Association of PDE4D and IL-1 gene polymorphism with ischemic stroke in a Han Chinese population

Background

The single-nucleotide polymorphisms (SNPs) of the phosphodiesterase 4D (PDE4D) and interleukin-1 (IL-1) genes are associated with increased risk for the development of ischemic stroke (IS) in whites. However, little is known about whether this association could also occur in Han Chinese.

Method

A total of 371 patients with IS and unrelated healthy controls were recruited and the SNPs of the PDE4D (83T/C), (87T/C), IL-1 (−889C/T) and IL-1 (−511C/T) were characterized, respectively, by polymerase chain reactions-restriction fragment length polymorphism (PCR-RFLP). The genotype and allele frequencies of these SNPs in this population were statistically analyzed.

Results

The genotype and allele frequencies of the PDE4D (87T/C) and IL-1 (−511C/T) were similar between IS patients and controls. In contrast, the frequencies of CC genotype and C allele of the PDE4D (83T/C) and the T allele frequency of IL-1 (−889C/T) in IS patients were significantly higher than that in healthy controls (p = 0.001, p = 0.003 and p = 0.02, respectively), independent of the conventional risk factors. The values of odds ratio (OR) reached at OR = 1.603; 95%CI = 1.032-2.489; p = 0.036 for the CC genotype of the PDE4D (83T/C) and OR = 1.913; 95%CI = 1.621-2.375; p = 0.034 for the TT genotype of the IL-1 (−889C/T), respectively.

Conclusions

the SNPs of the PDE4D (83T/C) and IL-1 (−889C/T) were associated with increased risk for the development of IS in Northern Han Chinese.     

Interleukin-18 −137 G/C and −607 C/A polymorphisms and Alzheimer’s disease risk: a meta-analysis

The ?137 G/C and ?607 C/A polymorphisms in interleukin-18 (IL-18) gene have been reported to be associated with Alzheimer’s disease (AD) risk, but the results are inconclusive. Considering a single study may lack the power to provide reliable conclusion, we performed a meta-analysis to investigate the association between the IL-18 ?137 G/C and ?607 C/A polymorphisms and AD susceptibility. A comprehensive literature search of PubMed, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases were conducted before September 1, 2015. The pooled odds ratio (OR) with 95 % confidence intervals (CIs) were calculated. Five eligible studies with a total of 1536 subjects were finally included in this meta-analysis. For the IL-18 ?137 G/C polymorphism, a significantly decreased risk was detected in patients carrying the C allele of ?137 G/C in all study subjects in allele model (C vs. G: OR = 0.816, 95 % CI = 0.680–0.980, p = 0.029). Moreover, stratification by ethnicity indicated markedly association between the ?137 G/C C allele and AD risk in Asians. For the IL-18 ?607 C/A polymorphism, a significantly decreased risk was found in patients carrying the A allele of ?607 C/A in all study subjects in dominant model (AA + CA vs. CC: OR = 0.696, 95 % CI = 0.529–0.915, p = 0.010). However, the results suggested no significant association between the ?607 C/A polymorphism and AD susceptibility when stratified by ethnicity. Our present meta-analysis suggests that the C allele carrier of IL-18 ?137 G/C was associated with decreased risk for AD in Asians. Further well-designed case–control studies with larger sample size and more ethnic groups are needed to confirm these conclusions.     

白介素-18基因启动子-607C／A多态性与缺血性脑卒中的相关性

目的：阐明白介素-18（IL-18）与缺血性脑卒中（IS）的相关性。方法：采用病例对照研究方法,对IS病例组423例和对照组384名（两组研究对象年龄、性别匹配,均为中国汉族人群）应用聚合酶链反应技术（PCR）及凝胶电泳技术进行IL-18基因启动子-607C／A（rs1946518）分析。用Logistic回归分析去除混杂因素的影响,分析其基因型、等位基因型与缺血性脑卒中发病的相关性。结果：-607C等位基因型与IS发病有相关性,是IS重要的危险因素（OR=I．358,P=0．002）。结论：中国汉族人群中,IL-18基因启动子的多态性可能与IS的发病有关,等位基因型-607C可能增加IS的发病风险。     

白介素-18基因启动子多态性与阿尔茨海默病的关联分析

目的 探讨IL-18基因启动子区位点单核苷酸多态性与散发性阿尔茨海默病(SAD)的相关关系.方法 采用病例对照的研究方法,共入选SAD患者109例和同期年龄、性别完全匹配的对照组109例.应用序列特异性引物-聚合酶链反应技术检测两组对象IL-18基囚启动子-607C/A位点单核苷酸多态性.结果 IL-18基囚启动子-607C/A位点等位基因和基因型分布在SAD组和对照组间比较差异有统计学意义(P=0.021,P=0.041).SAD组-607CC基因型分布频率明显高于对照组,比较差异有统计学意义(x2=4.109,P=0.043),携带-607CC基因型的人群患SAD的风险是非携带人群的1.90倍(OR=1.90,95%CI:1.017～3.550).结论 SAD与IL-18基因启动子-607C/A位点单核苷酸多态性相关,其中-607CC基因型的人群发生SAD的风险较其他基因型人群的风险高.     

Association between adiponectin gene polymorphisms and coronary artery disease across different populations

Objective

Many studies have suggested that adiponectin gene might be involved in the development of coronary artery disease (CAD). However, the results have been inconsistent. In this study, the authors performed a meta-analysis to assess the associations of + 45T/G, + 276G/T and − 11377C/G polymorphisms in adiponectin gene with CAD susceptibility.

Methods

Published literature from PubMed and EMBASE databases were searched. Pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated using fixed- or random-effects model.

Results

Sixteen studies (4394 cases / 8187 controls) for + 45T/G polymorphism, fifteen studies (3569 cases / 7463 controls) for + 276G/T polymorphism, and thirteen studies (3531 cases / 7072 controls) for − 11377C/G polymorphism were included in the meta-analysis. The overall results showed that there was a statistically significant association between − 11377C/G polymorphism and CAD (G vs. C: OR = 1.15, 95%CI 1.07-1.24).Similar results were observed among European (G vs. C: OR = 1.11, 95%CI 1.02-1.20) and East Asian populations (G vs. C: OR = 1.27, 95%CI 1.11-1.45). However, no significant association was found for + 45T/G or + 276G/T polymorphism with CAD susceptibility.

Conclusions

The meta-analysis indicated the significant association of − 11377C/G polymorphism, but not + 45T/G or + 276G/T polymorphism, with CAD susceptibility. However, large-scale studies with the consideration of gene-gene and gene-environment interactions should be conducted to investigate the associations in future.     

Association between PAI-1 4G/5G Polymorphisms and osteonecrosis of femoral head: A Meta-analysis

Background

The polymorphism of the plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene has been correlated with susceptibility to osteonecrosis of the femoral head (ONFH), but study results are controversial. The aim of this study was to derive a more precise estimation of the relationship between the PAI-1 4G/5G Gene polymorphism and ONFH by performing a meta-analysis.

Methods

The meta-analysis was based on five eligible case-control studies involving 419 cases and 969 controls and summarized data indicating the association between PAI-1 polymorphism and risk of osteonecrosis of the femoral head. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to assess the strength of this association in the random-effects model or fixed-effects model.

Results

A significant association between PAI-1 4G/5G polymorphism and ONFH susceptibility was observed for 4G4G + 4G5G vs. 5G5G (OR = 1.766, 95% CI 1.279–2.437, P = 0.001), 4G/4G vs. 4G/5G + 5G/5G (OR = 2.050, 95% CI 1.581–2.657, P = 0.000), 4G/4G vs. 5G/5G (OR = 2.553, 95% CI 1.345–4.846, P = 0.004), and 4G vs. 5G (OR = 1.758, 95% CI 1.236–2.500, P = 0.002). No significant association between PAI-1 4G/5G polymorphism and ONFH susceptibility was observed for 4G/5G vs. 5G/5G (OR = 1.327, 95% CI 0.939–1.877, P = 0.109).

Conclusions

This meta-analysis suggested that 4G/5G polymorphism of the PAI-1 gene was a risk factor for ONFH. This study also suggests that the PAI-1 4G4G genotype may indicate a risk for ONFH.     

Influence of the β-fibrinogen-455G/A polymorphism on development of ischemic stroke and coronary heart disease

Background

Ischemic stroke (IS) and coronary heart disease (CHD) are two vascular disorders that are a common cause of death worldwide. Several studies have assessed the association of the β-fibrinogen-455G/A (FGB-455G/A) polymorphism and risk of IS and CHD, but the results are still inconsistent. Our study aimed to investigate whether the FGB-455G/A polymorphism was associated with susceptibility to IS and CHD by using meta-analysis.

Methods

Relevant studies were identified from PubMed, Embase and four Chinese database up to July 2013.Data were analyzed and processed by Stata 11.2. A pooled OR with 95% CI was calculated to estimate the strength of the genetic association. Cumulative meta-analysis was performed to assess the tendency of pooled OR over time.

Results

45 studies based on a total of 7238 cases and 7395 controls were included in our meta-analysis. The results indicated that the FGB-455G/A polymorphism is associated with the risk of IS when compared with the dominant model (OR = 1.518, 95%CI = 1.279-1.802 for AA + GA vs. GG). In the subgroup analysis by ethnicity, significantly elevated risks were associated with the A allele in Asians (OR = 1.700, 95%CI = 1.417-2.040), but not in Caucasians (OR = 0.942, 95%CI = 0.813-1.091). Both the hypertension and non-hypertension subgroups reached significant results, but no significance was found when stratified according to sex or subtype of IS. Results indicate that the FGB-455G/A polymorphism is associated with CHD (OR = 1.802, 95%CI = 1.445-2.246).

Conclusion

Our meta-analysis suggests that the FGB-455G/A polymorphism contributes to susceptibility to IS and CHD.     

A case-control study provides evidence of association for a common SNP rs974819 in PDGFD to coronary heart disease and suggests a sex-dependent effect

Introduction

Peden et al. have revealed a significant association between four new risk loci and coronary heart disease (CHD) in Europeans and South Asians. The goal of this study is to evaluate the contribution of these genetic loci to CHD risk in Han Chinese.

Methods

We recruited 161 CHD patients and 112 controls proved by angiography originated from Ningbo in the Eastern China, and performed a case-control association study of the four significant SNPs.

Results

Among the four tested SNPs, we found a significant association of rs974819 in PDGFD gene with CHD (allele p = 0.04; OR = 1.45, 95% CI = 1.02 - 2.08) and the allele A/G of rs974819 shows significant difference in females (allele p = 0.04; OR = 1.83, 95% CI = 1.01 - 3.31). A further meta-analysis showed that rs974819 of PDGFD gene was significantly associated with an increasing risk of CHD (OR = 1.08, 95% CI = 1.05 - 1.11) in both Europeans and South Asians including Han Chinese.

Conclusions

Our findings suggests that rs974819 of PDGFD is also a CHD risk factor in Han Chinese. In addition, it presents a sex-dependent genetic effect.     

Ischemic stroke susceptibility gene in a Northern Han Chinese population

Interleukin-18 gene promoter polymorphisms are potential risk factors for ischemic cerebrovascular disease, and the –607C allele may increase ischemic stroke risk in the Han Chinese population. In the present study, we recruited 291 patients with ischemic cerebrovascular disease from the Affiliated Hospital of Qingdao University Medical College, China, and 226 healthy controls. Both patients and controls were from the Han population in northern China. Immunoresonance scattering assays detected increased serum amyloid A protein, C-reactive protein, and interleukin-18 levels in ischemic cerebrovascular disease patients compared with healthy controls. Analysis of the –607C/A （rs1946518） polymorphism in the interleukin-18 gene promoter showed ischemic cerebrovascular disease patients exhibited increased frequencies of the CC genotype and C alleles than healthy controls. Genotype and allele frequencies of the interleukin-18 –137G/C （rs187238） polymorphism and the –13T/C （rs11024595） polymorphism in the 5＇-flanking region of serum amyloid A, showed no significant difference between the two groups. Multivariate logistic regression analysis on the interleukin-18 promoter A/C genetic locus, for correction of age, gender, history of smoking, hypertension, diabetes mellitus, hypercholesteremia, and an ischemic stroke family history, showed ischemic cerebrovascular disease risk in individuals without the A allele （C homozygotes） was 2.2-fold greater than in A allele carriers. Overall, our findings suggest that the –13T/C （rs11024595） polymorphism in the 5′-flanking region of serum amyloid A has no correlation with ischemic cerebrovascular disease, but the C allele of the –607C/A （rs1946518） polymorphism in the interleukin-18 promoter is a high-risk factor for ischemic cerebrovascular disease in the Han population of northern China. In addition, the A allele is likely a protective gene for ischemic cerebrovascular disease.     

Genetic variants of D2 but not D3 or D4 dopamine receptor gene are associated with rapid onset and poor prognosis of methamphetamine psychosis

D2-like receptors are key targets for methamphetamine in the CNS, and their activation is an initial and indispensable effect in the induction of dependence and psychosis. It is possible that genetic variants of D2-like receptors may affect individual susceptibility to methamphetamine dependence and psychosis. To test this hypothesis, 6 putatively functional polymorphisms of D2-like receptors, −141C Ins/Del, Ser311Cys and TaqIA of the DRD2 gene, Ser9Gly of the DRD3 gene, and −521C>T and a variable number of tandem repeats in exon 3 of the DRD4 gene, were analyzed in 202 patients with methamphetamine dependence and/or psychosis and 243 healthy controls in a Japanese population. No polymorphism examined showed significant association with methamphetamine dependence, but two polymorphisms of DRD2 were associated with the clinical course and prognosis of methamphetamine psychosis. The A1/A1 homozygote of DRD2 was a negative risk factor for a poorer prognosis of psychosis that continues for more than 1 month after the discontinuance of methamphetamine abuse and the beginning of treatment with neuroleptics (p = 0.04, odds ratio (OR) = 0.42, 95% CI; 0.27–0.65) and the complication of spontaneous relapse of methamphetamine psychosis after remission (p = 0.014, OR = 0.34, 95% CI; 0.22–0.54). The genotype of −141C Del positive (Del/Del and Del/Ins) was at risk for rapid onset of methamphetamine psychosis that develops into a psychotic state within 3 years after initiation of methamphetamine abuse (p = 0.00037, OR = 3.62, 95% CI 2.48–5.28). These findings revealed that genetic variants of DRD2, but not DRD3 or DRD4, confer individual risks for rapid onset, prolonged duration, and spontaneous relapse of methamphetamine psychosis.     

Synergistic association of DNA repair relevant gene polymorphisms with the risk of coronary artery disease in northeastern Han Chinese

Evidence is mounting suggesting that DNA damage is implicated in the development and progression of atherosclerosis. To yield more information, we focused on six well-characterized polymorphisms from four DNA repair-relevant candidate genes, viz. XRCC1 (rs1799782 and rs25487), XRCC3 (rs861539), MTHFR (rs1801133 and rs4846049), and NQO1 (rs1800566), to identify and characterize their potential gene-to-gene interactions in susceptibility to coronary artery disease (CAD) in Han Chinese. This was a hospital-based case-control study involving 1142 patients diagnosed with CAD and 1106 age- and gender-matched controls. All participants were angiographically confirmed. Risk estimates were expressed as odds ratio (OR) and 95% confidence interval (95% CI). All six examined polymorphisms met Hardy-Weinberg equilibrium. Overall there were significant differences in the genotype/allele distributions of MTHFR gene rs1801133 and rs4846049 (both P ≤ 0.005), and in the genotype distributions of XRCC1 gene rs1799782 (P = 0.002) between patients and controls. The adjusted risk of having CAD was more evident for rs1799782 (OR = 1.53; 95% CI: 1.16-2.02; P = 0.003), rs1801133 (OR = 1.54; 95% CI: 1.22-1.94; P < 0.001), and rs4846049 (OR = 1.74; 95% CI: 1.13-2.69; P = 0.013) under the recessive model. Interaction analyses indicated that the overall best multifactor dimensionality reduction (MDR) model included rs4846049, rs1801133, and rs1799782, and this model had a maximal testing accuracy of 0.6885 and a cross-validation consistency of 10 out of 10 (P = 0.0030). Further interaction entropy graph bore out the validity of this MDR model. Taken together, our findings demonstrate a contributory role of genetic defects in XRCC1 and MTHFR genes, both individually and interactively, in the development of CAD in Han Chinese.     

Role of serotonergic-related systems in suicidal behavior: Data from a case-control association study

Objective

To investigate whether functional polymorphisms directly (HTR2A and SLC6A4 genes) or indirectly (IL-1 gene complex, APOE and ACE genes) related with serotonergic neurotransmission were associated with suicidal behavior.

Subjects and methods

227 suicide attempters, 686 non-suicidal psychiatric patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods.

Results

There were no differences in genotype frequencies between the three groups. The −1438A/G [χ² (df) = 9.80 (2), uncorrected p = 0.007] and IL-1α −889C/T [χ² (df) = 8.76 (2), uncorrected p = 0.013] genotype frequencies between impulsive and planned suicide attempts trended toward being different (not significant after Bonferroni correction). Suicide attempts were more often impulsive in the presence of −1438G/G or IL-1α −889C/T or C/C genotypes. There was interaction between the polymorphism 5-HTTLPR and age [LRT (df) = 6.84 (2), p = 0.033] and between the polymorphisms APOE and IL-1RA (86 bp)_n [LRT (df) = 12.21 (4), p = 0.016] in relation to suicide attempt lethality.

Conclusion

These findings further evidence the complexity of the association between genetics and suicidal behavior, the need to study homogenous forms of the behavior and the relevance of impulsive and aggressive traits as endophenotypes for suicidal behavior.     

Risk factors for hospital-sssociated venous thromboembolism in the neonatal intensive care unit

Objective

To determine hospital-associated venous thromboembolism (HA-VTE) risk factors in critically ill neonates.

Methods

We conducted a case-control study in the neonatal intensive care unit (NICU) of All Children’s Hospital Johns Hopkins Medicine (St. Petersburg, FL), from January 1, 2006 - April 10, 2013. We identified HA-VTE cases using electronic health record. Four NICU controls were randomly selected for each HA-VTE case. Associations between putative risk factors and HA-VTE were estimated using odds ratios (ORs) and ninety-five percent confidence intervals (95%CIs) from univariate and multivariate regression analyses.

Results

Twenty-three HA-VTE cases and 92 controls were included. The annual HA-VTE incidence was approximately 1.4 HA-VTE cases per 1,000 NICU admissions. In univariate analyses, mechanical ventilation (OR = 7.27, 95%CI = 2.02-26.17, P = 0.002), central venous catheter (CVC; OR = 52.95, 95%CI = 6.80-412.71, P < 0.001), infection (OR = 7.24, 95%CI = 2.66-19.72, P < 0.001), major surgery (OR = 5.60, 95%CI = 1.82-17.22, P = 0.003) and length of stay ≥ 15 days (OR = 6.67, 95%CI = 1.85-23.99, P = 0.004) were associated with HA-VTE. Only CVC (OR = 29.04, 95%CI = 3.18-265.26, P = 0.003) remained an independent risk factor in the multivariate analysis. Based on this result, the estimated risk of HA-VTE in NICU patients with a CVC was 0.9%.

Conclusion

This study identifies CVC as an independent risk factor for HA-VTE in critically ill neonates. However, the level of risk associated with CVC is below the conventional threshold for primary anticoagulation thromboprophylaxis. Larger studies are needed to substantiate these findings and identify novel putative risk factors to further distinguish NICU patients at highest HA-VTE risk.     

Genetic polymorphisms in the dopamine-2 receptor (DRD2), dopamine-3 receptor (DRD3), and dopamine transporter (SLC6A3) genes in schizophrenia: Data from an association study

Objective

To investigate the association between dopaminergic polymorphisms [DRD2 −141C Ins/Del, DRD3 Ser9Gly, and SLC6A3 VNTR] and schizophrenia.

Methods

Two hundred and eighty-eight outpatients with schizophrenia (DSM-IV criteria) [mean age (SD) = 36.4 (12.4), 60.1% males] and 421 unrelated healthy controls [mean age (SD) = 40.6 (11.3), 51.3% males] from a homogeneous Spanish Caucasian population were genotyped using standard methods.

Results

There was a significant difference in genotype distribution for the DRD2 −141C Ins/Del polymorphism [(χ² (2) = 12.35, corrected p = 0.012]. The − 141C Del allele was more common in patients than in controls [0.19 vs. 0.13; χ² (1) = 9.14, corrected p = 0.018, OR (95% CI) = 1.57 (1.17–2.10)]. Genotype and allele distributions for DRD3 Ser9Gly and SLC6A3 VNTR polymorphisms were similar in both groups. However, there was tentative evidence of an interaction effect between DRD3 Ser9Gly and SLC6A3 VNTR [Wald = 9.56 (4), p = 0.049]. Compared to the SLC6A3 10/10 genotype category, the risk of schizophrenia was halved among those with 9/10 [OR = 0.51 (95% CI = 0.30–0.89), p = 0.017]. This protective effect was only present in combination with DRD3 Ser/Ser genotype because of the significant interaction between 9/10 and both Ser/Gly [OR = 2.45 (95% CI = 1.16–5.17), p = 0.019] and Gly/Gly [OR = 3.80 (95% CI = 1.24–11.63), p = 0.019].

Conclusions

This study provides evidence that a genetic variant in the DRD2 gene and possible interaction between DRD3 and SLC6A3 genes are associated with schizophrenia. These findings warrant examination in replication studies.     

The association between non-motor symptoms in Parkinson's disease and age at onset

Objective

Age at onset is likely to be related to a wide range of problems in Parkinson's disease (PD), including cardinal motor features, motor complications and non-motor symptoms (NMS). This study investigated the effect of the age at onset on NMS.

Methods

Two hundred and thirty patients were examined and classified into one of three groups based on age at onset: early onset PD (EOPD) group (<45 years), middle-age onset group (45–64 years) and old-age onset group (≥65 years). The trends relating to NMS were compared across the three groups. The EOPD and old-age onset groups were separately studied to determine their association to the appearance of non-motor features using logistic regression analysis.

Results

There were upward trends in the occurrence of dribbling (P = 0.009; all P values are stated for trend), impaired taste/smelling (P = 0.016), constipation (P = 0.006), urinary urgency (P = 0.002), nocturia (P = 0.018), hallucinations (P = 0.016) and acting out during dreams (P = 0.011) with the increase of age at onset. Older age at onset is an independent risk factor for dementia (OR = 8.42, CI 3.16–22.44), dribbling (OR = 4.14, CI 1.93–8.87), impaired taste/smelling (OR = 2.23, CI 1.20–4.13), constipation (OR = 3.42, CI 1.88–6.24), incomplete bowel emptying (OR = 2.23, CI 1.19–4.20), urinary urgency (OR = 2.58 CI 1.46–4.57), nocturia (OR = 2.65, CI 1.49–4.71), hallucinations (OR = 5.32, CI 1.78–15.97), dizziness (OR = 3.03, CI 1.59–5.79), falling (OR = 3.60, CI 1.67–7.77), insomnia (OR = 2.29, CI 1.28–4.11), intense vivid dreaming (OR = 2.10, CI 1.21–3.66) and acting out during dreams (OR = 2.23, CI 1.24–4.01).

Conclusions

PD patients with different ages at onset present clinically different symptoms in terms of NMS. Old-age onset PD is characterized by more olfactory and sensory symptoms, autonomic symptoms, sleep disorders, dementia and psychosis compared to EOPD.     

Bipolar disorder and polymorphisms of glutathione S-transferases M1 (GSTM1) and T1 (GSTT1)

Glutathione S-transferases are ubiquitous multifunctional enzymes, which play a key role in cellular detoxification. The present case-control study was performed in Shiraz, Iran to investigate the association between polymorphisms of glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) and susceptibility to bipolar disorder (BPD). A total of 228 BPD patients participated in the study. In addition, 236 healthy blood donors, who frequency matched with the patients according to age and gender, were also studied as a control group. Statistical analysis revealed that polymorphisms of neither GSTM1 (OR = 0.73, 95% CI: 0.50-1.05) nor GSTT1 (OR = 0.98, 95% CI: 0.65-1.47) were associated with risk of BPD. Patients were stratified according to their age of onset into early onset (below 19 years old) and late onset (more than 19 years old) groups. Among the early onset group, the GSTM1 null genotype decreases the risk of BPD (OR = 0.43, 95% CI: 0.24-0.79). Further analysis showed that a combination of “GSTM1 positive genotype and GSTT1 null genotype” versus “positive genotypes of GSTM1 and GSTT1” increased the risk of BPD (OR = 2.28, 95% CI: 1.07-4.85). However, there was no significant association between the study polymorphisms and risk of BPD among the late onset group. The present finding indicated that GSTM1 and GSTT1 are candidate polymorphisms for susceptibility to BDP among adolescents.     

The association of the JAK2 46/1 haplotype with non-splanchnic venous thrombosis

Background

The inherited JAK2 46/1 haplotype is strongly associated with the development of myeloproliferative neoplasms (MPNs), and its increased frequency has also been reported in splanchnic venous thrombosis (SVT). In the present study, the role of the JAK2 46/1 haplotype in non-splanchnic venous thrombosis (non-SVT) was investigated.

Methods and Results

We genotyped 438 patients with non-SVT, 226 patients with MPNs and 459 healthy controls for three single nucleotide polymorphisms (SNPs) which tag the JAK2 46/1 haplotype (rs12342421 G > C, rs12343867 T > C and rs10974944 C > G). We found statistically significant association of the rs12342421 GC + CC genotypes (OR = 1.40; p = 0.023) and the rs12343867 TC + CC genotypes (OR = 1.83; p = 7.02x10^- 5) with non-SVT. We also found that the CC haplotype of these two SNPs was associated with an increased risk of the disease (OR = 1.68; p = 0.009). Stratification analysis indicated that the observed association of the JAK2 46/1 haplotype with non-SVT was probably largely free of confounding effect of thrombophilic risk factors. In addition, we established a strong association of SNPs rs12342421 and rs10974944 and their CG haplotype with MPNs and with JAK2 V617F-positive MPNs.

Conclusions

This study provides statistical evidence that SNPs rs12342421 and rs12343867 are associated with an increased risk of non-SVT. Consistently, haplotypes of the SNPs were also associated with non-SVT risk, suggesting that inherited genetic variation in the JAK2 gene may play a role in the pathogenesis of non-SVT. Furthermore, the reported associations of the JAK2 46/1 haplotype with MPNs as well as with the occurrence of the JAK2 V617F mutation in MPNs were confirmed.     

Gender differences in the effects of peroxisome proliferator-activated receptor γ2 gene polymorphisms on metabolic adversity in patients with schizophrenia or schizoaffective disorder

Objective

Metabolic syndrome (MS) is a major health problem in schizophrenic patients. Peroxisome proliferator-activated receptor γ2 (PPARγ2) is one of the candidate genes responsible for the liability to metabolic problems. In this study, we investigated the effect of the PPARγ2 gene Pro12Ala and C161T polymorphisms on metabolic adversities in patients with schizophrenia or schizoaffective disorder.

Methods

Metabolic profiles and PPARγ2 gene polymorphisms were determined in 600 patients (309 men and 291 women) with a clinical diagnosis of schizophrenia or schizoaffective disorder. Metabolic indices and components of MS were compared between patients with different Pro12Ala or C161T genotypes.

Results

In the whole population, the allele frequency of 12Ala and 161T was 4.4% and 24.7% respectively. Both polymorphisms had no significant effect on obesity or metabolic-related traits. However, following gender stratification of the data, we found female 12Ala allele carriers were at greater risk of developing abdominal obesity (OR = 4.0, 95% CI = 1.1-14.2, p = 0.04) and hypertension (OR = 2.9, 95% CI = 1.2-7.4, p = 0.02) than female 12Ala allele non-carriers. Male 161T allele carriers had lower insulin levels (p = 0.02) and lower high-density lipoprotein cholesterol (HDL-C) (p = 0.05) levels than male 161T allele non-carriers. Moreover, female 161T allele carriers had higher body weight (p = 0.04), waist circumference (p = 0.05), and systolic blood pressure (p = 0.01), and were at greater risk of developing hypertension (OR = 2.0, 95% CI = 1.1-3.5, p = 0.02). Haplotype analyses showed that PPARγ2 gene polymorphisms were significantly associated with HDL-C level in men and blood pressure in women.

Conclusions

We did not find an association of PPARγ2 gene polymorphisms with MS or obesity in our schizophrenia sample. But further analyses by gender stratification revealed gender-specific differences in the effect of different PPARγ2 genotypes on certain metabolic adversities in these patients.     

Association study of RELN polymorphisms with schizophrenia in Han Chinese population

Schizophrenia (SZ) is a common and complex psychiatric disorder with a strong genetic component. Previous research suggests that mutations altering genes in neurodevelopmental pathways contribute to SZ. Reelin gene (RELN) maps to chromosome 7q22.1, the encoded protein plays a pivotal role in guiding neuronal migration, lamination and connection during embryonic brain development. Several reports had indicated that reduced RELN expression is associated with human mental illnesses such as SZ, mood disorders and autism. In this study, case-control association analyses were performed in the Han Chinese population to determine if the RELN gene is a susceptibility gene for SZ. Thirty-seven single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was found between rs12705169 and SZ (p = 0.001). Moreover, the haplotypes constructed from five SNPs showed significant differences between cases and controls (p = 0.041). When subjects were divided by gender, rs12705169 remained significant difference only in females (OR = 0.24, 95%CI = 0.14-0.40 for CC and OR = 0.40, 95%CI = 0.27-0.58 for AC), both in the allele and genotype (p = 0.0001 for both). This study describes a positive association between RELN and SZ in the Han Chinese population, and provides genetic evidence to support the gender difference of SZ.     

Interleukin 6–174 G/C promoter and variable number of tandem repeats (VNTR) gene polymorphisms in sporadic Alzheimer's disease

Background

Previous studies examining the association between the interleukin 6 (IL-6)–174 C/G polymorphism and Alzheimer's disease (AD) have yielded conflicting results. Furthermore, the C allele of the IL-6 variable number of tandem repeats (VNTR) polymorphism was associated with a delayed onset and a decreased risk of AD.

Methods

A total sample of 149 AD patients, and 298 age- and sex-matched unrelated caregivers from Apulia, southern Italy, were genotyped for the apolipoprotein E (APOE) polymorphism, the VNTR polymorphism in the 3' flanking region, and the -174G/C single-nucleotide polymorphism (SNP) in the promoter region of IL-6 gene on chromosome 7. Furthermore, we performed a haplotype analysis on these two polymorphisms on IL-6 locus.

Results

IL-6 VNTR and -174G/C allele and genotype frequencies were similar between AD patients and controls, also after stratification for late-onset (≥ 65 years) and early-onset (< 65 years) or APOE ε4 status. Furthermore, there was no evidence of linkage disequilibrium between the VNTR and -174G/C polymorphisms, not supporting a previous reported additive effect of both IL-6 polymorphisms on AD risk.

Conclusions

Our findings did not support a role of IL-6–174 G/C and IL-6 VNTR polymorphisms in the risk of sporadic AD in southern Italy, suggesting that these polymorphisms of IL-6 gene were at most weak genetic determinants of AD.