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1.

BACKGROUND

There is a high and rising rate of immune-mediated diseases in the Western world. Immigrants from South Asia have been reported to be at higher risk upon arrival to the West. We determined the risk of immune-mediated diseases in South Asian and other immigrants to Ontario, Canada, and their Ontario-born children.

METHODS

Population-based cohorts of patients with asthma, type 1 diabetes (T1DM), type 2 diabetes (T2DM), and inflammatory bowel disease (IBD) were derived from health administrative data. We determined the standardized incidence, and the adjusted risk of these diseases in immigrants from South Asia, immigrants from other regions, compared with non-immigrant residents of Ontario. The risk of these diseases in the Ontario-born children of immigrants were compared to the children of non-immigrants.

RESULTS

Compared to non-immigrants, adults from South Asia had higher risk of asthma (IRR 1.56, 95%CI 1.51-1.61) and T2DM (IRR 2.59, 95%CI 2.53-2.65). Adults from South Asia had lower incidence of IBD than non-immigrants (IRR 0.32, 95%CI 0.22-0.49), as did immigrants from other regions (IRR 0.29, 95%CI 0.20-0.42). Compared to non-immigrant children, the incidence of asthma (IRR 0.66, 95%CI 0.62-0.71) and IBD (IRR 0.47, 95%CI 0.33-0.67) was low amongst immigrant children from South Asia. However, the risk in Ontario-born children of South Asian immigrants relative to the children of non-immigrants was higher for asthma (IRR 1.75, 95%CI 1.69-1.81) and less attenuated for IBD (IRR 0.90, 95%CI 0.65-1.22).

CONCLUSION

Early-life environmental exposures may trigger a genetic predisposition to the development of asthma and IBD in South Asian immigrants and their Canada-born children.  相似文献   

2.

Background

The risk of periodontitis (PD) is increased in the patient group of rheumatoid arthritis (RA). RA and PD also shared some pathological mechanism. The aim of this study is to investigate the risk of RA associated with PD exposure.

Methods and Findings

This study identified 3 mutually exclusive cohorts using the 1999–2010 Taiwanese National Health Insurance Research Database (NHIRD) to investigate the association between PD and the risk of incident RA. All patients with PD in 2000 were identified from the database of all enrollees as the PD cohort. From the representative database of 1,000,000 enrollees randomly selected in 2010 (LHID2010), individuals without any periodontal disease (PO) during 1999–2010 were selected as the non-PO cohort. Individuals who were not included in the non-PO cohort and received dental scaling (DS) no more than two times per year during 1999–2010 were selected as the DS cohort from LHID2010. Using cox proportional regression analysis, hazard ratios (HRs) with 95% confidence intervals (Cis) were calculated to quantify the association between PD exposure and RA development. In the three-group comparison using the non-PO cohort as reference, we found that the risk of RA was higher in the PD and DS cohorts (HRs, 1.89 and 1.43; 95% CIs, 1.56–2.29 and 1.09–1.87, respectively). For comparisons between two cohorts, the PD cohort had a higher risk of RA than the non-PO and DS cohorts (HRs, 1.91 and 1.35; 95% CIs, 1.57–2.30 and 1.09–1.67, respectively).

Conclusion

PD was associated with an increased risk of RA development.  相似文献   

3.

Background

Strong and independent associations between plasma concentration of cystatin C and risk of cardiovascular disease (CVD) suggests causal involvement of cystatin C.

Aim

The aim of our study was to assess whether there is a causal relationship between plasma concentration of cystatin C and risk of coronary artery disease (CAD) using a Mendelian Randomization approach.

Methods

We estimated the strength of association of plasma cystatin C on CAD risk and the strength of association of the strongest GWAS derived cystatin C SNP (rs13038305) on plasma cystatin C in the population-based Malmö Diet and Cancer Study (MDC) and thereafter the association between rs13038305 and CAD in the MDC (3200 cases of CAD and 24418 controls) and CARDIOGRAM (22233 cases of CAD and 64762 controls).

Results

Each standard deviation (SD) increment of plasma cystatin C was associated with increased risk of CAD (OR = 1.20, 95% CI 1.07–1.34) after full adjustment. Each copy of the major allele of rs13038305 was associated with 0.34 SD higher plasma concentration of cystatin C (P<1 x 10-35), resulting in a power of >98% to detect a significant relationship between rs13038305 and CAD in MDC and CARDIOGRAM pooled. The odds ratio for CAD (per copy of the major rs13038305 allele) was 1.00 (0.94–1.07); P = 0.92 in MDC, 0.99 (0.96–1.03); P = 0.84 in CARDIOGRAM and 1.00 (0.97–1.03); P = 0.83 in MDC and CARDIOGRAM pooled.

Conclusion

Genetic elevation of plasma cystatin C is not related to altered risk of CAD, suggesting that there is no causal relationship between plasma cystatin C and CAD. Rather, the association between cystatin C and CAD appears to be due to the association of eGFR and CAD.  相似文献   

4.

Background and Objectives

Existing data on pregnancy complications in inflammatory bowel disease (IBD) are inconsistent. To address these inconsistencies, we investigated potential associations between IBD, IBD-related medication use during pregnancy, and pregnancy loss, pre-eclampsia, preterm delivery, Apgar score, and congenital abnormalities.

Methods

We conducted a cohort study in >85,000 Danish National Birth Cohort women who were pregnant in the period 1996-2002 and had information on IBD, IBD-related medication use (systemic or local corticosteroids, 5-aminosalicylates), pregnancy outcomes and potential confounders. We evaluated associations between IBD and adverse pregnancy/birth outcomes using Cox regression and log-linear binomial regression.

Results

IBD was strongly and significantly associated with severe pre-eclampsia, preterm premature rupture of membranes and medically indicated preterm delivery in women using systemic corticosteroids during pregnancy (hazard ratios [HRs] >7). IBD was also associated with premature preterm rupture of membranes in women using local corticosteroid medications (HR 3.30, 95% confidence interval [CI] 1.33-8.20) and with medically indicated preterm delivery (HR 1.91, 95% CI 0.99-3.68) in non-medicated women. Furthermore, IBD was associated with low 5-minute Apgar score in term infants (risk ratio [RR] 2.19, 95% CI 1.03-4.66). Finally, Crohn’s disease (but not ulcerative colitis) was associated with major congenital abnormalities in the offspring (RR 1.85, 95% CI 1.06-3.21). No child with a congenital abnormality born to a woman with IBD was exposed to systemic corticosteroids in utero.

Conclusion

Women with IBD are at increased risk of severe pre-eclampsia, medically indicated preterm delivery, preterm premature rupture of membranes, and delivering infants with low Apgar score and major congenital malformations. These associations are only partly explained by severe disease as reflected by systemic corticosteroid use.  相似文献   

5.

Background

Currently, limited data of the outcome of inflammatory bowel disease (IBD) in patients after solid organ transplantation (SOT) are available. We aimed to analyze effects of SOT on the IBD course in a large IBD patient cohort.

Methods

Clinical data from 1537 IBD patients were analyzed for patients who underwent SOT (n = 31) between July 2002 and May 2014. Sub-analyses included SOT outcome parameters, IBD activity before and after SOT, and efficacy of IBD treatment.

Results

4.74% of patients with ulcerative colitis (UC) and 0.84% of patients with Crohn’s disease (CD) underwent SOT (p = 2.69 x 10−6, UC vs. CD). 77.4% of patients with SOT underwent liver transplantation (LTx) with tacrolimus-based immunosuppressive therapy after SOT. All LTx were due to primary sclerosing cholangitis (PSC) or PSC overlap syndromes. Six patients (19.4%) required renal transplantation and one patient (3.2%) heart transplantation. A survival rate of 83.9% after a median follow-up period of 103 months was observed. Before SOT, 65.0% of patients were in clinical remission and 5 patients received immunosuppressive therapy (16.1%). After SOT, 61.0% of patients were in remission (p = 1.00 vs. before SOT) and 29.0% required IBD-specific immunosuppressive or anti-TNF therapy (p = 0.54 vs. before SOT). 42.9% of patients with worsening of IBD after SOT were at higher risk of needing steroid therapy for increased IBD activity (p = 0.03; relative risk (RR): 10.29; 95% CI 1.26–84.06). Four patients (13.0%) needed anti-TNF therapy after SOT (response rate 75%).

Conclusions

SOT was more common in UC patients due to the higher prevalence of PSC-related liver cirrhosis in UC. Despite mainly tacrolimus-based immunosuppressive regimens, outcome of SOT and IBD was excellent in this cohort. In this SOT cohort, concomitant immunosuppressive therapy due to IBD was well tolerated.  相似文献   

6.

Background

Recently, single nucleotide polymorphisms (SNPs) (DLK-rs10144321, SIX6-rs1254337, MKRN3-rs12148769, LIN28B-rs7759938, and KCNK9-rs1469039) were found to be strongly associated with age at menarche. Recent studies also suggested that age at menarche is a heritable trait and is associated with risks for obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease, and all-cause mortality. Since an association between these five SNPs and premature coronary artery disease (CAD) has never been reported, we investigated whether these SNPs are associated with premature CAD and its severity in a Chinese Han population.

Methods

We enrolled 432 consecutive patients including 198 with premature CAD (<55 years in men and <65 years in women) and 234 controls. All subjects were genotyped for the five SNPs by the PCR-ligase detection reaction method. The associations between these SNPs and premature CAD and its severity were analyzed.

Results

The following genotypes were identified: GG, AG, and AA at rs10144321 and rs12148769; TT, AT, and AA at rs1254337; CC, CT, and TT at rs1469039; and TT and CT at rs7759938. Significant differences in genotype distribution frequencies at rs1254337 were found between controls and patients with premature CAD (P<0.05). No associations were found between the five SNPs and the severity of coronary lesions (all P>0.05). Compared with controls, patients with premature CAD had a higher prevalence of T2DM and dyslipidemia, and the proportion of patients with T2DM rose significantly with an increase in the number of stenosed coronary vessels (all P<0.05). After adjustment for the clinical parameters in multivariable analysis, three factors were identified that significantly increased the risk of premature CAD: the AA genotype at rs1254337 (OR: 2.388, 95% CI: 1.190–4.792, P = 0.014), male gender (OR: 1.565, 95% CI: 1.012–2.420, P = 0.044), and T2DM (OR 2.252, 95% CI: 1.233–4.348, P = 0.015).

Conclusions

Among the five pubertal transition-related gene polymorphisms, we identified an association between rs1254337 and premature CAD in a Chinese Han population.  相似文献   

7.

Background

Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine at multiple phases of atherosclerosis in animals, but human studies are few and inconsistent. The aim of this study is to investigate the association of serum MCP-1with all-cause and cardiovascular disease (CVD) mortality among coronary artery disease (CAD) patients and determine whether this biomarker can add secondary prognostic value to standard risk predictors.

Methods

MCP-1 was measured at baseline in 1411 CAD patients who were 40–85 years of age. Cox proportional hazards regression models were used to estimate the association of MCP-1 levels with death risk.

Results

During a median follow-up of 3.3 years, 117 deaths were recorded, 88 of which were due to CVD. The multivariable-adjusted hazard ratios across tertiles of MCP-1 were 1.51 (95% confidence intervals [CI] 0.89–2.58), 1.00, and 2.11 (95% CI 1.31–3.40) for all-cause mortality, and 1.50 (95% CI 0.80–2.81), 1.00, and 2.21 (95% CI 1.27–3.87) for CVD mortality. The addition of serum MCP-1 to the fully adjusted model increased the C-index by 0.009 (p<0.0001) for all-cause mortality and 0.008 (p<0.0001) for CVD mortality and significantly improved the predictive ability by 12.1% (P = 0.006) on all-cause mortality and 12.6% (P = 0.003) on CVD mortality using the net reclassification improvement method.

Conclusions

Both lower and higher MCP-1 levels are associated with an increased risk of all-cause and CVD mortality among CAD patients. More research is needed to confirm its clinical relevance.  相似文献   

8.

Background

Electronic medical record (EMR) systems are increasingly being adopted to support the delivery of health care in developing countries and their implementation can help to strengthen pathways of care and close gaps in the HIV treatment cascade by improving access to and use of data to inform clinical and public health decision-making.

Methods

This study implemented a novel cloud-based electronic medical record system in an HIV outpatient setting in Western Kenya and evaluated its impact on reducing gaps in the HIV treatment continuum including missing data and patient eligibility for ART. The impact of the system was assessed using a two-sample test of proportions pre- and post-implementation of EMR-based data verification and clinical decision support.

Results

Significant improvements in data quality and provision of clinical care were recorded through implementation of the EMR system, helping to ensure patients who are eligible for HIV treatment receive it early. A total of 2,169 and 764 patient records had missing data pre-implementation and post-implementation of EMR-based data verification and clinical decision support respectively. A total of 1,346 patients were eligible for ART, but not yet started on ART, pre-implementation compared to 270 patients pre-implementation.

Conclusion

EMR-based data verification and clinical decision support can reduce gaps in HIV care, including missing data and eligibility for ART. A cloud-based model of EMR implementation removes the need for local clinic infrastructure and has the potential to enhance data sharing at different levels of health care to inform clinical and public health decision-making. A number of issues, including data management and patient confidentiality, must be considered but significant improvements in data quality and provision of clinical care are recorded through implementation of this EMR model.  相似文献   

9.

Background

Whether diabetic patients without a history of coronary heart disease (CHD) have the same risk of CHD events as non-diabetic patients with a history of CHD remains controversial. This study aimed to determine whether type 2 diabetes mellitus (T2DM) is a coronary heart disease (CHD) equivalent in the need for coronary revascularization procedures (RVs) in the Korean population.

Methodology/Principal Findings

We followed 2,168,698 subjects who had oral anti-diabetic drugs (OADs)-taking T2DM in 2008 and/or CHD in 2007–2008 (i.e., recent CHD). We used systematic datasets from the nationwide claims database of the Health Insurance Review and Assessment service of Korea, which is representative of the whole population of Korea, from January 2007 to December 2012. The primary study endpoint was the development of need for RVs (i.e., incident CHD) after January 2009 among three groups based on their status of T2DM and recent CHD, i.e., T2DM only, recent CHD only, and both T2DM and recent CHD. After adjustment for age and sex, patients with recent CHD only had 2.14 times the risk of incident CHD (95% CI, 2.11–2.18, P<0.001) compared with patients with T2DM only. Patients with both T2DM and recent CHD demonstrated approximately 2-fold increased risk of incident CHD compared with subjects with recent CHD only (95% CI, 1.75-1.82), while 4-fold increased risk compared with subjects with T2DM only (95% CI, 3.71-3.87). The risk of incident CHD also differed according to sex and age.

Conclusions/Significance

This analysis of data from the nationwide claims database revealed that T2DM did not have a recent CHD equivalent risk in the Korean population. These results suggest that an appropriate strategy for the CHD risk stratification in diabetic patients should be adopted to manage this population.  相似文献   

10.

Objectives

Coronary artery disease (CAD) is the most common chronic inflammatory disease worldwide. NF-κB, a central regulator of inflammation, is involved in various inflammatory diseases. The aim of this study was to investigate the association between NFKB1 and NFKBIA polymorphisms and the susceptibility to CAD and their impact on plasma levels of IL-6 in a Chinese Uygur population.

Methods

We genotyped NFKB1-94ins/del ATTG (rs28362491) and NFKBIA3’ UTR A/G (rs696) using TaqMan SNP genotyping assays in 960 Uygur CAD cases and Uygur 1060 CAD-negtive controls. IL-6 plasma levels were measured in 360 stable angina pectoris (SAP) cases and 360 controls using ELISA method.

Results

There was no significant difference in the distribution of the genotypes and alleles of rs696 polymorphism in CAD cases and controls. Significant difference in the frequency of genotypes (P = 0.001) and alleles (P = 0.001) of rs28362491 polymorphism was observed in CAD cases compared to controls. In multivariate logistic regression analysis, SNP rs28362491 was consistently associated with CAD risk in a recessive model after adjustment for cardiovascular risk factors (OR = 1.581, 95% CI 1.222 to 2.046, P<0.001). SAP cases had significantly higher plasma levels of IL-6 compared to controls (P<0.001). General linear model analysis showed rs28362491 was independently associated with increased IL-6 levels by analyses of a recessive model (P<0.001) after adjustment for covariates.

Conclusions

Our study indicates that NFKB1-94 ins/del ATTG polymorphism may play a role in CAD susceptibility in Chinese Uygur population and is functionally associated with IL-6 expression, suggesting a mechanistic link between NFKB1-94 ins/del ATTG polymorphism and CAD susceptibility.  相似文献   

11.
12.
13.

Introduction

Accelerated cardiovascular (CV) disease significantly contributes to increased mortality in rheumatoid arthritis (RA) patients, with a risk comparable to the one observed in patients with type 2 diabetes mellitus (DM). Part of this enhanced risk in RA is attributed to traditional cardiovascular risk factors (CRFs). The aims of this study were to determine how often traditional CRFs are identified and managed by (a) rheumatologists, compared with primary care physicians (PCPs) in RA patients; and (b) PCPs among patients with RA, DM, and the general population (GP).

Methods

A retrospective cohort study compared age/gender/ethnicity-matched patients from three groups: RA, DM, and GP (without RA or DM); n = 251 patients per group. Electronic patient records were reviewed during a continuous 12-month period between June 2007 and April 2011 to assess whether CRFs were identified and managed.

Results

In RA patients, PCPs managed obesity, BP, and lipids significantly more often than did rheumatologists. PCPs managed obesity, BP, and lipids significantly more often in diabetic patients than in the other two groups, and more often in the GP than in RA patients. In patients with elevated BMI, PCPs managed weight in 68% of the DM group, 46% of the GP, and 31% of the RA group (P < 0.0001 for all groups; P = 0.006 between RA and GP groups).

Conclusions

Rheumatologists identify and manage CRFs less frequently than PCPs. PCPs manage CRFs less frequently in RA patients, compared to the GP and DM. Given the increased CV risk associated with RA, physicians need to more aggressively manage CRFs in these patients.  相似文献   

14.
15.

Background

Circulating microRNAs (miRNAs) have been described as potential diagnostic biomarkers in cardiovascular disease and in particular, coronary artery disease (CAD). Few studies were undertaken to perform analyses with regard to risk stratification of future cardiovascular events. miR-126, miR-197 and miR-223 are involved in endovascular inflammation and platelet activation and have been described as biomarkers in the diagnosis of CAD. They were identified in a prospective study in relation to future myocardial infarction.

Objectives

The aim of our study was to further evaluate the prognostic value of these miRNAs in a large prospective cohort of patients with documented CAD.

Methods

Levels of miR-126, miR-197 and miR-223 were evaluated in serum samples of 873 CAD patients with respect to the endpoint cardiovascular death. miRNA quantification was performed using real time polymerase chain reaction (RT-qPCR).

Results

The median follow-up period was 4 years (IQR 2.78–5.04). The median age of all patients was 64 years (IQR 57–69) with 80.2% males. 38.9% of the patients presented with acute coronary syndrome (ACS), 61.1% were diagnosed with stable angina pectoris (SAP). Elevated levels of miRNA-197 and miRNA-223 reliably predicted future cardiovascular death in the overall group (miRNA-197: hazard ratio (HR) 1.77 per one standard deviation (SD) increase (95% confidence interval (CI) 1.20; 2.60), p = 0.004, C-index 0.78; miRNA-223: HR 2.23 per one SD increase (1.20; 4.14), p = 0.011, C-index 0.80). In ACS patients the prognostic power of both miRNAs was even higher (miRNA-197: HR 2.24 per one SD increase (1.25; 4.01), p = 0.006, C-index 0.89); miRA-223: HR 4.94 per one SD increase (1.42; 17.20), p = 0.012, C-index 0.89).

Conclusion

Serum-derived circulating miRNA-197 and miRNA-223 were identified as predictors for cardiovascular death in a large patient cohort with CAD. These results reinforce the assumption that circulating miRNAs are promising biomarkers with prognostic value with respect to future cardiovascular events.  相似文献   

16.

Background

Despite a significant prognostic impact, little is known about disturbances in glucose metabolism among kidney transplant candidates. We assess the prevalence of diabetes mellitus (DM) and prediabetes on kidney transplant waiting list, its underlying pathophysiology and propose an approach for individual risk stratification.

Methods

All patients on active kidney transplant waiting list of a large European university hospital transplant center were metabolically phenotyped.

Results

Of 138 patients, 76 (55%) had disturbances in glucose metabolism. 22% of patients had known DM, 3% were newly diagnosed. 30% were detected to have prediabetes. Insulin sensitivity and-secretion indices allowed for identification of underlying pathophysiology and risk factors. Age independently affected insulin secretion, resulting in a relative risk for prediabetes of 2.95 (95%CI 1.38–4.83) with a cut-off at 48 years. Body mass index independently affected insulin sensitivity as a continuous variable.

Conclusions

The prevalence of DM or prediabetes on kidney transplant waiting list is as high as 55%, with more than one third of patients previously undiagnosed. Oral glucose tolerance test is mandatory to detect all patients at risk. Metabolic phenotyping allows for differentiation of underlying pathophysiology and provides a basis for early individual risk stratification and specific intervention to improve patient and allograft outcome.  相似文献   

17.

Background

Coronary artery disease (CAD) is a complex disease and the leading cause of death in the world. Populations of different ancestry do not always share the same risk markers. Natural selective processes may be the cause of some of the population differences detected for specific risk mutations.

Objective

In this study, 384 single nucleotide polymorphisms (SNPs) located in four genomic regions associated with CAD (1p13, 1q41, 9p21 and 10q11) are analysed in a set of 19 populations from Europe, Middle East and North Africa and also in Asian and African samples from the 1000 Genomes Project. The aim of this survey is to explore for the first time whether the genetic variability in these genomic regions is better explained by demography or by natural selection.

Results

The results indicate significant differences in the structure of genetic variation and in the LD patterns among populations that probably explain the population disparities found in markers of susceptibility to CAD.

Conclusions

The results are consistent with potential signature of positive selection in the 9p21 region and of balancing selection in the 9p21 and 10q11. Specifically, in Europe three CAD risk markers in the 9p21 region (rs9632884, rs1537371 and rs1333042) show consistent signals of positive selection. The results of this study are consistent with a potential selective role of CAD in the configuration of genetic diversity in current human populations.  相似文献   

18.

Purpose

Peripheral arterial disease (PAD) is considered the leading cause of atherosclerotic cardiovascular morbidity. Several risk factors of PAD have been observed in patients with schizophrenia. Therefore, we hypothesize that the incidence of PAD is higher in the schizophrenia population than in the general population.

Methods

The patients in this population-based cohort study were selected from the Taiwanese National Health Insurance Research Database on the basis of the claims data from 2000 to 2011. We compared the incidence of PAD between schizophrenia and nonschizophrenia cohorts. Cox proportional hazard regression models were employed for analyzing the risk of PAD after adjustment for sex, age, and comorbidities.

Results

The adjusted hazard ratio (HR) for PAD in the schizophrenia cohort was 1.26-fold higher than that in the nonschizophrenia cohort. Furthermore, patients with schizophrenia using atypical antipsychotics exhibited a high adjusted HR for PAD.

Conclusion

Compared with the general population, the risk of PAD is higher among patients with schizophrenia. Early diagnosis and intervention can mitigate complications resulting from cardiovascular diseases and lower mortality.  相似文献   

19.

Background

Hyaluronic acid (HA), lubricin, and phospholipid species (PLs) contribute independently or together to the boundary lubrication of articular joints that is provided by synovial fluid (SF). Our study is the first reporting quantitative data about the molecular weight (MW) forms of HA, lubricin, and PLs in SF from cohorts of healthy donors, patients with early (eOA)- or late (lOA)-stage osteoarthritis (OA), and patients with active rheumatoid arthritis (RA).

Methods

We used human SF from unaffected controls, eOA, lOA, and RA. HA and lubricin levels were measured by enzyme-linked immunosorbent assay. PLs was quantified by electrospray ionization tandem mass spectrometry. Fatty acids (FAs) were analyzed by gas chromatography, coupled with mass spectrometry. The MW distribution of HA was determined by agarose gel electrophoresis.

Results

Compared with control SF, the concentrations of HA and lubricin were lower in OA and RA SF, whereas those of PLs were higher in OA and RA SF. Moreover, the MW distribution of HA shifted toward the lower ranges in OA and RA SF. We noted distinct alterations between cohorts in the relative distribution of PLs and the degree of FA saturation and chain lengths of FAs.

Conclusions

The levels, composition, and MW distribution of all currently known lubricants in SF—HA, lubricin, PLs—vary with joint disease and stage of OA. Our study is the first delivering a comprehensive view about all joint lubricants during health and widespread joint diseases. Thus, we provide the framework to develop new optimal compounded lubricants to reduce joint destruction.  相似文献   

20.

Background

Insulin and glucagon-like peptide 1 (GLP-1), converted by proprotein convertase 1 (PC1/3) from proinsulin and proglucagon, are associated with type 2 diabetes (T2DM) and coronary artery disease (CAD). The aim of this study is to investigate the association of PCSK1 gene, which encodes PC1/3, with the risk of CAD in Chinese patients with T2DM.

Methods

We selected and genotyped 5 haplotype-tagging single nucleotide polymorphisms (SNPs) at PCSK1 gene (across 39873bp locus) in a case-control study of Chinese Han population involving 425 diabetic patients (62.1% male, mean age 63.2 years) with CAD as positive cases and 258 diabetic patients (44.2% male, mean age 62.0 years) without CAD as controls.

Results

The allele frequencies at rs3811951 were significantly different between cases and controls (30.7% vs. 37.2%), with the allele G associated with decreased risk for CAD (OR = 0.75, 95% CI = 0.59–0.94, p = 0.013). In recessive inheritance mode, the carriers of GG had a lower risk (OR = 0.50, 95%CI = 0.31–0.82, p = 0.005), even after adjusted for gender, age, BMI and smoking (OR = 0.43, 95%CI = 0.24–0.77, p = 0.004). The carriers of the minor allele A at rs156019 had a higher risk (OR = 1.66, 95%CI = 1.10–2.50, p = 0.016 after adjustment) in dominant inheritance mode. The SNP rs6234 was also significantly associated with CAD risk in women, with the carriers of the minor allele G at rs6234 associated with a reduced CAD risk in recessive inheritance mode (OR = 0.42, 95% CI = 0.18–0.95, p = 0.036 after adjustment).

Conclusions

Our results found that common genetic variants in PCSK1 were associated with CAD in Chinese patients with T2DM.  相似文献   

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