TCF4 gene polymorphism and cognitive performance in patients with first episode psychosis

BackgroundSingle nucleotide polymorphisms in TCF4 gene have been consistently associated with schizophrenia in genome wide association studies, including the C allele of rs9960767. However, its exact role in modulating the schizophrenia phenotype is not known.AimsTo comprehensively investigate the relationship between rs9960767 risk allele (C) of TCF4 and cognitive performance in patients with first episode psychosis (FEP).Methods173 patients with FEP received a comprehensive neurocognitive evaluation and were genotyped for rs9960767. Carriers of the risk allele (CA/CC) were compared to non-carriers (AA) using Multivariate Analysis of Covariance MANCOVA. Ethnicity, negative symptoms and substance abuse were included as covariates.ResultsCarriers of the risk allele had a statistically significant lower performance in the cognitive domain of Reasoning/Problem-Solving compared to non-carriers (F_1,172 = 4.4, p = .038). There were no significant genotype effects on the other cognitive domains or general cognition. This effect on the Reasoning/Problem-Solving domain remained significant even when controlling for IQ (F_1,172 = 4.3, p = .039).Conclusionsrs9960767 (C) of TCF4 appears to be associated with neurocognitive deficits in the Reasoning/Problem-Solving cognitive domain, in patients with FEP. A confirmation of this finding in a larger sample and including other TCF4 polymorphisms will be needed to gain further validity of this result.     

miRNA-146a基因多态性与婴儿痉挛的相关性

目的 探讨我国中部地区汉族人群中miR-146a基因SNP位点(rs2910164和rs57095329)多态性与婴儿痉挛易感性的关系.方法 采用病例对照研究方法,选取在武汉大学人民医院儿科188例婴儿痉挛患者为研究组,选取同期体检的健康儿童214名为对照组.利用PCR-RFLP方法检测rs2910164和rs57095329两个SNP位点的多态性分布.结果 miR-146a基因SNP位点rs57095329基因型(GG、AG、AA)频率分布和G等位基因频率与对照组比较,差异均有统计学意义(P＜0.05),但该位点基因频率与婴儿痉挛发作频率无相关性(P＞0.05).SNP位点rs2910164的基因型(CC、CG、GG)频率和等位基因C与对照组比较,差异均无统计学意义(P＞0.05).结论 位于miR-146a启动子区域的SNP位点rs57095329的多态性与婴儿痉挛的发病相关,但与其发作频率无相关性;而SNP位点(rs2910164)与婴儿痉挛的易感性不相关.     

The SNP rs1625579 in miR-137 gene and risk of schizophrenia in Chinese population: A meta-analysis

BackgroundSchizophrenia is a severe psychiatric disorder with a high heritability. A single nucleotide polymorphism (SNP) rs1625579 (G/T; T is the common and presumed risk allele) within an intron of miR-137 gene has been recently suggested to contribute to the susceptibility to schizophrenia by a large-scale genome-wide association study (GWAS) in a sample of predominantly European ancestry. However, subsequent genetic association studies in Chinese population yielded inconsistent results.MethodsA meta-analysis reporting the association between rs1625579 and schizophrenia in Chinese population was carried out, pooling 4 eligible case–control studies involving 2847 patients and 3018 controls.ResultsThis meta-analysis demonstrated a significant association between rs1625579 and schizophrenia under the allele model [T versus G, odds ratio (OR):1.20, 95% confidence interval (CI): 1.06–1.36] and the recessive model (TT versus GT + GG; OR: 1.19; 95% CI: 1.04–1.37). Additionally, a marginal significant association under the additive model (TT versus GG; OR: 1.64; 95% CI: 1.00–2.69) was observed. However, no significant association was observed under the dominant model (TT + GT versus GG; OR: 1.58; 95% CI: 0.97–2.59).ConclusionsThis meta-analysis suggested that the SNP rs1625579 in miR-137 gene might be involved in schizophrenia susceptibility in Chinese Han population.     

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.     

miR146a基因多态性与早发型阿尔茨海默病的关联性研究

目的 探讨miR146a的基因多态性与早发型阿尔茨海默病（EOAD）的关系.方法 本研究共纳入103例EOAD患者和100名健康对照组人群,采用SnapShot分型技术检测miR146a基因的rs2910164和rs57095329的多态性.结果 病例组的rs57095329位点的基因型和等位基因频率与健康对照组比较,差异有统计学意义（基因型P=0.027 0,等位基因频率P=0.004 2）,而rs2910164的病例组和对照组基因型和基因频率差异无统计学意义（基因型P=0.595 7,等位基因频率P=0.322 6）.结论 miR146a基因的rs57095329多态位点与EOAD的发病风险具有相关性,rs57095329的G等位基因是EOAD的发病风险的保护因素.     

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.     

MIR137 gene and target gene CACNA1C of miR-137 contribute to schizophrenia susceptibility in Han Chinese

Recently, evidence has accumulated indicating that the MIR137 gene and the target gene CACNA1C of miR-137 might be two of the most robustly implicated genes in schizophrenia. In this study, we examined 33 single nucleotide polymorphisms (SNPs) located in two genes by performing an association analysis in a cohort of 1430 schizophrenia patients and 1570 healthy Han Chinese control subjects. Single SNP association, sex-specific association and haplotype association analyses were performed. For the rs1625579 marker in MIR137 and the rs1006737 and rs4765905 markers in CACNA1C, significant differences in the allele frequencies were found between the patients and controls (p = 0.007949, p = 0.013658 and p = 0.013999, respectively), and the genotype association analysis for them suggested a similar pattern (p = 0.023167, p = 0.046623 and p = 0.047824, respectively). Further analysis of the haplotype rs1006737–rs4765905–rs882194 in CACNA1C showed significant associations with schizophrenia (corrected global p < 0.005), and two haplotypes (ACC and ACT) in the block were significantly increased in the patients. When the samples were analyzed separately by gender, we found no significant sex-specific associations in MIR137 and CACNA1C, which was similar to the results from the relevant haplotype association analysis in the female and male subgroups. We have provided new evidence supporting the association between MIR137 and CACNA1C and schizophrenia in the Han Chinese population.     

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.     

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.     

GAK rs1564282 and DGKQ rs11248060 increase the risk for Parkinson’s disease in a Chinese population

Numerous single-nucleotide polymorphisms (SNPs) such as GAK rs1564282 and DGKQ rs11248060 have been reported to be associated with the risk of Parkinson’s disease (PD) in Caucasian populations. However, this association is yet to be proven in the Chinese population. This study included 376 unrelated Han Chinese PD patients from Southwest China and 277 unrelated Chinese healthy controls from the same region. Two SNPs, namely, rs1564282 and rs11248060, were genotyped using Sequenom’s iPLEX assay. The allele frequencies and genotype distributions of the SNPs in the PD patients and controls were compared using Fisher’s exact test. Significant differences were found in the genotype distributions and allele frequencies for DGKQ rs11248060 between PD patients and controls (p = 0.0425 and p = 0.0308, respectively). Significant differences were also observed in the allele frequencies for GAK rs1564282 between PD patients and controls. No significant differences were observed in the genotype frequencies, minor allele frequency, and minor allele carrier frequencies between early-onset PD (EOPD) and controls, between late-onset PD (LOPD) and controls, and between EOPD and LOPD after conservative Bonferroni adjustment. GAK rs1564282 and DGKQ rs11248060 increase the risk for PD in Chinese patients. More related studies with a larger number of participants are needed to confirm these findings.     

SIRT2 polymorphism rs10410544 is associated with Alzheimer's disease in a Han Chinese population

Sirtuin 2 (SIRT2) is a strong protein deacetylase, which is highly expressed in central nervous system. Recently, an association between SIRT2 rs10410544 polymorphism and late-onset Alzheimer's disease (LOAD) was found in the APOEε4-negative Caucasian population. To investigate the potential association between the rs10410544 C/T polymorphism of SIRT2 and the risk of LOAD, we conducted an independent replication case–control study in a Northern Han Chinese population comprising 1133 cases and 1159 healthy controls being matched for age and gender. The results revealed that there were significant differences in genotype and allele frequencies between LOAD cases and controls (genotype P = 0.008, allele P = 0.009). When compared with the C allele, the T allele of rs10410544 demonstrated a 1.709-fold risk for developing LOAD. After stratification by apolipoprotein E (APOE) ε4-carrying status, only APOEε4 noncarriers (P = 0.035, adjusted OR = 1.656, 95% CI: 1.036–2.647) showed the relation between LOAD and SIRT2 rs10410544 T allele. This study provides the evidence that the rs10410544 C/T polymorphism of SIRT2 was associated with genetic susceptibility to LOAD in a Northern Han Chinese population.     

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.     

Association analysis of SLC6A4 and HTR2A genes with obsessive-compulsive disorder: Influence of the STin2 polymorphism

BackgroundObsessive-Compulsive Disorder (OCD) is a complex and chronic disorder characterized by recurrent thoughts and/or repetitive behaviors. Given the potent anti-obsessional effects of the so-called serotonin reuptake inhibitors, genes related to serotonergic system may be well implicated in the etiopathogenesis of OCD. The gene encoding the serotonin transporter (SLC6A4), which shows a variable number of tandem repeat (VNTR) polymorphism in intron 2 (STin2), have been previously associated with OCD. Additionally, the serotonin 2A receptor gene (HTR2A) has two polymorphisms (A-1438G - rs6311, and T102C - rs6313), which have also been overrepresented among OCD patients. Therefore, the aim of this study is to evaluate the association of these three polymorphisms with OCD, through the examination of potential sources of heterogeneity in previous studies including age of onset, sex and symptom dimensions.MethodsPolymorphisms were genotyped by Polymerase Chain Reaction (PCR) in a sample of 203 OCD patients and 205 healthy controls from Brazil.ResultsAlthough we did not observe any statistically significant association between the HTR2A gene polymorphisms and OCD or its clinical features, SLC6A4 STin2 polymorphism was significantly more common among OCD patients as compared to health controls. Further, a significant association between the STin2.12 allele and OCD, as well as a dominant effect of the STin2.12 allele in OCD was seen. Of note, late-onset (> 18 years) OCD was significantly more often seen in association with homozygosis for STin2.12 allele. No significant associations were observed with different OCD symptom dimensions.ConclusionOur results indicate an important influence of the STin2 polymorphism in OCD, but more studies are warranted to confirm these results.     

Association between DPP4 gene polymorphism and serum lipid levels in Chinese type 2 diabetes individuals

ObjectiveThe goal of the genetic investigation was to identify the associations of serum lipid levels and DPP-4 variants in Chinese type 2 diabetes patients.MethodsWe detected four variants of the DPP4 gene in 190 Chinese individuals with type 2 diabetes and tested for an association with dyslipidemia in 82 selected samples. Data including basic information, HbA1c, FPG, serum lipid parameters were collected. Statistical analysis was performed by SPSS 13.0 through ANOVA and χ² test.ResultsThe genetic polymorphism of rs4664443, rs3788979, rs7608798 and rs1558957 in Chinese type 2 diabetes were consistent with Hardy-Weinberg equilibrium. The CT genotype of rs4664443 suffered from higher serum TG (P = 0.013), LDL (P = 0.044) and ApoB (P = 0.006) levels, whereas the TT genotype of rs7608798 exhibited a lower serum TG level (P = 0.037). For rs3788979, the serum TG level (P = 0.034) and BMI (P = 0.04) were significantly different among genotypes. Moreover, serum TG and TC levels and BMI showed a positive correlation with the number unfavorable alleles, and individuals with more than two unfavorable alleles had higher TG (P = 0.004), TC (P = 0.011), and BMI (P = 0.044) values.ConclusionsThis is the first study to investigate DPP4 allelic distributions and their association with dyslipidemia in Chinese type 2 diabetes patients, which may have clinical significance.     

Association of miR-122, miR-124 miR-126 and miR-143 gene polymorphisms with ischemic stroke in the northern Chinese Han population

Abstract

Objectives: Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes can have diverse functional consequence by affecting the processing and target selection of miRNA. Recent evidence indicates that miRNA play important roles in the pathogenesis of atherosclerosis, which is a major cause of ischemic stroke (IS). The aim of this study was to clarify whether genetic variations in four miRNA genes (miR-143 rs4705342, miR-122 rs17669, miR-126 rs4636297, and miR-124 rs531564) contribute to IS susceptibility.

Methods: A case-control study was used to explore miRNA genetic polymorphisms in 567 IS patients and 552 control subjects that were frequency matched by age and gender. We genotyped four SNPs using polymerase chain reaction/ligation detection reaction.

Results: The miR-126 gene rs4636297 polymorphism was associated with decreased small vessel stroke risk (GA vs. GG: odds ratio (OR)?=?0.62, p?=?.015; GA?+?AA vs. GG: OR?=?0.637, p?=?.018; A vs. G: OR?=?0.696, p?=?.033). Using logistic regression analysis, this significant association remained after adjusting for confounding risk factors (adjusted OR?=?0.626, 95% confidence interval (CI)?=?0.426–0.921). However, the three other miRNA (miR-143 rs4705342, miR-122 rs17669, and miR-124 r531564) were not associated with IS risk under allele or genotype, nor in different inheritance models. In addition, there were no significant associations with stroke subtypes for these three miRNA SNPs.

Conclusion: Our study suggests that the miR-126 gene rs4636297 polymorphism may play an important role in the pathogenesis of small vessel occlusive stroke in the northern Chinese Han population.     

GABRG2 rs211037 polymorphism and epilepsy: A systematic review and meta-analysis

PurposeThe gamma-aminobutyric acid A receptor, gamma 2 (GABRG2) gene encodes the GABRγ2 protein, which has been implicated in susceptibility to epilepsy. Several studies have examined a possible link between the exonic GABRG2 rs211037 locus and susceptibility to febrile seizure (FS) and idiopathic generalized epilepsy (IGE), however results have been inconclusive. We therefore performed a systematic review and meta-analysis to examine whether this polymorphism is associated with FS or IGE.MethodsEight studies comprising 1871 epilepsy patients and 1387 controls, which evaluated association of the GABRG2 rs211037 polymorphism with susceptibility to epilepsy, were included in this meta-analysis. Meta-analysis was carried out separately for FS and IGE.ResultsMeta-analysis showed a significant association between this polymorphism and susceptibility to FS in a codominant (TT vs. CC, OR 0.47, 95% CI 0.30–0.73, p = 0.0008 and TT vs. CT, OR 0.59, 95% CI 0.42–0.83, p = 0.003) and dominant (OR 0.54, 95% CI 0.39–0.75, p = 0.0002) genetic models, influenced by two studies with small sample size. Neither allele nor genotype association was observed with IGE.ConclusionThis study showed significant association of GABRG2 rs211037 with susceptibility to FS, caused by two studies with small sample sizes, however the possibility of false positive results due to the effect of significant studies for FS cannot be excluded. Future studies with larger sample sizes of these patients are suggested to verify the results.     

TCRA, P2RY11, and CPT1B/CHKB associations in Chinese narcolepsy

ObjectivesPolymorphisms in the TCRA and P2RY11, two immune related genes, are associated with narcolepsy in Caucasians and Asians. In contrast, CPT1B/CHKB polymorphisms have only been shown to be associated with narcolepsy in Japanese, with replication in a small group of Koreans. Our aim was to study whether these polymorphisms are associated with narcolepsy and its clinical characteristics in Chinese patients with narcolepsy.MethodsWe collected clinical data on 510 Chinese patients presenting with narcolepsy/hypocretin deficiency. Patients were included either when hypocretin deficiency was documented (CSF hypocretin-1 ? 110 pg/ml, n = 91) or on the basis of the presence of clear cataplexy and HLA-DQB110602 positivity (n = 419). Genetic data was compared to typing obtained in 452 controls matched for geographic origin within China. Clinical evaluations included demographics, the Stanford Sleep Inventory (presence and age of onset of each symptom), and Multiple Sleep Latency Test (MSLT) data.ResultsChinese narcolepsy was strongly and dose dependently associated with TCRA (rs1154155C) and P2RY11 (rs2305795A) but not CPT1B/CHKB (rs5770917C) polymorphisms. CPT1B/CHKB polymorphisms were not associated with any specific clinical characteristics. TCRA rs1154155A homozygotes (58 subjects) had a later disease onset, but this was not significant when corrected for multiple comparisons, thus replication is needed. CPT1B/CHKB or P2RY11 polymorphisms were not associated with any specific clinical characteristics.ConclusionsThe study extends on the observation of a strong multiethnic association of polymorphisms in the TCRA and P2RY11 with narcolepsy, but does not confirm the association of CPT1B/CHKB (rs5770917) in the Chinese population.     

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 polymorphisms of Chinese patients with ischemic stroke and concurrent stenoses of extracranial and intracranial vessels

The etiology of concurrent stenoses of extracranial and intracranial vessels in patients with ischemic stroke is poorly understood, but hereditary factors are believed to be important. We aimed to determine whether genetic polymorphisms affecting homocysteine and lipid metabolism are associated with concurrent stenoses. The genotypes of 191 Han Chinese patients with acute ischemic stroke, of whom 47 (25%) had concurrent stenoses, and 167 healthy control patients in Hong Kong were examined for the following polymorphisms: paraoxonase 1 (PON1) Q192R, methylenetetrahydrofolate reductase (MTHFR) A222V, glutamate-cysteine ligase catalytic-subunit (GCLC)-129C > T, and oxidized low-density lipoprotein receptor (OLR) 3′ untranslated region C > T (rs1050283). The genotype distributions of PON1 Q192R and MTHFR A222V, which affect lipid and homocysteine metabolism, differed significantly between patients with stroke and healthy controls. The presence of at least one R allele in PON1 Q192R and a TT allele in OLR rs1050283 were associated with concurrent stenoses. We also identified a possible association between the presence of at least one V allele in MTHFR A222V and concurrent stenoses. This study shows that genetic polymorphisms affecting homocysteine and lipid metabolism are possible risk factors for stroke and concurrent stenoses.