence of type 2 diabetes in Han Chinese (adjusted OR = 0.49, 95% CI 0.32–0.77, P < 0.0001). The results of stratified analyses indicated that a decreased risk of type 2 diabetes related with variant genotypes was evident in younger participants (age ≤ 50) (adjusted OR = 0.35, 95% CI 0.20–0.61, P < 0.0001), and similar results were observed in males (adjusted OR = 0.37, 95% CI 0.21–0.66, P = 0.001) and urban participants (adjusted OR = 0.35, 95% CI 0.21–0.58, P < 0.0001). In addition, a statistically significant difference was observed between MCP-1–2518 A/G polymorphism and waist to hip ratio.ConclusionsOur present pilot study indicated that MCP-1 G–2518 gene variant could significantly decrease the risk of type 2 diabetes in a Chinese population.     

The myeloperoxidase -463G/A polymorphism and coronary artery disease risk: A meta-analysis of 1938 cases and 1990 controls

ObjectivesGenetic polymorphism of human myeloperoxidase (MPO) -463G/A has been implicated to alter the risk of coronary artery disease (CAD), but the results are controversial. To improve the reliability of the conflicting results, we conducted a meta-analysis of studies relating the MPO -463G/A polymorphism with the risk of CAD.Design and methodsTwo investigators independently searched the MEDLINE, EMBASE and Cochrane Library up to June, 2012. Summary odds ratios (OR) and 95% confidence interval (CI) for the MPO -463G/A polymorphism and CAD risk were calculated, and potential sources of heterogeneity and publication bias were explored. Statistical analysis was performed with the software program of Stata 9.0.Results5 case–control studies were finally identified for analyses, involving 1938 cases with CAD and 1990 controls. We found that the MPO -463G/A polymorphism has no significant association with overall CAD risk (G/G vs A/A: OR = 0.595, 95%CI = 0.298–1.188, P = 0.141; G/G vs G/A + A/A: OR = 0.886, 95%CI = 0.779–1.008, P = 0.066; G/G + G/A vs A/A: OR = 0.611, 95%CI = 0.334–1.119, P = 0.111; OR = 0.886, 95%CI = 0.779–1.008, P = 0.066; G vs A: OR = 0.843, 95%CI = 0.675–1.053, P = 0.133). The heterogeneity test showed that there were significant differences between individual studies in additive, recessive and allelic genetic models (P = 0.008, P = 0.021, P = 0.019, respectively); further analyses revealed that age and sex possibly account for the heterogeneity.ConclusionsOur meta-analysis demonstrated the evidence that there was no significant association between the MPO -463G/A polymorphism and the risk of CAD; larger and well-designed multicenter studies are needed to confirm our results.     

Independent risk factors for postoperative pain in need of intervention early after awakening from general anaesthesia

Despite advances in postoperative pain management, the proportion of patients with moderate to severe postoperative pain is still ranging 20–80%. In this retrospective study, we investigated 1736 patients to determine the incidence of postoperative pain in need of intervention (PPINI)defined as numeric rating scale >4 at rest in the post anaesthesia care unit early after awakening from general anaesthesia, and to identify possible risk factors. The proportion of patients with PPINI was 28.5%. On multivariate analysis, younger age (OR = 1.300 [1.007–1.678], p = 0.044), female gender (OR = 1.494 [1.138–1.962], p = 0.004), obesity (OR = 1.683 [1.226–2.310], p = 0.001), use of nitrous oxide (OR = 1.621 [1.110–2.366], p = 0.012), longer duration of surgery (OR = 1.165 [1.050–1.292], p = 0.004), location of surgery (musculoskeletal OR = 2.026 [1.326–3.095], p = 0.001; intraabdominal OR = 1.869 [1.148–3.043], p = 0.012), and ASA-PS I–II (OR = 1.519 [1.131–2.039], P = 0.005) were identified as independent risk factors for PPINI. Patients with PPINI experienced significantly more PONV (10.3% vs. 6.2%, p = 0.003), more psychomotor agitation (5.5% vs. 2.7%, p = 0.004), needed more application of opioid in PACU (62.8% vs. 24.2%, p < 0.001), stayed significantly longer in PACU (89.6 min [70–120] vs. 80 min [60–100], p < 0.001), had a longer median length of hospital stay (6.6 days [4.0–8.8] vs. 6.0 days [3.2–7.8]], p < 0.001), and longer postoperative stay (5.0 days [3.0–6.5] vs. 4.1 days [2.5–5.8], p < 0.001]). Patients with PPINI required more piritramid (8.0 mg [5.0–12.0] vs. 5.0 mg [3.0–7.8], p < 0.001) in PACU than patients without. The identification of patients at high risk for immediate postoperative pain in need of intervention would enable the formation of effective postoperative pain management programs.     

The alarm secretory leukocyte protease inhibitor increases with progressive metabolic dysfunction

BackgroundSecretory leukocyte protease inhibitor (SLPI) is an alarm antiprotease secreted by neutrophils and mucous membranes that potently inhibits the inflammatory cascade; however, the role of SLPI in human disease remains largely unknown. We hypothesized that SLPI is related to chronic low-grade inflammatory diseases, such as metabolic syndrome (MS) or type-2 diabetes (T2DM).MethodsWe examined associations between circulating SLPI (ELISA) and quantitative traits of MS (ATPIII criteria) in 261 Caucasian men with various degrees of metabolic dysfunction. Subjects had neither MS nor T2DM (n = 140), either diagnosis (n = 44) or both diagnoses (n = 77).ResultsCirculating SLPI increased with progressive metabolic dysfunction, with a mean increase of 4.4 ng/ml (95% IC 2.4 to 6.3 ng/ml; p < 0.001) for each unit increase in the criteria used to define MS. Circulating SLPI showed independent associations with uric acid [β = 5.1 (95% CI 3.4 to 6.7), p < 0.00001], serum lipids, pulse pressure and inflammatory markers.ConclusionsCirculating SLPI increases with progressive metabolic dysfunction and is related to metabolic and inflammatory parameters in men.     

Synergistic effects of the polymorphisms in the PAI-1 and IL-6 genes with smoking in determining their associated risk with coronary artery disease

ObjectivesTo assess the relationship between IL-6 and PAI-1 polymorphisms and coronary artery disease (CAD) and to observe the interactions between these polymorphic variants and smoking in the CAD risk.Design and methodThe study population consisted of 178 patients with angiographically documented CAD and 202 blood donors. The analyses of genetic polymorphisms were performed using the PCR-RFLP method.ResultsThe frequency of PAI-1 5G allele was higher in the entire CAD group than in control group (p = 0.04, OR = 1.35). Also the 5G allele carriers (4G5G + 5G5G) were more frequent in patients than in controls (p = 0.03, OR = 1.93). The number of women carrying 5G allele was again significantly higher among patients (OR = 10.95 p = 0.0075). The IL-6 C allele frequency was higher only in the CAD male subgroup (p = 0.035, OR = 1.44). We found synergistic and cumulative effects between specific genotype patterns and smoking in determining the risk of CAD, especially between PAI-1(4G5G + 5G5G)+IL-6(CC) and smoking (SIM = 4.18 and p = 0.0005, OR = 9.20, respectively).ConclusionsThere are synergistic and cumulative effects of 5G allele of PAI-1 polymorphism and C allele of IL-6 polymorphism with smoking in determining their associated risk with CAD.     

Association of high sensitivity C-reactive protein (hsCRP) and tumour necrosis factor-alpha (TNF-alpha) with carotid intimal medial thickness in subjects with different grades of glucose intolerance--the Chennai Urban Rural Epidemiology Study (CURES-31)

ObjectiveTo assess the association of high sensitivity C-Reactive Protein [hsCRP] and Tumour Necrosis Factor-α [TNF-α] with IMT in Asian Indians with different grades of glucose intolerance.Design and methodsSubjects with normal glucose tolerance [NGT](n = 150), impaired glucose tolerance [IGT] (n = 150) and type 2 diabetes (DM) (n = 150) were recruited from the Chennai Urban Rural Epidemiology Study [CURES], in south India. hsCRP was estimated by nephelometry and TNF-α by enzyme linked immunosorbent assay. Carotid IMT was assessed by high resolution B-mode ultrasonography.ResultshsCRP and TNF-α levels were higher in those with DM [p < 0.001] and IGT [p < 0.001] compared to NGT. In linear regression analysis, both hsCRP [p = 0.003] and TNF-α [p =0.001] showed an association with IMT among NGT subjects even after adjusting for age and gender. Among IGT subjects, TNF-α was associated with IMT [p < 0.001], while no association was observed either with hsCRP or TNF-α in diabetic subjects. In NGT subjects, mean IMT was highest in those with high values [III tertile] of both TNF-α and hsCRP [0.83 ± 0.1 mm; p < 0.001] followed by those with high TNF-α + low hsCRP [0.74 ± 0.09 mm; p < 0.001], high hsCRP  low TNF-α [0.67 ± 0.09 mm; p < 0.001], and lowest in those with both low TNF-α and hsCRP [I tertile] [0.63 ± 0.05 mm.ConclusionWe conclude that in Asian Indians 1. Levels of hsCRP and TNF-α increase with increasing severity of glucose intolerance 2. Both hsCRP and TNF-α are associated with IMT in NGT subjects while TNF-α alone is associated with IMT in IGT subjects 3. hsCRP and TNF-α have a cumulative effect on mean IMT values in NGT subjects.     

HOMA-IR and non-HDL-C as predictors of high cholesteryl ester transfer protein activity in patients at risk for type 2 diabetes

Background and aimsMetabolic syndrome (MS) and type 2 diabetes are highly associated with an abnormal lipoprotein profile, which may be generated and accentuated by high cholesteryl ester transfer protein (CETP) activity. Given the difficulty in measuring CETP activity, the aim was to identify simple biochemical predictors of high CETP activity.Design and methodsEighty five subjects at risk for type 2 diabetes were classified according to the presence of MS. Lipoprotein profile, HOMA-IR and endogenous CETP activity were evaluated.ResultsAs expected, MS patients presented higher concentration of glucose, insulin, triglycerides and non-HDL-C and lower HDL-C levels. Moreover, MS patients exhibited increased HOMA-IR and CETP activity. Employing a ROC curve for MS, high CETP activity was defined as > 250% ml^? 1 h^? 1. The predictive variables of high CETP were non-HDL-C ≥ 160 mg/dl (OR = 11.1;95%IC = 3.3–38.2;p < 0.001) and HOMA-IR > 2.1 (OR = 4.4;95%IC = 1.3–14.8;p < 0.05).ConclusionsHigh non-HDL-C and insulin resistance were predictors for increased CETP activity which measurement is not accessible for clinical laboratories.     

Genetic risk factors for renal failure among north Indian ESRD patients

ObjectivesAngiotensin converting enzyme (ACE), G-Protein couple receptor (G-Prot), endothelial nitric oxide synthase (ecNOS), Leptin ? 2548G/A and uncoupling protein (UCP2) are potent regulators of intra renal hemodynamics and may be the causative factors contributing to the deterioration of renal functions. In recent years few studies have been published to show the association of these markers with the end stage renal disease (ESRD). Our study was designed to see the role of different genetic factors individually and synergistically in the progression of renal failure.Design and methodsThe genotypes of these markers were determined by PCR and RFLP. The gene frequencies of ACE, G-protein, ecNOS, Leptin and UCP2 in 184 ESRD patients and 569 healthy controls from North India were compared.ResultsThere was a significant difference between ESRD patients and control groups both in the biochemical parameters and genotype frequencies. The genotype distribution of ACE in patients was significantly different from the controls (p = 0.0001; OR = 9.428; 95% CI = 4.56–19.492). There was no difference observed for the GNB3-825 TT genotype and for ecNOS aa genotype in patient and control groups. The distribution of Leptin ? 2548G/A genotype and UCP2 genotype in patients were significantly different from that of controls (p = 0.0013; OR = 2.804; 95% CI = 1.501–5.237 and p = 0.0001; OR = 8.853; 95% CI = 3.458–22.667 respectively).ConclusionsOur results propose that the ACE-DD, Leptin AA and UCP2-DD genotype may be potential genetic markers for predicting the causation and progression of chronic renal failures.     

Paraoxonase 1 (PON1) as a marker of short term death in breast cancer recurrence

ObjectiveTo relate paraoxonase (PON1) activity to survival time and short term death in breast cancer recurrence.Design and methodsPON1 activity was measured by its rate of hydrolysis of two different substrates, paraoxon (PON) and phenylacetate (ARE) in 50 patients with recurrence of breast cancer. Results were compared between patients surviving more than one year after the analysis (22) and those who died within one year (28).ResultsIn a logistic regression analysis, ARE was negatively associated with early death (OR = 0.10 [0.02–0.58], p = 0.0109). PON did not reach significance (OR = 0.43 [0.17–1.11], p = 0.0826). In a multiple logistic regression analysis model, ARE was independently associated with early death (OR = 0.12 [0.02–0.98], p = 0.0476), besides interval time between diagnosis and recurrence (OR = 0.54 [0.27–1.07], p = 0.0781) and undernutrition (OR = 3.95 [0.81–19.19], p = 0.0883).ConclusionParaoxonase is a potential marker of survival in patients with breast cancer recurrence.     

Predicting successful prosthetic rehabilitation in major lower-limb amputation patients: a 15-year retrospective cohort study

Objective

To determine and compare specific factors that could be associated and predictive with successful prosthetic rehabilitation in major lower-limb amputations.

APOC3 -482C>T polymorphism, circulating apolipoprotein C-III and smoking: interrelation and roles in predicting type-2 diabetes and coronary disease

ObjectivesWe determined the relationship of smoking status on APOC3 ­482C>T polymorphism and apolipoprotein C-III (apoC-III) concentrations and the latter two parameters’ influence on risk of diabetes and coronary heart disease (CHD).Design and methodsPrediction of incident cases was assessed at 5.5 years’ follow-up in unselected 519 individuals of a general population genotyped for ­482C>T polymorphism.ResultsFemale sex and current smoking were significantly associated with low circulating apoC-III in subjects without (p ≤ 0.033) than with abdominal obesity (p = 0.053) or than insulin resistant ­482TT homozygotes (p = 0.034) who had 20–30% higher serum apoC-III. Multi-adjusted serum apoC-III was log-linearly associated with fasting triglycerides. ApoC-III levels determined the development of diabetes [RR 1.56 (95%CI 1.21; 2.01)] and CHD [RR 1.38 (1.10; 1.72) for an increment of 14%], after adjustment for confounders.ConclusionAPOC3 ­482TT genotype is associated with high apoC-III concentrations only in the presence of abdominal obesity or insulin resistance, but not in current smokers who remain lean or insulin-sensitive. Rather than APOC3 ­482C>T polymorphism, circulating apoC-III determines cardiometabolic risk.     

Does clinical incident seriousness and receipt of work-based support influence mood experienced by nurses at work? A behavioural diary study

BackgroundWhile the relationship between general perceptions of the work environment and negative mood is well detailed, little is known about the effect of specific clinical incident characteristics on the mood experienced at work by nurses. This study examines the effect of incident seriousness and receipt of work-based support in the worst event of a shift from managers and colleagues on the Negative and Positive Affect experienced by nurses at work.MethodsWe approached the total cohort of medical and surgical nurses in 4 large district general hospitals in England, 17% volunteered. Some 171 nurses filled end of shift and standard entry (every 90 min) computerised behavioural diaries over three consecutive shifts. The diaries measured Incident Seriousness, Receipt of Managerial and Co-worker Support, Negative Affect and Positive Affect. Results were analysed using multilevel modelling (MLwiN 2.19).FindingsFollowing the worst clinical incident of a shift, nurses reported higher Negative Affect (β = 1.28, [95%CI: 0.12, 2.45], z = 2.17, p < .05) and lower Positive Affect (β = ?2.39, [95%CI: ?3.96, ?0.82], z = 2.99, p < .005) which persisted for the remainder of the shift. Most critically, Negative Affect was more elevated after serious incidents (β = 0.07, [95%CI: 0.04, 0.10], z = 3.5, p < .005). Nurses who reported Receipt of Managerial Support following an incident reported significantly lower levels of Positive Affect compared to those reporting no such contact (β = ?5.30, [95%CI: ?9.51, ?1.09], z = 2.47, p < .05). The interaction between Incident and the Receipt of Work-Based Support on NA was not significant (β = 2.34 [95%CI: ?0.82, 3.95], z = 1.45, p > .05). Receipt of Colleague Support had no relationship with Negative Affect or Positive Affect. Free text reports mainly revealed the negative impact of managerial support, although there were instances of contact with managers which were sought following exposure to difficult clinical situations.DiscussionSerious clinical incidents have enduring effects on Negative Affect and Positive Affect for the remainder of the shift. Nurse Positive Affect was significantly worse following the worst clinical incident of shift when managerial support was received. Further research is required to determine the positive and negative effects of managerial support on the mood experienced by nurses at work.     

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.     

Diagnostic accuracy of biomarkers measured in the hepatic vein and peripheral vein in the prediction of advanced fibrosis in patients with chronic viral hepatitis

ObjectivesThe accuracies of biomarkers checked in the hepatic vein (HV) and peripheral vein (PV) were compared in the prediction of advanced fibrosis (AF) of liver.MethodsPatients with chronic viral hepatitis (n = 101) who underwent hepatic venous pressure gradient, liver biopsy, and paired HV–PV samples (6 biomarkers: hyaluronic acid [HA], haptoglobin, matrix metalloproteinase-2 [MMP2], tissue inhibitor of metalloproteinases-1 [TIMP1], procollagen III N-terminal peptide [PIIINP], and apolipoprotein-A1 [Apo-A1]) were enrolled.ResultsDifferences were displayed between the HV and PV in the predictive logit-models for predicting AF (? 3.13 + 0.017 × MMP2 ? 0.019 × haptoglobin and ? 0.270 + 0.007 × HA ? 0.018 × haptoglobin, respectively). In the area under the receiver operating characteristic curves, PIIINP (0.74/0.68, p = 0.03), MMP2 (0.72/0.63, p = 0.04), HA (0.79/0.76, p = 0.94), Apo-A1 (0.56/0.48, p = 0.73), and predictive logit-model (0.81/0.78, p = 0.68) showed higher diagnostic value in the HV sample.ConclusionsWhile most biomarkers were correlated better with hepatic fibrosis in HV than in PV, individually and in predictive logit-models, they were inadequate to determine the degree of advanced fibrosis.     

Association of MTHFR, MTR, and MTRR polymorphisms with Parkinson's disease among ethnic Chinese in Taiwan

BackgroundInfluence of folate/homocysteine conversion is considered to be important in the pathogenesis of Parkinson's disease (PD). However, association of the folate metabolic pathway gene polymorphisms with PD susceptibility remains unclear.MethodsTo test this possibility in PD, we conducted a hospital-based case-control study constituting 211 patients and 218 age- and sex-matched controls of ethnic Chinese in Taiwan. Genotyping assay was performed to screen for polymorphisms of the methylenetetrahydrofolate reductase (MTHFR C677T), methyltetrahydrofolate-homocysteine methyltransferase (MTR A2756G), and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR A1049G and C1783T) genes and assess the association between these genotype polymorphisms and PD risk using logistic regression analysis.ResultsOf these four non-synonymous polymorphisms, the MTRR 1049GG variant was significantly associated with PD susceptibility (OR = 3.17, 95%CI = 1.08–9.35). Furthermore, we stratified our patients based on the MTHFR 677TT genotype in different strata, a significant association between the joint effect of polymorphisms and PD risk was observed in those patients whose genotypes were MTRR A1049G/MTR A2756G or MTRR C1783T/MTR A2756G (P < 0.05).ConclusionOur findings provide support for the synergistic effects of polymorphisms in the folate metabolic pathway genes in PD susceptibility; the increased PD risk would be more significant in carriers with the polymorphisms of MTHFR, MTR, and MTRR genes.