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1.
Wang M Yuan J Li T Liu Y Wu J Di B Chen X Xu X Lu E Li K Liu Y Wu Y Chen X He P Wang Y Liu J 《PloS one》2011,6(2):e16809
Background
To evaluate the risk of the recurrence and the efficiency of the vaccination, we followed-up antibody responses in patients with the 2009 pandemic H1N1 influenza and persons who received the pandemic H1N1 vaccine in Guangzhou China.Methods
We collected serum samples from 129 patients and 86 vaccinated persons at day 0, 15, 30, 180 after the disease onset or the vaccination, respectively. Antibody titers in these serum samples were determined by haemagglutination inhibition (HI) assay using a local isolated virus strain A/Guangdong Liwan/SWL1538/2009(H1N1).Results
HI antibody positive rate of the patients increased significantly from 0% to 60% at day 15 (χ2 = 78, P<0.001) and 100% at day 30 (χ2 = 23, P<0.001), but decreased significantly to 52% at day 180 (χ2 = 38, P<0.001), while that of vaccinated subjects increased from 0% to 78% at day 15 (χ2 = 110, P<0.001) and 81% at day 30 (χ2 = 0.32, P = 0.57), but decreased significantly to 34% at day 180 (χ2 = 39, P<0.001). Geometric mean titers (GMT) of HI antibodies in positive samples from the patients did not change significantly between day 15 and day 30 (T = 0.92, P = 0.36), but it decreased significantly from 80 at day 30 to 52 at day 180 (T = 4.5, P<0.001). GMT of vaccinated persons increased significantly from 100 at day 15 to 193 at day 30 (T = 4.5, P<0.001), but deceased significantly to 74 at day 180 (T = 5.1, P<0.001). Compared to the patients, the vaccinated subjects showed lower seroconversion rate (χ2 = 11, P<0.001; χ2 = 5.9, P = 0.015), but higher GMT (T = 6.0, P<0.001; T = 3.6, P = 0.001) at day 30 and day 180, respectively.Conclusion
Vaccination of 2009 influenza A (H1N1) was effective. However, about half or more recovered patients and vaccinated persons might have lost sufficient immunity against the recurrence of the viral infection after half a year. Vaccination or re-vaccination may be necessary for prevention of the recurrence. 相似文献2.
Purpose
To investigate radiation-induced carotid and cerebral vascular injury and its relationship with radiation-induced temporal lobe necrosis in nasopharyngeal carcinoma (NPC) patients.Methods and Materials
Fifty eight NPC patients with radiation-induced temporal lobe necrosis (TLN) were recruited in the study. Duplex ultrasonography was used to scan bilateral carotid arterials to evaluate the intima-media thickness (IMT) and occurrence of plaque formation. Flow velocities of bilateral middle cerebral arteries (MCAs), internal carotid arteries (ICAs) and basal artery (BA) were estimated through Transcranial Color Doppler (TCD). The results were compared with data from 33 patients who were free from radiation-induced temporal lobe necrosis after radiotherapy and 29 healthy individuals.Results
Significant differences in IMT, occurrence of plaques of ICAs and flow velocities of both MCAs and ICAs were found between patients after radiotherapy and healthy individuals (p<0.05). IMT had positive correlation with post radiation interval (p = 0.049). Compared with results from patients without radiation-induced TLN, the mean IMT was significantly thicker in patients with TLN (p<0.001). Plaques were more common in patients with TLN than patients without TLN (p = 0.038). In addition, flow velocities of MCAs and ICAs in patients with TLN were much faster (p<0.001, p<0.001). Among patients with unilateral TLN, flow velocity of MCAs was significantly different between ipsilateral and contralateral sides to the lesion (p = 0.001).Conclusion
Thickening of IMT, occurrence of plaque formation and hemodynamic abnormality are more common in patients after radiotherapy, especially in those with TLN, compared with healthy individuals. 相似文献3.
Background
The SNP (rs2230500) in PRKCH (the gene encoding protein kinase C η) is associated with ischemic stroke and cerebral hemorrhage in the Chinese population, but the molecular mechanisms are not clear. The aim of the present study is to investigate the association between the SNP and atherosclerosis that is common pathological basis of ischemic stroke and cerebral hemorrhage.Methodology/Principal Findings
We examined the associations of the SNP with carotid intima-media thickness (CIMT), atherosclerosis diagnosed by CIMT, and factors related with inflammation in the Beijing Child Blood Pressure Study. A total of 1190 subjects participated in the follow-up study. The SNP was genotyped by allele-specific real-time PCR assay. The SNP (rs2230500) in PRKCH was significantly associated with CIMT (in far wall of left common carotid arteries, P = 0.016; in far wall of right common carotid arteries, P = 0.012) under a recessive model after adjustment for age, gender, smoking, and hypertension. The SNP was also significantly associated with complement C3 (P = 0.012) under a dominant model after adjustment for age, gender, and high sensitivity C-reactive protein.Conclusions/Significance
Our data provide evidence that the SNP (rs2230500) in PRKCH decreases the risk of CIMT that is a worthwhile predictor of stroke and complement system possibly mediates this process. 相似文献4.
Yang Xiao Aimin Xu Xiaoyan Hui Pengcheng Zhou Xing Li Hui Zhong Weili Tang Gan Huang Zhiguang Zhou 《PloS one》2013,8(6)
Background
The lipocalin family proteins, including lipocalin-2 and retinol-binding protein 4 (RBP4), are adipokines closely associated with obesity-related metabolic disorders. In this study, we evaluated the association of serum lipocalin-2 and RBP4 with intima-media thickness (IMT) and subclinical atherosclerosis in type 2 diabetic patients.Methods and Results
Serum levels of lipocalin-2 and RBP4 were measured in 284 type 2 diabetic patients. Subclinical atherosclerosis was assessed by IMT at carotid, femoral and iliac arteries with ultrasound. Patients with subclinical atherosclerosis showed significantly higher circulating concentrations of lipocalin-2 and RBP4 when compared to those without [112.9 (86.4 to 202.1) µg/L versus 77.2(55.0–150.4) µg/L, 37.1(32.3–40.8) mg/L versus 23.2(20.1–29.2) mg/L, respectively; P = 0.002, P<0.001, respectively]. Moreover, positive correlations were observed between carotid IMT and lipocalin-2 (r = 0.170, P = 0.018) or RBP4 (r = 0.132, P = 0.040), femoral IMT and lipocalin-2 (r = 0.160, P = 0.027), as well as between iliac IMT and RBP4 (r = 0.241, P<0.001). Multiple logistic regression analysis further demonstrated that these two adipokines were independent risk factors for subclinical atherosclerosis in type 2 diabetes.Conclusion
Circulating levels of lipocalin-2 and RBP4 are positively correlated with carotid IMT and subclinical atherosclerosis in type 2 diabetes, which suggests a potential role of these two lipid-binding chaperones in the pathogenesis of vascular complications of diabetes. 相似文献5.
6.
Wang M Zhang R He J Qiu L Li J Wang Y Sun M Yang Y Wang J Yang J Qian J Jin L Ma H Wei Q Zhou X 《PloS one》2012,7(3):e31932
Background
Recent genome-wide association studies (GWAS) have found a single nucleotide polymorphism (SNP, rs2274223 A>G) in PLCE1 to be associated with risk of gastric adenocarcinoma. In the present study, we validated this finding and also explored the risk associated with another unreported potentially functional SNP (rs11187870 G>C) of PLCE1 in a hospital-based case-control study of 1059 patients with pathologically confirmed gastric adenocarcinoma and 1240 frequency-matched healthy controls.Methodology/Principal Findings
We determined genotypes of these two SNPs by the Taqman assay and used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). We found that a significant higher gastric adenocarcinoma risk was associated with rs2274223 variant G allele (adjusted OR = 1.35, 95% CI = 1.14–1.60 for AG+GG vs. AA) and rs11187870 variant C allele (adjusted OR = 1.26, 95% CI = 1.05–1.50 for CG+CC vs. GG). We also found that the number of combined risk alleles (i.e., rs2274223G and rs11187870C) was associated with risk of gastric adenocarcinoma in an allele-dose effect manner (P trend = 0.0002). Stratification analysis indicated that the combined effect of rs2274223G and rs11187870C variant alleles was more evident in subgroups of males, non-smokers, non-drinkers and patients with gastric cardia adenocarcinoma. Further real-time PCR results showed that expression levels of PLCE1 mRNA were significantly lower in tumors than in adjacent noncancerous tissues (0.019±0.002 vs. 0.008±0.001, P<0.05).Conclusions/Significances
Our results further confirmed that genetic variations in PLCE1 may contribute to gastric adenocarcinoma risk in an eastern Chinese population. 相似文献7.
Tanner RM Lynch AI Brophy VH Eckfeldt JH Davis BR Ford CE Boerwinkle E Arnett DK 《PloS one》2011,6(8):e23609
Objectives
MMP-9 and -12 function in tissue remodeling and may play roles in cardiovascular disease (CVD). We assessed associations of four MMP polymorphisms and three antihypertensive drugs with cardiovascular outcomes.Methods
Hypertensives (n = 42,418) from a double-blind, randomized, clinical trial were randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin treatment (mean follow up, 4.9 years). The primary outcome was coronary heart disease (CHD). Secondary outcomes included combined CHD, all CVD outcomes combined, stroke, heart failure (HF), and mortality. Genotype-treatment interactions were tested.Results
There were 38,698 participants genotyped for at least one of the polymorphisms included here. For MMP9 R668Q (rs2274756), lower hazard ratios (HRs) were found for AA subjects for most outcomes when treated with chlorthalidone versus amlodipine (eg., CCHD: GG = 1.00, GA = 1.01, AA = 0.64; P = 0.038). For MMP9 R279Q (rs17576), modest pharmacogenetic findings were observed for combined CHD and the composite CVD outcome. For MMP12 N122S (rs652438), lower HRs were observed for CHD in subjects carrying at least one G allele and being treated with chlorthalidone versus lisinopril (CHD: AA = 1.07, AG = 0.80, GG = 0.49; P = 0.005). In the lisinopril-amlodipine comparison, higher HRs were observed for participants having at least one G allele at the MMP12 N122S locus (CHD: AA = 0.94, AG = 1.19, GG = 1.93; P = 0.041). For MMP12 −82A>G (rs2276109), no pharmacogenetic effect was found for the primary outcome, although lower HRs were observed for AA homozygotes in the chlorthalidone-amlodipine comparison for HF (P = 0.015).Conclusions
We observed interactions between antihypertensive drugs and MMP9 and MMP12 for CHD and composite CVD. The data suggest that these genes may provide useful clinical information with respect to treatment decisions. 相似文献8.
Background
Hepatoma up-regulated protein (HURP) is a component of the chromatin-dependent pathway for spindle assembly. We examined the prognostic predictive value of HURP in human hepatocellular carcinoma (HCC).Methods
HURP expression was evaluated by immunocytochemistry of fine needle aspirated hepatoma cells in 97 HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage A. Subsequently, these patients underwent partial hepatectomy (n = 18) or radiofrequency ablation (n = 79) and were followed for 2 to 35 months. The clinicopathological parameters were submitted for survival analysis.Results
HURP expression in aspirated HCC cells was detected in 19.6% patients. Kaplan-Meier survival analysis showed that positive HURP expression (P = 0.023), cytological grading ≥3 (P = 0.008), AFP ≥35 ng/mL (P = 0.039), bilirubin ≥1.3 mg/dL (P = 0.010), AST ≥50 U/L (P = 0.003) and ALT ≥35 U/L (P = 0.005) were all associated with a shorter disease-free survival. A stepwise multivariate Cox proportional hazard model revealed that positive HURP expression (HR, 2.334; 95% CI, 1.165–4.679, P = 0.017), AST ≥50 U/L (HR, 3.697; 95% CI, 1.868–7.319, p<0.001), cytological grade ≥3 (HR, 4.249; 95% CI, 2.061–8.759, P<0.001) and tumor number >1 (HR, 2.633; 95% CI, 1.212–5.722, P = 0.014) were independent predictors for disease-free survival. By combining the 4 independent predictors, patients with different risk scores (RS) showed distinguishable disease-free survival (RS≤1 vs. RS = 2, P = 0.001; RS = 2 vs. RS = 3, P<0.001). In contrast, the patients cannot be separated into prognosis distinguishable subgroups by using AJCC/UICC TNM staging system.Conclusion
HCC patients with BCLC stage A can be separated into three prognosis-distinguishable groups by use of a risk score that is based upon HURP expression in aspirated HCC cells, ALT, cytological grade and tumor number. 相似文献9.
ML Zhu TY Shi HC Hu J He M Wang L Jin YJ Yang JC Wang MH Sun H Chen KL Zhao Z Zhang HQ Chen JQ Xiang QY Wei 《PloS one》2012,7(7):e41500
Background
Excision repair cross complementing group 5 (ERCC5 or XPG) plays an important role in regulating DNA excision repair; its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity and thus contribute to cancer risk.Methodology/Principal Findings
In a hospital-based case-control study of 1115 esophageal squamous cell carcinoma (ESCC) cases and 1117 cancer-free controls, we genotyped three potentially functional SNPs of ERCC5 (SNPs, rs2296147T>C, rs2094258C>T and rs873601G>A) and estimated crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for their associations with risk of ESCC using unconditional logistic regression models. We also calculated false-positive report probabilities (FPRPs) for significant findings. We found that compared with the TT genotype, ERCC5 rs2296147 C variant genotypes were associated with a significantly lower ESCC risk (CT: adjusted OR = 0.76, 95% CI = 0.63–0.93, CT/CC: adjusted OR = 0.80, 95% CI = 0.67–0.96); however, this risk was not observed for the other two SNPs (rs2094258C>T and rs873601 G>A), nor in further stratification and haplotype analysis.Conclusions/Significances
These findings suggested that ERCC5 polymorphisms may contribute to risk of ESCC in Eastern Chinese populations, but the effect was weak and needs further validation by larger population-based case-control studies. 相似文献10.
Background
Carcinoma of gallbladder (GBC) is an aggressive malignancy. The higher incidence of gallbladder cancer in women has been partly attributed to hormonal factors. Therefore the present study was designed to explore the role of genetic variants in estrogen (ESR1, ESR2) and progesterone (PGR) receptors in conferring risk of gallbladder cancer.Materials and Methods
The present case-control study recruited total of 860 subjects, including 410 GBC patients, 230 gallstone patients and 220 controls. We examined the associations of 6 selected polymorphisms in three genes: ESR1 (rs2234693, rs9340799, rs1801132), ESR2 (rs1271572, rs1256049) and PGR (rs1042838) with GBC risk. Genotyping for all the polymorphisms was done using PCR-RFLP. Multifactor dimensionality reduction and classification and regression tree approaches were combined with logistic regression to discover high-order gene-gene interactions in hormonal pathway.Results
On comparing the genotype frequency distribution in gallstone and GBC patients with that of healthy subjects, the homozygous variant genotypes of ESR1-397TT (rs2234693) polymorphism showed significant risk for developing gallstone [odds ratio: OR = 2.9] and GBC [OR = 1.8] respectively. Detailed haplotypes analysis suggested that ESR1 T rs2234693G rs9340799C rs1801132 have significant association in conferring risk for both gallstones [OR = 2.2] and GBC [OR = 3.0]. However, the variant-containing genotypes (DI+II) of PGR (rs1042838) showed low risk in both GBC [OR = 0.4] and gallstone patients [OR = 0.4].On performing the MDR analysis, ESR1 IVS1-397C>T, ESR1 IVS1-351A>G, and ESR2-789 A>C yielded the highest testing accuracy of 0.634. These results were further supported by the CART analysis which revealed that individuals with the combined genotypes of ESR1-397 CT or TT, ESR1-351 AG or GG and ESR2 -789 AA had the highest risk for GBC [OR = 3.9].Conclusion
Using multi-analytical approaches, our study showed important role of ESR1 IVS1-397C>T, ESR1 IVS1-351A>G, and ESR2-789 A>C variants in GBC susceptibility and the risk appears to be mediated through gallstone dependent pathway. 相似文献11.
Objective
To determine the predictors of the extent of carotid atherosclerosis in patients treated with radiotherapy (RT) for nasopharyngeal carcinoma (NPC).Methods
The present study investigated 129 post-RT NPC patients. Carotid atherosclerotic parameters, such as carotid intima-media thickness, carotid arterial stiffness and carotid plaque burden (plaque score, the presence of plaque and ≥50% stenosis) were assessed using ultrasonography. The association between carotid atherosclerotic parameters and nine potential predictors, including age, gender, post-RT duration, radiation dose, chemotherapy, diabetes mellitus, hypertension, hypercholesterolemia, and smoking, were determined using multiple regression. The cutoff values of age, post-RT duration and number of cardiovascular risk factors for the presence of carotid plaque or ≥50% carotid stenosis were analyzed using receiver operating characteristic (ROC) curve analysis. Multiple testing was corrected using Benjamini-Hochberg false discovery rate.Results
Age, post-RT duration and number of cardiovascular risk factors were significantly associated with carotid plaque burden (corrected P value, Pcor<0.05). Age of 44.5 years (sensitivity = 99.2% and specificity = 50%, Pcor<0.01) and post-RT duration of 8.5 years (sensitivity = 75.7% and specificity = 64.3%, Pcor<0.001) were the cutoff values for detecting carotid plaque, while post-RT duration of 13.5 years (sensitivity = 66.7% and specificity = 71.6%, Pcor<0.001) and 1.5 cardiovascular risk factors (sensitivity = 40.7% and specificity = 84.3%, Pcor<0.05) were the cutoff values for screening ≥50% carotid stenosis.Conclusions
Age, post-RT duration and number of cardiovascular risk factors are significant predictors of carotid atherosclerosis in post-RT NPC patients. Post-RT NPC patients, who are at least 45 years old, with post-RT duration of 9 years or above, and/or have ≥2 cardiovascular risk factors, are more susceptible to carotid atherosclerosis. 相似文献12.
Bastiaan J. van Nierop Hans C. van Assen Elza D. van Deel Leonie B. P. Niesen Dirk J. Duncker Gustav J. Strijkers Klaas Nicolay 《PloS one》2013,8(2)
Background
Left ventricular (LV) and right ventricular (RV) function have an important impact on symptom occurrence, disease progression and exercise tolerance in pressure overload-induced heart failure, but particularly RV functional changes are not well described in the relevant aortic banding mouse model. Therefore, we quantified time-dependent alterations in the ventricular morphology and function in two models of hypertrophy and heart failure and we studied the relationship between RV and LV function during the transition from hypertrophy to heart failure.Methods
MRI was used to quantify RV and LV function and morphology in healthy (n = 4) and sham operated (n = 3) C57BL/6 mice, and animals with a mild (n = 5) and a severe aortic constriction (n = 10).Results
Mice subjected to a mild constriction showed increased LV mass (P<0.01) and depressed LV ejection fraction (EF) (P<0.05) as compared to controls, but had similar RVEF (P>0.05). Animals with a severe constriction progressively developed LV hypertrophy (P<0.001), depressed LVEF (P<0.001), followed by a declining RVEF (P<0.001) and the development of pulmonary remodeling, as compared to controls during a 10-week follow-up. Myocardial strain, as a measure for local cardiac function, decreased in mice with a severe constriction compared to controls (P<0.05).Conclusions
Relevant changes in mouse RV and LV function following an aortic constriction could be quantified using MRI. The well-controlled models described here open opportunities to assess the added value of new MRI techniques for the diagnosis of heart failure and to study the impact of new therapeutic strategies on disease progression and symptom occurrence. 相似文献13.
Background
Recently, several studies have demonstrated that two long non-coding RNAs (lncRNAs), HULC and MALAT1, may participate in hepatocellular carcinoma (HCC) development and progression. However, genetic variations in the two lncRNAs and their associations with HCC susceptibility have not been reported. In this study, we hypothesized that single nucleotide polymorphisms (SNPs) in HULC and MALAT1 may contribute to HCC risk.Methods
We conducted a case-control study and genotyped two SNPs, rs7763881 in HULC and rs619586 in MALAT1, in 1300 HBV positive HCC patients, 1344 HBV persistent carriers and 1344 subjects with HBV natural clearance to test the associations between the two SNPs and susceptibility to HCC and HBV chronic infection.Results
The variant genotypes of rs7763881 were significantly associated with decreased HCC risk in a dominant genetic model [AC/CC vs. AA: adjusted odds ration (OR) = 0.81, 95% confidence intervals (CIs) = 0.68–0.97, P = 0.022]. Furthermore, the variant genotypes of rs619586 was associated with decreased HCC risk with a borderline significance (AG/GG vs. AA: adjusted OR = 0.81, 95% CIs = 0.65–1.01, P = 0.057). However, no significant association was found between the two SNPs and HBV clearance.Conclusions
The variant genotypes of rs7763881 in HULC may contribute to decreased susceptibility to HCC in HBV persistent carriers. 相似文献14.
Objectives
Dendritic cell immunoreceptor (DCIR) has been implicated in development of autoimmune disorders in rodent and DCIR polymorphisms were associated with anti-citrullinated proteins antibodies (ACPA)-negative rheumatoid arthritis (RA) in Swedish Caucasians. This study was undertaken to further investigate whether DCIR polymorphisms are also risk factors for the development of RA in four Asian populations originated from China and Malaysia.Methods
We genotyped two DCIR SNPs rs2377422 and rs10840759 in Han Chinese population (1,193 cases, 1,278 controls), to assess their association with RA. Subsequently, rs2377422 was further genotyped in three independent cohorts of Malaysian-Chinese subjects (MY_Chinese, 254 cases, 206 controls), Malay subjects (MY_ Malay, 515 cases, 986 controls), and Malaysian-Indian subjects (MY_Indian, 378 cases, 285 controls), to seek confirmation of association in various ethnic groups. Meta-analysis was preformed to evaluate the contribution of rs2377422 polymorphisms to the development of ACPA-negative RA in distinct ethnic groups. Finally, we carried out association analysis of rs2377422 polymorphisms with DCIR mRNA expression levels.Results
DCIR rs2377422 was found to be significantly associated with ACPA -negative RA in Han Chinese (OR 1.92, 95% CI 1.27–2.90, P = 0.0020). Meta-analysis confirms DCIR rs2377422 as a risk factor for ACPA-negative RA across distinct ethnic groups (ORoverall = 1.17, 95% CI 1.06–1.30, P = 0.003). The SNP rs2377422 polymorphism showed significant association with DCIR mRNA expression level, i.e. RA-risk CC genotype exhibit a significant increase in the expression of DCIR (P = 0.0023, Kruskal–Wallis).Conclusions
Our data provide evidence for association between DCIR rs2377422 and RA in non-Caucasian populations and confirm the influence of DCIR polymorphisms on RA susceptibility, especially on ACPA-negative RA. 相似文献15.
Wang H Wu M Zhu W Shen J Shi X Yang J Zhao Q Ni C Xu Y Shen H Shen C Gu HF 《PloS one》2010,5(11):e13851
Background
AC3 is one of adenylyl cyclase isoforms involved in cAMP and insulin signaling pathway. Recent reports have demonstrated that the AC3 genetic polymorphisms are associated with obesity in a Swedish population. AC3 knock out mice exhibit obese when they age. These findings suggest that AC3 plays an important role in the regulation of body weight.Methodology/Principal Findings
In the present study, we evaluated the association between the AC3 genetic polymorphisms and obesity in a Han Chinese population. A total of 2580 adults, including 1490 lean (BMI = 18.5–23.9), 677 overweight (BMI 24.0–27.9) and 413 obese (BMI ≥28.0) subjects were genotyped for 5 TagSNPs in the AC3 gene. Single maker association analyses indicated that SNP rs753529 was significantly associated with BMI in obese subjects (P = 0.022, OR = 0.775 95%CI = 0.623–0.963), but not in overweight subjects (P = 0.818). Multiple maker association analyses showed that the haplotype (G-G-G) constructed with SNPs rs1127568, rs7604576 and rs753529 was significantly associated with obesity (P = 0.029). Further genotyping of SNP rs753529 in 816 children, including 361 overweight subjects (BMI>P80) and 455 controls (BMI = P20–50) were performed, and no significant association with BMI was found. All tests were adjusted for age, sex, physical activity index, household income and/or diet expenses.Conclusions
The present study provides replication evidence that the AC3 genetic polymorphisms are associated with decreased risk of obesity among adults but not in children in a Chinese Han population. The data also suggest that the AC3 genetic effects on BMI may have interaction with the factors related to ageing and environment. 相似文献16.
17.
Martinelli N Trabetti E Pinotti M Olivieri O Sandri M Friso S Pizzolo F Bozzini C Caruso PP Cavallari U Cheng S Pignatti PF Bernardi F Corrocher R Girelli D 《PloS one》2008,3(2):e1523
Background
Relative little attention has been devoted until now to the combined effects of gene polymorphisms of the hemostatic pathway as risk factors for Myocardial Infarction (MI), the main thrombotic complication of Coronary Artery Disease (CAD). The aim of this study was to evaluate the combined effect of ten common prothrombotic polymorphisms as a determinant of MI.Methodology/Principal Findings
We studied a total of 804 subjects, 489 of whom with angiographically proven severe CAD, with or without MI (n = 307; n = 182; respectively). An additive model considering ten common polymorphisms [Prothrombin 20210G>A, PAI-1 4G/5G, Fibrinogen β -455G>A, FV Leiden and “R2”, FVII -402G>A and -323 del/ins, Platelet ADP Receptor P2Y12 -744T>C, Platelet Glycoproteins Ia (873G>A), and IIIa (1565T>C)] was tested. The prevalence of MI increased linearly with an increasing number of unfavorable alleles (χ2 for trend = 10.68; P = 0.001). In a multiple logistic regression model, the number of unfavorable alleles remained significantly associated with MI after adjustment for classical risk factors. As compared to subjects with 3-7 alleles, those with few (≤2) alleles had a decreased MI risk (OR 0.34, 95%CIs 0.13–0.93), while those with more (≥8) alleles had an increased MI risk (OR 2.49, 95%CIs 1.03–6.01). The number of procoagulant alleles correlated directly (r = 0.49, P = 0.006) with endogenous thrombin potential.Conclusions
The combination of prothrombotic polymorphisms may help to predict MI in patients with advanced CAD. 相似文献18.
Mahajan A Tabassum R Chavali S Dwivedi OP Chauhan G Ghosh S Tandon N Bharadwaj D 《PloS one》2011,6(9):e24645
Background
High sensitivity C-reactive protein (hsCRP) levels are shown to be influenced by genetic variants in Europeans; however, little is explored in Indian population.Methods
Herein, we comprehensively evaluated association of all previously reported genetic determinants of hsCRP levels, including 18 cis (proximal to CRP gene) and 73 trans-acting (distal to CRP gene) variants in 4,200 North Indians of Indo-European ethnicity. First, we evaluated association of 91 variants from 12 candidate loci with hsCRP levels in 2,115 North Indians (1,042 non-diabetic subjects and 1,073 patients with type 2 diabetes). Then, cis and trans-acting variants contributing maximally to hsCRP level variation were further replicated in an independent 2,085 North Indians (1,047 patients with type 2 diabetes and 1,038 non-diabetic subjects).Results
We found association of 12 variants from CRP, LEPR, IL1A, IL6, and IL6R with hsCRP levels in non-diabetic subjects. However, only rs3093059-CRP [β = 0.33, P = 9.6×10−5] and the haplotype harboring rs3093059 risk allele [β = 0.32 µg/mL, P = 1.4×10−4/Pperm = 9.0×10−4] retained significance after correcting for multiple testing. The cis-acting variant rs3093059-CRP had maximum contribution to the variance in hsCRP levels (1.14%). Among, trans-acting variants, rs1892534-LEPR was observed to contribute maximally to hsCRP level variance (0.59%). Associations of rs3093059-CRP and rs1892534-LEPR were confirmed by replication and attained higher significance after meta-analysis [βmeta = 0.26/0.22; Pmeta = 4.3×10−7/7.4×10−3 and βmeta = −0.15/−0.12; Pmeta = 2.0×10−6/1.6×10−6 for rs3093059 and rs1892534, respectively in non-diabetic subjects and all subjects taken together].Conclusion
In conclusion, we identified rs3093059 in CRP and rs1892534 in LEPR as major cis and trans-acting contributor respectively, to the variance in hsCRP levels in North Indian population. 相似文献19.
Background
Potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) is thought to be an important candidate gene of diabetes. Several single nucleotide polymorphisms (SNPs) in a 40-kb linkage disequilibrium (LD) block in its intron 15 have been identified to be associated with diabetes in East Asian populations in recent genome-wide association studies. The aim of this study was to investigate whether KCNQ1 polymorphisms influence the levels of the metabolic phenotypes in general Chinese populations.Methodology/Principal Findings
We investigated the associations of two SNPs (rs2237892 and rs2237895) in the aforementioned 40-kb LD block, a missense variant rs12720449 (P448R) in exon 10, and a synonymous variant rs1057128 (S546S) in exon 13 with metabolic phenotypes in a Uyghur population (n = 478) and replicated these associations in a Han population (n = 2,485). We found that rs2237892-T allele was significantly associated with decreased triglyceride levels (pcombined = 0.001). The minor G allele of the rs12720449, with sharp difference of the allelic frequency between European and East Asian populations (0.2% versus 14%, respectively), was associated with a lower triglyceride levels than G allele in Uyghur subjects (p = 0.004), in Han subjects (p = 0.052), and in subjects of meta-analysis (pcombined = 0.001). Moreover, the minor A allele of the rs1057128 was also associated with decreased triglyceride levels in meta-analysis (pcombined = 0.010).Conclusions
To the best of our knowledge, this is the first report associating a missense mutation of KCNQ1, rs12720449, with triglyceride levels. Rs2237892, representing the 40-kb LD block, is also associated with triglyceride levels in Han population. Further studies are required to replicate these findings in other East Asian populations. 相似文献20.
La D Czarnecki C El-Gabalawy H Kumar A Meyers AF Bastien N Simonsen JN Plummer FA Luo M 《PloS one》2011,6(12):e29200