Impact of insurance status and race on receipt of treatment for acoustic neuroma: A national cancer database analysis

Acoustic neuroma (AN) management involves surgery, radiation, or observation. Previous studies have demonstrated that patient race and insurance status impact in-hospital morbidity/mortality following surgery; however the nationwide impact of these demographics on the receipt of each treatment modality has not been examined. The National Cancer Data Base (NCDB) from 2004 to 2013 identified AN patients. Multivariate analysis adjusted for several variables within each treatment modality, including patient age, race, sex, income, primary payer for care, tumor size, and medical comorbidities. Patients who were African-American (OR = 0.7; 95%CI = 0.5–0.9; p = 0.01), elderly (minimum age 65) (OR = 0.4; 95%CI = 0.4–0.6; p < 0.0001), on Medicare (OR = 0.6; 95% CI = 0.4–0.7; p = 0.0005), or treated at a community hospital (OR = 0.4; 95%CI = 0.2–0.7; p = 0.007) were less likely to receive surgery. Patients on Medicaid (OR = 1.2; 95%CI = 0.8–1.8; p = 0.04) or treated at an integrated network (OR = 1.2; 95%CI = 0.9–1.6; p = 0.0004) were more likely to receive surgery. Patients who were elderly (OR = 2.2; 95%CI = 1.7–2.9; p < 0.0001) or treated in a comprehensive cancer center (OR = 1.5; 95%CI = 1.3–1.9; p = 0.02) were more likely and Medicaid patients (OR = 0.8; 95%CI = 0.5–1.2; p = 0.04) were less likely to receive radiation. Patients who were elderly (OR = 2.2; 95%CI = 1.7–2.7; p < 0.0001), African-American (OR = 1.5; 95%CI = 1.1–2.0; p = 0.01), on Medicare (OR = 1.8; 95%CI = 1.4–2.3; p = 0.0003), or treated in a community hospital (OR = 3.0; 95%CI = 1.6–5.6; p = 0.0007) were more likely to receive observation. Patients on Medicaid (OR = 0.8; 95%CI = 0.5–1.2; p = 0.04) or treated in an integrated network (OR = 0.8; 95%CI = 0.6–1.0; p = 0.0001) were less likely to receive observation. African-American race, elderly age, and community hospital treatment triaged towards observation/away from surgery; age also triaged towards radiation. Conversely, integrated networks triaged towards surgery/away from observation; comprehensive cancer centers triaged towards radiation. Medicaid insurance triaged towards surgery/away from radiation/observation; this may be detrimental since lack of private insurance is a known risk factor for increased in-hospital postoperative morbidity.     

rs2070424 of the SOD1 gene is associated with risk of Alzheimer's disease

ObjectiveOxidative stress plays an important role in Alzheimer's disease (AD) etiopathogenesis. There were several studies that showed impaired antioxidant defense system (ADS) enzymes expression or activity in AD patients. There are only few studies evaluating the importance of ADS gene single nucleotide polymorphisms (SNPs) as risk factors of AD. We evaluated association between chosen SNPs of the enzymes of the ADS and risk of AD.MethodsWe included 400 AD patients and 402 healthy controls. We studied rs1041740, rs4998557 and rs2070424 of the SOD1 gene, rs2855116, rs5746136 and rs4880 of the SOD2 gene and rs3448, rs1050450 and rs1800668 of the GPx-1 gene (real time PCR). To determine the APOE gene common polymorphism, two single-nucleotide polymorphisms (SNPs; NCBI SNPs rs429358 and rs7412) were genotyped (TaqMan assays, Applied Biosystems [ABI], Foster City, CA, USA). The genotype and gender frequencies were compared between the studied groups by the χ² test and mean age by the t-Student test.ResultsAmong all studied SNPs only rs2070424 of the SOD1 gene was a protective factor for AD in an additive (OR = 0.47; 95% CI = 0.30–0.74, p = 0.001) and recessive (OR = 0.47; 95% CI = 0.30–0.75, p = 0.002) models including age, gender and APOE gene status.Conclusionsrs2070424 polymorphism of the SOD1 gene is a risk factor for AD in Polish population. Allel G and genotype AG and GG are protective factors for AD.     

Variant rs1906591 on chromosome 4q25 confers increased risk of cardioembolic stroke in Chinese patients

Ischemic stroke (IS) is a heterogeneous multifactorial disorder caused by both genetic and environmental factors. A genome-wide association study on stroke in Caucasians identified a variant on chromosome 4q25 that is significantly associated with IS, with the strongest risk for cardioembolic stroke (CES). The current study aims to investigate the association of the rs1906591 variant on 4q25 with IS through a case-control study in a Chinese Han population. A total of 712 IS patients and 774 control subjects were involved in the current research. Stroke subtyping was performed according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The genotypes were determined using the SNaPshot technique. The association of the genotypes with the risk of IS was estimated using logistic regression analysis. The rs1906591 single nucleotide polymorphism variant was associated with the CES subtype in both recessive and additive models (recessive model: odds ratio [OR] = 2.58, 95% confidence interval [CI] 1.47–4.53, p = 0.001, adjusted OR = 2.71, 95% CI 1.48–4.96, p = 0.001; additive model: OR = 2.50, 95% CI 1.19–5.25, p = 0.015, adjusted OR = 2.83, 95% CI 1.24–6.50, p = 0.013). This result indicates that patients with the AA genotype have a higher rate of CES than other genotypes. However, the rs1906591 variant was not significantly associated with the overall incidence of stroke or other stroke subtypes. The rs1906591 variant is significantly associated with CES in the Chinese Han population, but not with other stroke subtypes.     

Rs3761389 polymorphism in autoimmune regulator (AIRE) gene is associated with susceptibility of myasthenia gravis in Chinese patients

Polymorphism in autoimmune regulator (AIRE) gene is associated with various autoimmune disorders. Abnormal AIRE expression is associated with the development of myasthenia gravis (MG). We investigated the association of polymorphism in AIRE gene and the clinical features and severity of MG. The frequencies of alleles and genotypes were compared between 480 MG patients and 487 healthy controls, as well as among subgroups of MG patients. The frequencies of rs3761389 G allele in MG group (OR = 1.213, CI 95% 1.014–1.451, p = 0.035) and in mild (Oosterhuis score 0–2) subgroup (OR = 1.393, CI 95% 1.110–1.751, p = 0.004) were significantly higher than those in the control group. There were significant differences in the frequencies of rs3761389 genotypes (OR = 1.20, CI 95% 1.00–1.43, p = 0.046, log-additive model) and mild subgroup (OR = 1.32, CI 95% 1.03–1.69, p = 0.0058, log-additive model) compared with the control group. A Logistic regression analysis did not identify rs3761389 genotype as an independent risk factor to predict the severity of MG. This study provides the necessary preliminary data on the association with rs3761389 in AIRE gene with the susceptibility of MG, but not with the severity of MG.     

Neuropeptide Y associated with asthma in young adults

ObjectiveNeuropeptide Y, a widely circulating neurotransmitter, plays a pivotal role in energy balance, immunomodulation and asthma, and several NPY polymorphisms are promising genetic risk factors for asthma and obesity. We explored the associations of candidate NPY gene polymorphisms with prevalent asthma and its relationship with obesity in young adult asthma patients free of other chronic medical morbidity.MethodsFive common gene variants of NPY (rs16147 (− 399T/C), rs17149106 (− 602G/T), rs16140 (+ 1000C/G), rs5573 (+ 1201A/G), rs5574 (+ 5327C/T)) previously validated to account for most of the NPY expression in vitro and in vivo were investigated in 126 physician-diagnosed asthma patients without other chronic medical morbidity and 182 healthy controls (21–35 years). Plasma levels of NPY, adiponectin, and CRP were determined using ELISA, and IL-6 was measured by Luminex in a subgroup of 70 patients and 69 age- and sex-matched healthy controls.ResultsIn logistic regression models controlling for gender and obesity, the CT genotype of rs5574 (OR = 0.54, 95%CI: 0.30–0.89) and the GT genotype of rs17149106 (OR = 5.58, 95%CI: 1.09–28.54) were significantly associated with asthma. No significant interaction between NPY SNP polymorphisms and obesity were detected. Plasma NPY level was correlated with adiponectin levels (p < 0.05). Compared with the healthy controls, patients with asthma had higher BMI (p < 0.001), adiponectin (p < 0.05), IL-6 (p = 0.001) and CRP (p < 0.001), and lower NPY levels (p < 0.01).ConclusionsThe CT genotype of rs5574 and the GT genotype of rs17149106 are significantly associated with prevalent asthma.     

Tryptophan hydroxylase 2 (TPH2) gene polymorphisms and psychiatric comorbidities in temporal lobe epilepsy

Psychiatric comorbidities are frequent in temporal lobe epilepsy (TLE). It is plausible that variance in serotonin-related genes is involved in the susceptibility of these associations. We report here the results on the association of tryptophan hydroxylase 2 (TPH2) gene polymorphisms with psychiatric comorbidities in TLE. A cohort study was conducted on 163 patients with TLE. We assessed the influence of the rs4570625 and rs17110747 polymorphisms in the TPH2 gene on psychiatric comorbidities in TLE. In patients with TLE, the presence of the T allele in the rs4570625 polymorphism was associated with psychotic disorders (OR = 6.28; 95% CI = 1.27–17.54; p = 0.02), while the presence of the A allele in the rs17110747 polymorphism was associated with alcohol abuse (OR = 20.33; 95% CI = 1.60–258.46; p = 0.02). Moreover, we identified male gender (OR = 11.24; 95% CI = 1.68–76.92; p = 0.01) and family history of psychiatric disorder (OR = 15.87; 95% CI = 2.46–100; p = 0.004) as factors also associated with alcohol abuse in TLE. Conversely, a family history of epilepsy was inversely associated with alcohol abuse (OR = 0.03; 95% CI = 0.001–0.60; p = 0.02). Tryptophan hydroxylase 2 gene allele variants might be risk factors for psychiatric conditions in TLE. More specifically, we observed that the T allele in the rs4570625 polymorphism was associated with psychotic disorders, and the A allele in the rs17110747 TPH2 polymorphism was associated with alcohol abuse in patients with TLE. We believe that this study may open new research venues on the influence of the serotonergic system associated with psychiatric comorbidities in epilepsy.     

Genetic variants on chromosome 9p21 and ischemic stroke in Chinese

In a hospital based case control study, we investigated the association of cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, cyclin-dependent kinase inhibitor 2B (CDKN2B) gene, and two genetic variants (rs10757274 and rs2383206) on chromosome region 9p21 with ischemic stroke in Chinese Hans. Two polymorphisms in the CDKN2A gene (rs3088440 and rs3731245) and two polymorphisms in the CDKN2B gene (rs3217992 and rs1063192) were selected by using a strategy of tagging single nucleotide polymorphisms (tSNP). We observed significant association of rs2383206 with ischemic stroke. Subjects with the GG/GA genotype of rs2383206 had a 1.51-fold (95%CI 1.11–2.05, p = 0.009) increased risk of stroke, compared with those with the AA genotype. In addition, the GG/GA genotypes of rs2383206 and rs3731245 was associated with an increased risk of large vessel subtype and small vessel subtype of ischemic stroke, respectively, with ORs of 2.09 (95%CI 1.30–3.37, p = 0.002) and 1.63 (95%CI 1.06–2.51, p = 0.026), respectively. In gene–environmental interaction analysis, elevation of ischemic stroke risk was observed among AG + GG genotype carriers who consume alcohol, smoke cigarette, and have hypertension, with adjusted combined ORs of 2.86(1.51–5.41), 4.30(2.38–7.77), and 13.97(7.78–25.07), respectively, compared with low-risk individuals for rs2383206 (GG carriers who did not consume alcohol, smoke cigarette, and without hypertension). We provide evidence that genetic variants on chromosome region 9p21 may implicated in the prevalence of ischemic stroke in Chinese.     

Complications and operative spine fusion construct length in Parkinson’s disease: A nationwide population-based analysis

There remains a dearth of information regarding the surgical complications following multilevel spine surgery in Parkinson’s disease (PD) patients. This retrospective cohort study was performed to address this issue on a nationwide level using the Nationwide Inpatient Sample from 2001 to 2012. More than 25 postoperative variables were analyzed to assess the impact of fusion construct length on each variable. Subsequently, the same analysis was performed on admissions without PD. 4301 PD patients with spine fusion were identified, of whom 934 (21.7%) underwent fusion of at least three levels; the remaining 3367 underwent fusion of 1–2 levels. Patients with 3+ level fusions were more likely to suffer paraplegia (P = .001; OR = 3.0; 95%CI = 1.5–6.1), hematoma/seroma (P = .009; OR = 1.9; 95%CI = 1.2–3.2), IVC filter placement (P = .018; OR = 2.1; 95%CI = 1.1–3.9), RBC transfusion (P < .001; OR = 3.2; 95%CI = 2.7–3.8), PE (P = .027; OR = 4.5; 95%CI = 1.2–16.9), postoperative shock (P = .023; OR = 7.3; 95%CI = 1.3–39.6), ARDS (P < .001; OR = 4.1; 95%CI = 2.7–6.3), VTE (P = .006; OR = 2.6; 95%CI = 1.3–5.4), acute posthemorrhagic anemia (P < .001; OR = 2.0; 95%CI = 1.7–2.4), device-related complications (P < .001; OR = 3.1; 95%CI = 2.3–4.2), and in-hospital mortality (P = .005; OR = 3.4; 95%CI = 1.5–7.4). 3+ level fusions were also more likely to have LOS > 1 week (P < .001; OR = 2.1; 95%CI = 1.8–2.5), and a nonroutine discharge (P = .005; OR = 1.9; 95%CI = 1.4–2.4). 692,173 non-PD patients with spine fusion were identified; 123,964 (17.9%) underwent 3+ level fusion. Differences between 3+ versus 1–2 level fusions were similar to those in PD patient, but unlike PD patients, postoperative infection was significant while in-hospital mortality, PE and VTE were not. Fusion of at least three levels increased morbidity, mortality, and adverse discharge disposition compared with 1–2 level fusions. Nearly 80% of all spine fusions performed in the United States are fewer than three levels. These findings are worth considering during operative decision-making in both PD and non-PD patients.     

Serotonin genes and gene–gene interactions in borderline personality disorder in a matched case-control study

Lines of evidence suggest serotonin genes are susceptibility candidates in borderline personality disorder (BPD). However, few molecular genetic studies on BPD have been reported, especially an overall lack of study on epistatic interactions. We genotyped 27 polymorphisms in 7 serotonin genes in 113 Caucasian BPD patients and matched (sex, age and ethnicity) controls. Program UNPHASED was used to perform association analyses for genotypes, alleles and haplotypes with a permutation test of 10,000 simulations. The Multifactor Dimensionality Reduction analysis was used to examine gene–gene interactions in serotonin system, including three other genes (5-HTT, 5-HT2A and MAOA) that we previously reported. Genotype and allele analyses showed that BPD significantly associated with 5-HT2C and TPH2. BPD patients had high frequencies of the 5-HT2C rs6318G allele (p = 0.021) and G/G genotype (OR = 2.25); and TPH2 rs2171363T allele (p = 0.001) and T containing genotypes (OR = 3.40). The 5-HT1A, 5-HT1B, 5-HT1D, 5-HT3A and TPH1 showed no significant association with BPD for genotype, allele and haplotype analyses. We also detected significant interactions between 5-HT2C and TPH2 (p = 0.001), and among 5-HT2C, 5-HTT, MAOA and TPH2 (p = 0.001) in BPD. Patients with 5-HT2C rs6318G/G genotype had a high frequency of TPH2 rs2171363C/T genotype compared with controls. Our study indicates ““that serotonin genes and their interactions may play a role in the susceptibility to borderline personality disorder.     

Comorbidity of allergic and autoimmune diseases in patients with autism spectrum disorder: A nationwide population-based study

Previous clinical and genetic studies have suggested autism spectrum disorders (ASDs) is associated with immunological abnormalities involving cytokines, immunoglobulins, inflammation, and cellular immunity, but epidemiological reports are still limited. Patients with ASDs were identified in the National Health Insurance Database from 1996 to 2010, and compared with age and gender-matched controls (1:4) in an investigation of the association between ASDs and allergic/autoimmune diseases. A total of 1596 patients with ASDs were identified, and were found to have a significantly higher prevalence of allergic and autoimmune diseases than the control group. Patients with ASDs had increased risks of asthma (OR = 1.74, 95%CI = 1.51–1.99), allergic rhinitis (OR = 1.70, 95%CI = 1.51–1.91), atopic dermatitis (OR = 1.52, 95%CI = 1.30–1.78), urticaria (OR = 1.38, 95%CI = 1.12–1.69) and type 1 diabetes (OR = 4.00, 95%CI = 1.00–16.00), and a trend toward increasing comorbidity with Crohn's disease (OR = 1.46, 95%CI = 0.90–2.35). Our results support the association between ASDs and allergic diseases, and autoimmune comorbidities (type 1 diabetes and Crohn's disease). Further basic study is required to elucidate the possible underlying mechanisms and roles of allergy immunity and autoimmunity in the etiology of ASDs.     

Three polymorphisms of ALOX5AP and risk of ischemic stroke in Chinese: Evidence from a meta-analysis

The impacts of three polymorphisms (SG13S114A/T, SG13S89A/G and SG13S32A/C) of 5-lipoxygenase activating protein (ALOX5AP) on the risk of ischemic stroke (IS) have been extensively studied for Chinese people, while conflicting results have been reported. The aim of meta-analysis was to further explore the associations to get a more robust conclusion. We researched the databases of Medline, Embase and Wangfang with latest update of August 1st, 2013. Odds ratio and corresponding 95% confidence interval (OR and 95%CI) were used to present the strength of the associations. Eleven case–control studies with 11,037 Chinese peoples (5361 IS cases and 5676 controls) were included. Overall, combined analysis indicated that AA genotype of ALOX5AP SG13S114A/T was significantly associated with increased risk of IS incidence compared with TT genotype [OR and 95%CI: 1.47 (1.13–1.91), P = 0.005]. In addition, when subgroup analysis was conducted by subtypes of IS (atherothrombotic- or small artery disease-IS, AHS- or SAD-IS), A allele of SG13S114A/T was found to be associated with increased risk of AHS-IS compared with T allele [OR and 95%CI: 1.51 (1.28–1.79), P < 0.01 for AA vs. TT, and 1.12 (1.03–1.22), P = 0.010 for A carriers v. T carriers]. However, SG13S89A/G and SG13S32A/C were not overall associated with IS incidence. Due to limited number of included studies, subgroup analyses were not conducted for SG13S89A/G and SG13S32A/C polymorphisms. Sensitivity analyses indicated the robustness of all combined analyses, and publication bias was not found. In conclusion, ALOX5AP SG13S114A/T, rather SG13S89A/G and SG13S32A/C, was significantly associated with risk of IS development for Chinese. More studies were required to warrant the findings of this study.     

Association of alpha subunit of GABAA receptor subtype gene polymorphisms with epilepsy susceptibility and drug resistance in north Indian population

GABA (γ-amino butyric acid) receptors have always been an inviting target in the etiology and treatment of epilepsy because of its role as a major inhibitory neurotransmitter in the brain. The aim of our study was to find out the possible role of single nucleotide polymorphisms (SNPs) present in GABRA1 IVS11 + 15 A > G (rs2279020) and GABRG2 588C > T (rs211037) genes in seizure susceptibility and pharmaco-resistance in northern Indian patients with epilepsy. A total of 395 epilepsy patients and 199 control subjects were enrolled for present study. The genotyping was done by PCR-RFLP methods. The GABRA1 IVS11 + 15 A > G polymorphism conferred high risk for epilepsy susceptibility at genotype ‘AG’ (P = 0.004, OR = 1.77, 95% CI = 1.20–2.63), ‘GG’ (P = 0.01, OR = 1.80, 95% CI = 1.15–2.80) and G allele level (P = 0.001, OR = 1.50, 95% CI = 1.16–1.92). Moreover this polymorphism was also associated with multiple drug resistance in patients with epilepsy for homozygous variant ‘GG’ genotype (P = 0.031, OR = 1.84, 95% CI = 1.05–3.23) and G allele (P = 0.020, OR = 1.43, 95% CI = 1.05–1.95). However GABRG2 588C > T polymorphism was not found to be associated either with epilepsy susceptibility or with drug resistance. Overall results indicate differential role of different subunits of GABA_A receptor subtypes in epilepsy susceptibility and pharmacotherapy.     

Association analysis of TPH-1 and TPH-2 genes with suicidal behavior in patients with attempted suicide in Mexican population

BackgroundSuicidal behavior is a worldwide health problem. Tryptophan hydroxylase (TPH) is a rate limiting enzyme in the biosynthesis of serotonergic neurotransmission. TPH-1 and TPH-2 genes encode for TPH isoforms and have been implicated as candidate genes for suicidal behavior. The aim of this study was to evaluate the association between the genetic variants of the TPH-1 (rs21102 and 1607395) and TPH-2 (rs4290270, rs7305115 and rs1007023) genes and suicidal behavior in a Mexican population.MethodsWe conducted a case-control study including 200 cases with suicide attempt and 263 controls. Patients were evaluated by a trained psychiatrist or clinical psychologists. Five polymorphisms were genotyped and assessed for allele, genotype and haplotype association with suicide attempt.ResultsThe rs7305115 polymorphism of the TPH-2 gene was associated with suicidal behavior in a Mexican population in genotype (χ² = 6.02, df = 2, p = 0.04) and allele (OR = 1.39, 95%IC = 1.06–1.81, p = 0.01) frequencies. The THP-2 haplotypes GTA (χ² = 5.68, p = 0.01) and ATT (χ² = 5.0, p = 0.02) were associated with risk for suicide attempt.ConclusionOur results provide evidence for an association between the rs7305115 polymorphism of the TPH-2 gene and suicidal behavior in a Mexican population. However, more studies are necessary to replicate these results using larger samples.     

The role of fibroblast growth factor receptor 4 polymorphisms in the susceptibility and clinical features of ischemic stroke

Some polymorphisms in the fibroblast growth factor receptor 4 gene (FGFR-4) have been correlated with coronary artery disease, however, the role of polymorphisms in the FGFR-4 gene in ischemic stroke remain unknown. A total of 270 patients with ischemic stroke and 297 controls were recruited. Stroke subtype was classified and clinical severity of stroke in patients was evaluated. The polymorphisms in the FGFR-4 were genotyped. There were no significant differences of genotype distributions and allele frequencies of rs145302848C/G and rs147603016G/A between stroke patients and controls (all p > 0.05). However, genotype frequencies and allele frequencies at rs351855G/A (Gly388Arg) were significantly different between stroke patients and controls (both p < 0.001). With the rs351855GG genotype as a reference, the presence of rs351855AA homozygote had a significantly increased risk for stroke (adjusted odds ratio 2.663; 95% confidence interval 1.673–4.229, p < 0.001). The polymorphisms at rs145302848C/G and rs147603016G/A did not influence the susceptibility of stroke in this study. All FGFR-4 polymorphisms were not associated with clinical features such as Trial of Org 10172 in Acute Stroke Treatment subtype or stroke severity as indicated by mean National Institutes of Health Stroke Scale scores. Our study suggests a positive association between FGFR-4 gene polymorphism at rs351855G/A and susceptibility to ischemic stroke.     

Further evidence for genetic association of CACNA1C and schizophrenia: New risk loci in a Han Chinese population and a meta-analysis

CACNA1C (12p13.3) has been implicated as a susceptibility gene for schizophrenia by several replicated genome wide association studies. While these results have been consistent among studies in European populations, the findings in East Asian populations have varied. To test whether CACNA1C is a risk gene for schizophrenia, we conducted a case–control study in 5897 schizophrenic patients and 6323 healthy control subjects selected from Han Chinese population. Our study replicated the positive associations of rs1006737 (P = 0.0108, OR = 1.16, 95% CI: 1.03–1.29) and rs1024582 (P = 0.0062, OR = 1.18, 95% CI: 1.05–1.33), and identified a novel risk locus, rs2007044 (P = 0.0053, OR = 1.08, 95% CI: 1.02–1.14). A meta-analysis of rs1006737 combining our study and previous studies was conducted in a total of 8222 schizophrenia cases and 24,661 healthy controls. In the meta-analysis, the association between rs1006737 and schizophrenia remained significant (OR = 1.14, 95% CI: 1.07–1.22, P = 0.0001). Stratified analysis showed no heterogeneity between East Asian and European ancestries (χ²[1] = 0.07, P = 0.795), and the difference in pooled ORs between ancestries was not significant (Z = 0.25, P = 0.801). Our results provide further support for associations of rs1006737 and rs1024582 with schizophrenia, identify a new risk locus rs2007044 in a Han Chinese population, and further establish CACNA1C as an important susceptibility gene for the disease across world populations.     

The rs522616 polymorphism in the matrix metalloproteinase-3 (MMP-3) gene is associated with sporadic brain arteriovenous malformation in a Chinese population

In this study, we investigated the association between common variants in the matrix metalloproteinase-3 (MMP-3) gene and the risk of developing sporadic brain arteriovenous malformation (BAVM). We performed genotyping analyses for five single nucleotide polymorphisms (SNPs) in MMP-3 in a case-control study involving 319 Chinese patients with BAVM and 333 Chinese controls. The association between MMP-3 genotypes and the risk of developing BAVM was evaluated using logistic regression analyses. We found that the genotype frequencies were significantly different between patients and controls for the rs522616 A > G variant of MMP-3 (p = 0.02). Logistic regression analysis revealed that the variant genotype of this polymorphism was associated with a significantly decreased risk of BAVM (adjusted odds ratio = 0.62, 95% confidence interval = 0.44–0.87, p = 0.006 for the AG compared with the AA genotype; adjusted odds ratio = 0.68, 95% confidence interval = 0.49–0.94, p = 0.019 for the AG + GG compared with the AA genotype). These findings indicate for the first time that the MMP-3 rs522616 polymorphism may contribute to the etiology of sporadic BAVM in the Chinese population.     

Association of polymorphisms in the LRP1 and A2M genes with Alzheimer’s disease in the Northern Chinese Han population

Low-density lipoprotein receptor-related protein1 (LRP1) and alpha-2-macroglobulin (A2M) are candidate genes for sporadic Alzheimer’s disease (SAD). It is not clear whether the LRP1 exon 3 and A2M exon 24 polymorphisms are associated with SAD. In the present study, we used direct sequencing to genotype the LRP1 C766T (rs1799986) polymorphism in exon 3 and the A2M I1000V (rs669) polymorphism in exon 24 in 364 patients with SAD and 291 healthy control subjects from the Northern Chinese Han population. The distributions of LRP1 genotypes (chi-squared [χ²] = 7.25, degrees of freedom [d.f.] = 2, p = 0.027) and alleles (χ² = 8.154, d.f. = 1, p = 0.004) were significantly different between patients and controls who were apolipoprotein E (APOE) ε4 positive. The T allele and TT+TC genotype were associated with a reduced risk of developing SAD (T allele: odds ratio [OR] = 0.541, 95% confidence interval [CI] = 0.368–0.859, p = 0.005; TT+TC genotype: OR = 0.613, 95% CI = 0.315–0.725, p = 0.012). There was no statistically significant difference in allele and genotype frequencies between patients with SAD and control subjects for the A2M I1000V polymorphism, even after stratification by age of onset, gender, and APOE ε4 status. We found an interaction between LRP1 and APOE genotypes (p = 0.001), but no interaction between LRP1 and A2M genotypes. Our results suggest that the T allele of the LRP1 C766T polymorphism is associated with a decreased risk of SAD in APOE ε4 carriers from the Northern Han Chinese population.     

Effects of glutathione S-transferase M1 and T1 deletions on Parkinson's disease risk among a North African population

PurposeIn this study, the effects of glutathione S-transferase polymorphisms Mu1 (GSTM1) and glutathione S-transferase polymorphisms Theta1 (GSTT1) on Parkinson's disease (PD) risk factor were evaluated in a Tunisian population.MethodsThese polymorphisms were analyzed in 229 healthy Tunisian subjects and 64 Tunisian patients with PD, using a polymerase chain reaction (PCR). Statistical analysis was performed using SPSS 18.0. The relative associations between the GST genotypes and PD were assessed by calculating the odds ratios (ORs) and 95% confidence intervals (CIs).ResultsThe study results demonstrated that the individuals with GSTM1 [OR = 3.93, 95% CI: 1.98–7.92, P = 10^?6] and GSTT1 [OR = 5.45, 95% CI: 2.90–10.30, p = 10^?6] were statistically associated with the risk of PD. A significant association was also found between the individuals with both GSTM1/T1 null genotypes and PD risk [OR = 22.10, 95% CI: 6.99–73.75, P = 10^?6].ConclusionThese genotyping findings suggest that the absence of both GSTM1 and GSTT1 activity could be a contributory factor for the development of PD.     

CYP2D6 phenotypes and Parkinson's disease risk: A meta-analysis

BackgroundCYP2D6 polymorphisms have been reported to be associated with Parkinson's disease (PD) susceptibility, but the results of these previous studies were inconsistent.ObjectivesTo explore whether PD patients with CYP2D6 gene variation have different risk to PD to those with normal function of CYP2D6.MethodsSystematic review with meta-analysis of case-controlled studies on the association between CYP2D6 and PD risk was conducted. Studies published up to August 1, 2013 were identified by searching electronic databases PubMed and Embase. Odds ratios (ORs) together with their corresponding 95% confidence intervals (CIs) were used to estimated the association between CYP2D6 polymorphisms and PD risk in different phenotype models. Meta-regression, subgroup analysis, sensitivity analysis and publication bias were also performed.ResultsA total of 3521 PD Patients and 4476 controls from 29 case–control studies were identified. Overall, a borderline significant influence of the CYP2D6 polymorphisms on PD risk was observed (OR: 1.07, 95%CI: 0.99–1.16, p = 0.106). Significant association was found when comparisons were performed in different phenotypes in PM versus EM (OR = 1.33, 95% CI = 1.01–1.74, p = 0.044) and PM versus IM + EM (OR = 1.32, 95% CI = 1.11–1.56, p = 0.002). In subgroup analysis stratified by country, significant association was demonstrated in British but not in other white subjects. No significant association was detected in subgroup analysis according to the age of onset and the source of patients.ConclusionThe present meta-analysis demonstrated that the poor metabolizer phenotype of CYP2D6 confers a significant genetic susceptibility to PD in Caucasians, especially in British white subjects.     

The ABCC2 c.-24C > T polymorphism increases the risk of resistance to antiepileptic drugs: A meta-analysis

Several studies examined a possible link between multidrug resistance-associated protein 2 (ABCC2) gene variants and the risk of resistance to antiepileptic drugs (AEDs) in epilepsy, but the results were contradictory. In this study, a meta-analysis was conducted to assess the relevance of ABCC2 common variants (c.-24C > T, c.1249G > A, c.3972C > T) with the response risk of AEDs. We searched Embase, PubMed, the Cochrane Library and CNKI databases for case-control studies published through May 2016 that evaluated the role of ABCC2 gene variants in pharmacoresistance to AEDs. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated to assess the strength of associations between the ABCC2 c.-24C > T, c.1249G > A and c.3972C > T variants and the risk of resistance to AEDs using an allele frequency model, dominant model and recessive model. Subgroup analyses were performed by ethnicity and the definition of drug-resistance. A total of 13 published studies involving 4300 patients (2261 patients with drug-resistant epilepsy and 2039 controls with drug-responsive epilepsy) met the selection criteria. We observed that the variant c.-24C > T was associated with a significantly increased risk of AED resistance (TT + CT vs CC: OR = 1.24, 95%CI = 1.06–1.46, p = 0.009; TT vs CT + CC: OR = 1.90, 95%CI = 1.31–2.76, p = 0.0008; T vs C: OR = 1.27, 95%CI = 1.11–1.46, p = 0.0006). However, we identified no significant association of the ABCC2 c.1249G > A, c.3972C > T variants and haplotypes with the response to anticonvulsant drug in the overall population. In summary, these observations suggest that the ABCC2 c.-24C > T polymorphism is a likely risk factor for resistance to AEDs.