Association Between Neurotensin Receptor 1 (NTR1) Gene Polymorphisms and Schizophrenia in a Han Chinese Population

Neurotensin (NT) is a multifunctional gut hormone, neurotransmitter, and neuromodulator that triggers many physiological responses by binding to the high-affinity neurotensin receptor 1 (NTR1). Previous studies have implicated the roles of NT and NTR1 in the etiology or expression of schizophrenia. This case–control study examined the associations between schizophrenia and three NTR1 gene polymorphisms (rs6090453C/G, rs6011914C/G, and rs2427422A/G) previously linked to working memory performance in a Han Chinese population. These three polymorphisms were genotyped in 390 schizophrenic patients and 565 healthy subjects. Compared with those of the controls, the frequencies for C allele in the rs6090453C/G polymorphism were higher in the schizophrenic patients (p?=?0.049) and their female subgroup (p?=?0.014). The frequencies for the rs6090453C/rs6011914G/rs2427422G (CGG) haplotype were also higher in the patients (p?=?0.016) and their female subgroup (p?=?0.005). Moreover, in the female subgroup, the frequencies for the rs6090453G/rs6011914C/rs2427422G (GCG) haplotype were higher in the controls (p?=?0.028). Our results suggest that the C allele (CC or CG genotype) in the rs6090453C/G polymorphism and the CGG haplotype may enhance schizophrenia susceptibility in the Han Chinese population, while the GCG haplotype may be a protective factor, particularly in females.     

Preliminary study of personality traits in Chinese lung cancer patients: Modification by neurotensin receptor 1 polymorphisms

This study recruited 148 lung cancer patients and 157 healthy Chinese individuals to evaluate the personality traits of Chinese lung cancer patients using the Tridimensional Personality Questionnaire and to investigate the associations between these traits and the rs6090453C/G and rs6011914C/G polymorphisms of the neurotensin receptor 1 gene. The results demonstrated significant differences in the Tridimensional Personality Questionnaire total and subscale scores between the 2 groups. Significant differences were found in the reward dependence 2 (RD2) score between the rs6090453C/G genotypes and in the total harm avoidance (HA), HA1, HA2, HA4, and RD2 scores between the rs6011914C/G genotypes. Thus, patients with lung cancer have specific personality traits, and variations in the neurotensin receptor 1 gene may be involved in the biological mechanisms of the HA and RD personality traits.     

Genetic Polymorphisms in Pre-microRNAs and Risk of Ischemic Stroke in a Chinese Population

Ischemic stroke is considered to be a complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. MicroRNAs participated in various physiopathological processes; common single-nucleotide polymorphisms (SNPs) in pre-miRNAs have been shown to be associated with susceptibility to several human diseases. We evaluated the associations of the hsa-mir-196-a2/rs11614913 T/C, hsa-mir-146a/rs2910164 C/G, and hsa-mir-499/rs3746444 A/G polymorphisms in pre-miRNAs with the risk of ischemic stroke in a Chinese population. The three polymorphisms were identified in 296 ischemic stroke patients and 391 healthy controls using polymerase chain reaction–restriction fragment length polymorphism. The frequency of the allele G of hsa-mir-499/rs3746444 A/G showed significant association with ischemic stroke when compared with controls (OR?=?1.509, 95%CI?=?1.151–1.978, P?=?0.003). Increased ischemic stroke risks were associated with rs3746444 A/G genotypes in different genetic model (homozygote comparison: P?=?0.045, OR?=?2.084, 95%CI?=?1.019–4.262; heterozygote comparison: P?=?0.024, OR?=?1.489, 95%CI?=?1.063–2.087; dominant genetic model: P?=?0.007, OR?=?1.563, 95%CI?=?1.135–2.153). Similar results were obtained by adjusted fully risk factors. However, we failed to find any association between the alleles and genotypes of rs2910164 C/G and rs11614913 T/C SNPs and ischemic stroke, respectively (p?>?0.05). The present study provided evidence that hsa-mir-499/rs3746444 A/G polymorphism might be associated with a significantly increased risk of ischemic stroke in a Chinese population, indicating that the common genetic polymorphism in pre-microRNAs contributed to the pathogenesis of ischemic stroke.     

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.     

Genetic Variants in the Fat Mass- and Obesity-Associated (FTO) Gene are Associated with Alcohol Dependence

Variants (such as rs9939609) in the fat mass- and obesity-associated (FTO) gene have been associated with obesity, type 2 diabetes, some cancers, and alcohol consumption. This study tested the associations of 167 single-nucleotide polymorphisms (SNPs) within FTO gene with alcohol dependence (AD) using two Caucasian samples: the Collaborative Study on the Genetics of Alcoholism (COGA) sample (660 AD cases and 400 controls) and the Study of Addiction: Genetics and Environment (SAGE) sample (623 cases and 1,016 controls). Logistic regression analysis of AD as a binary trait was performed using the PLINK software. For the SAGE sample, the top three SNPs showing associations with AD were rs8062891, rs1108086, and rs1420318 (p?=?0.00088, 0.00086 and 0.00086, respectively). Two SNPs (rs12597786 and rs7204609) associated with AD in the SAGE sample (p?=?0.017 and 0.034, respectively) were replicated in the COGA sample (p?=?0.017 and 0.014, respectively). Through meta-analysis of two samples using PLINK, the top three SNPs associated with AD were rs8062891, rs12597786, and rs7204609 (p?=?0.00064, 0.00076 and 0.0011, respectively). Haplotype analysis in the SAGE sample further supported the associations with AD in single-marker analysis. In addition, we found association of rs17817449 (which has a strong linkage disequilibrium with rs9939609) with AD in the SAGE sample (p?=?0.00339). The findings provide evidence of joint intervention and prevention of AD and obesity.     

Association study of polymorphisms in the cyclooxygenase-2 gene and Alzheimer’s disease risk in Chinese

To determine if polymorphisms (?765G/C, ?1195G/A and 8473T/C) of the cyclooxygenase-2 (COX-2) gene can be associated with Alzheimer disease (AD). The frequency of the polymorphisms was determined in 244 cases and 226 controls. The results revealed that the distributions of COX-2 ?765G/C and 8473T/C polymorphisms were statistically not significant between AD cases and controls. The genotype distributions and allele frequencies of COX-2 ?1195G/A polymorphism in the cases were statistically significantly different from the controls (P < 0.05). The A/A distribution and A allele frequency were significantly lower in the AD group. COX-2 ?1195AA carriers showed a one-third lower risk of developing AD as compared to those with ?1195GG and GA genotypes (OR = 0.3, 95 % CI 0.194–0.465, P = 0.000). This study suggested that ?1195G/A polymorphism of the COX-2 gene is associated with the risk of AD, and the A allele represents a protective factor in patients with AD.     

Sortilin‐related VPS10 domain containing receptor 1 and Alzheimer's disease‐associated allelic variations preferentially exist in female or type 2 diabetes mellitus patients in southern Han Chinese

Background: Both in vitro and in vivo, overexpression of the sortilin‐related VPS10 domain containing receptor 1 (SORCS1) protein lowers amyloid‐β generation. Recent studies have shown that SORCS1 variations in intron 1 are associated with sporadic Alzheimer's disease (SAD), but the results remain inconsistent. Methods: In order to clarify the role of the SORCS1 gene in southern Han Chinese, we genotyped eight single nucleotide polymorphisms (SNP) of SORCS1 in 128 SAD patients and 92 healthy controls. Results: By dividing patients and controls according to apolipoprotein status, sex and whether they had type 2 diabetes mellitus, we found that rs7907690 C allele frequencies were significantly higher in the Alzheimer's disease (AD) patients with type 2 diabetes mellitus than in the controls (P= 0.041). Also, the rs600879 GG genotype and G allele worked as protective factors of SAD in women (GG genotype, P= 0.007; G allele, P= 0.009). In multilocus analysis, the frequency of an eight‐single nucleotide polymorphism rs601883/rs7907690/rs600879/rs17277986/rs2900717/rs10884399/rs11193170/rs4918280 CCGGACGG haplotype was significantly higher in AD patients (6.3%), especially in female AD patients (9.5%), than in the controls (0.5%) (P= 0.003; P= 0.0002). However, the CTGGACGG haplotype was significantly lower in AD patients (9.3%) than in controls (20.3%) (P= 0.001). The association remained significant even after Bonferroni correction for the number of haplotypes. Conclusion: This study provides evidence that variations in the SORCS1 gene influence susceptibility to SAD in southern Han Chinese. The genetic link between AD and SORCS1 gene variations are influenced by ethnic background, sex and whether an individual has type 2 diabetes mellitus.     

Common Variants in HLA-DRA Gene are Associated with Alcohol Dependence in Two Caucasian Samples

HLA-DRA gene polymorphisms might play an important role in alcohol dependence (AD). We examined genetic associations of 29 single-nucleotide polymorphisms (SNPs) within the HLA-DRA gene with AD using two Caucasian samples—the Collaborative Study on the Genetics of Alcoholism (COGA) sample (660 AD cases and 400 controls) and the Study of Addiction: Genetics and Environment (SAGE) sample (623 cases and 1,016 controls). Logistic regression analysis using PLINK showed that 16 SNPs were associated with AD in the COGA sample and 13 SNPs were associated with AD in the SAGE sample (p?<?0.05). The best novel signal was SNP rs2239803 associated with AD in both samples (p?=?0.000817 for the COGA sample and p?=?0.0026 for the SAGE sample, respectively) while one flanking SNP rs4935356 also showed strong association in both samples (p?=?0.00219 and 0.0026 for the COGA and SAGE samples, respectively). Furthermore, these two SNPs revealed stronger associations in meta-analysis of these two samples (p?=?8.97?×?10^?6 and 2.02?×?10^?5 for rs2239803 and rs4935356, respectively). In addition, the G-A haplotype from these two SNPs revealed a significant association with AD in both the COGA and SAGE samples (p?=?0.0007 and 0.0019, respectively). These findings highlight the novel associations with HLA-DRA that may play an important role in the etiology of AD.     

A Population-based Association Study of Casein Kinase 1 Epsilon Loci with Heroin Dependence in Han Chinese

Pharmacogenetic studies have confirmed that the genetic variant of the casein kinase 1 epsilon (Csnk1ε) gene contributes to response variability to amphetamine and methamphetamine in both mice and humans. A polymorphism in the Csnk1ε gene has been reported to be associated with heroin dependence. In this study, to identify markers contributing to the genetic susceptibility of the Csnk1ε gene to heroin dependence, we examined the potential association between heroin dependence and 14 single nucleotide polymorphisms (SNPs; rs1997644, rs135764, rs867198, rs135763, rs135757, rs6001090, rs5750581, rs1534891, rs1005473, rs3890379, rs2075984, rs2075983, rs135749, and rs135745) of the Csnk1ε gene using the MassARRAY system. Participants included 398 heroin-dependent patients and 436 healthy controls from a Han Chinese population. The result revealed a strong association between the rs135745 (3′-untranslated region) genotype distribution and heroin dependence (P?=?0.0006). The frequency of the C allele was significantly higher in the heroin-dependent patients than in the healthy controls (χ²?=?7.172, P?=?0.007, OR?=?1.426, 95 % CI?=?1.099–1.849). Further genotype and clinical phenotype correlation study of the rs135745 carriers showed that the amount of heroin self-injection was higher in patients with the GC?+?CC genotype compared to the patients with the GG genotypes (P?<?0.01). Strong linkage disequilibrium (LD) was observed in block 1, block 2, and block 3 (D′?>?0.9), whereas significant evidence of LD was not observed between these SNPs in our sample population. These findings point to a role for Csnk1ε polymorphisms in heroin dependence among the Han Chinese population and may be informative for future genetic or neurobiological studies on heroin dependence.     

Association studies of 19 candidate SNPs with sporadic Alzheimer’s disease in the North Chinese Han population

Genome-wide association studies (GWAS) identified multiple single-nucleotide polymorphisms (SNPs) that are associated with the pathogenesis of Alzheimer's disease (AD). As replication in independent studies remains the only way to validate proposed GWAS signals, we detect SNPs reported in the GWAS, in order to explore their association with sporadic AD (SAD) in the Chinese population. We analyzed genotype and allele distributions of 19 SNPs reported in GWAS in 191 SAD patients and 180 healthy controls. We found that higher frequencies of rs10868366 G and rs7019241 C carriers were observed in SAD patients compared with controls (rs10868366 G: P?=?0.026, odds ratio (OR)?=?1.4, 95% confidence intervals (CI) 1.0-1.9; rs7019241 C: P?=?0.019, OR 1.4, 95% CI 1.6-1.9). Furthermore, rs10868366 G/T and rs7019241 C/T in GOLPH2 were in strong linkage disequilibrium and formed a relative protective factor rs10868366 T/rs7019241 T and a relative risk factor rs10868366 G/rs7019241 C. For SNP rs3826656 in near gene 5' region of CD33, the results revealed that in subjects with APOE ε4 alleles, the A allele was associated with a reduced risk of SAD compared with the G allele (OR 0.479; 95% CI 0.263-0.870, P?=?0.015), and AA genotype was associated with a reduced risk of SAD compared with the genotype AG?+?GG (OR 0.395; 95% CI 0.158-0.659, P?=?0.008). Our results support the view that rs10868366 and rs7019241 in GOLPH2 and rs3826656 in near gene 5' region of CD33 are significantly associated with SAD in the north Chinese Han population.     

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.     

Association of Single-Nucleotide Polymorphisms in the Cannabinoid Receptor 2 Gene with Schizophrenia in the Han Chinese Population

Cannabinoid receptor 2 (CNR2) is a major receptor in the endogenous cannabinoid system. In recent years, many studies have shown that the receptor is closely associated with schizophrenia. This study examined the relationship between CNR2 gene polymorphisms (rs2501432C/T, rs2229579C/T, rs2501401G/A) and schizophrenia. Three hundred sixteen schizophrenia patients and 334 healthy subjects were recruited as case and control groups, respectively. For rs2501432, the CT/TT genotype frequencies in the dominant model, TT genotype frequencies in the additive model, and T allele frequencies of the case group were lower than the control (P?<?0.05), and the CT and TT genotypes and T allele frequencies of the male case group were significantly lower than the control (P?<?0.05). For rs2229579, the T allele frequencies of the case group were higher than the control (P?<?0.05). The T-C-G haplotype in the case group had a significantly lower frequency compared with the controls, but the T-T-A haplotype frequencies were higher in the case group than in the controls (P?<?0.05). Our results suggest that the T allele of rs2501432 may be a protective factor, particularly in males, but the T allele of rs2229579 may be a risk factor for schizophrenia. T-C-G may be a protective haplotype for schizophrenia, but not the T-T-A haplotype.     

胰岛素样生长因子1、载脂蛋白酶E基因多态性与阿尔茨海默病关系的研究

目的探讨河南省汉族人群胰岛素样生长因子1(insulin like growth factor 1,IGF-1)基因rs972936位点多态性、载脂蛋白酶E(Apo E)基因多态性与阿尔茨海默病(Alzheimer’s disease,AD)之间的相关性。方法选取58例AD患者和126例年龄、性别相匹配的健康对照(ND)者为研究对象,柱层析法提取外周血基因组DNA,采用PCR和基因测序技术检测IGF-1基因rs972936位点及Apo E基因型多态分布,并进行对比分析。结果与ND组比较,AD组IGF-1基因rs972936位点3种基因型分布总体差异有统计学意义(χ~2=6.108,P=0.047),其中AD组中GG基因型的频率高于对照组(70.7%51.6%,χ~2=5.935,P=0.015),G等位基因频率明显高于健康对照组(χ~2=6.502,P=0.011);AD组Apo Eε4等位基因频率可能增加AD的患病风险(OR=2.872,95%CI 1.542~5.351)(P=0.001);Apo Eε4等位基因不影响IGF-1基因rs972936位点的基因型或等位基因的分布频率(P0.05)。结论 IGF-1基因rs972936位点多态性与河南汉族人群AD的发病可能有相关性,其中GG基因型、G等位基因可能是AD发病的独立于Apo Eε4等位基因的危险因素。Apo Eε4等位基因是散发性AD的主要危险因素。     

ApoA1, ApoJ and ApoE Plasma Levels and Genotype Frequencies in Cerebral Amyloid Angiopathy

The involvement of apolipoproteins, such as the ApoE4 isoform, in Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA) highlights the fact that certain lipid carriers may participate in soluble β-amyloid (Aβ) transport. Our general aim was to characterize the soluble levels of the apolipoproteins apoE, apoA1 and apoJ/clusterin and their genotype status in patients with CAA. We analyzed the genotypes frequency of APOA1 (rs5069, rs670), CLU (rs11136000, rs1532278, rs7012010, rs9331888) and APOE (rs429358, rs7412) in a cohort of patients with CAA-associated intracerebral hemorrhage (ICH) (n = 59) and compared the results with those from hypertension-associated ICH (n = 42), AD patients (n = 73) and controls (n = 88). In a subgroup of patients, we also determined the plasma concentrations of apoE, apoA1 and apoJ/clusterin. We found increased plasma apoJ/clusterin levels in CAA patients compared to AD patients or controls after adjusting for sex and age (CAA vs. controls, p = 0.033; CAA vs. AD, p = 0.013). ApoA1 levels were not altered between groups, although a strong correlation was observed between plasma Aβ(1-40) and apoA1 among CAA patients (r = 0.583, p = 0.007). Regarding plasma apoE concentration, a robust association between circulating levels and genotype status was confirmed (p < 0.001). Whereas the APOE4 frequency was higher in AD (p < 0.001) and CAA (p = 0.013), the APOA1 and CLU genotypes were not different among groups. In the CAA cohort, the risk-linked CLU variant (C) rs11136000 was associated with white matter hyperintensities (p = 0.045) and the presence of lobar microbleeds (p = 0.023) on MRI. In summary, our findings suggest that apoA1 may act as a physiological transporter of Aβ(1-40) and that apoJ/clusterin appears to be a chaperone related to distinctive lesions in CAA brains.     

囊泡相关膜蛋白8基因多态性与动脉粥样硬化性脑梗死相关性研究

目的探讨囊泡相关膜蛋白8(VAMP8)基因rs13426038和rs10666612多态性与动脉粥样硬化性脑梗死(ACI)的相关性。方法采用聚合酶链反应-限制性片段长度多态性技术,对动脉粥样硬化性脑梗死组和正常对照组VAMP8基因rs13426038和rs10666612位点进行基因分型。结果两位点基因型分布均符合Hardy-Weinberg遗传平衡检验。VAMP8基因rs13426038位点CC/GG基因型频率在ACI组和对照组分别为20.5%/35.9%和15.0%/36.0%,C/G等位基因频率为42.3%/57.7%和39.5%/60.5%;两组间基因型及等位基因频率差异比较无统计学意义(P=0.08,P=0.25)。VAMP8基因rs10166612位点AA/GG基因型频率在ACI组和对照组分别为92.7%/0.5%和91.8%/0%,A/G等位基因频率为96.1%/3.9%和95.9%/4.1%;两组间基因型及等位基因频率分布比较亦无统计学差异(P=0.16,P=0.46)。结论 VAMP8基因rs13426038 C/G和rs10166612 A/G多态性可能与ACI发生无关。     

Lack of association between the <Emphasis Type="Italic">Angiogenin</Emphasis> (<Emphasis Type="Italic">ANG</Emphasis>) rs11701 polymorphism and amyotrophic lateral sclerosis risk: a meta-analysis

To perform a meta-analysis to help resolve the controversy of whether the Angiogenin (ANG) rs11701 polymorphism is associated with amyotrophic lateral sclerosis (ALS) risk. A literature search of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, Wanfang and SinoMed was conducted for eligible studies published up to Jun 5, 2015. The strength of the association between the polymorphism and ALS susceptibility was estimated by odds ratio (OR) and associated 95 % confidence interval (CI). The pooled ORs were assessed for the dominant model (TG + GG vs. TT), recessive model (GG vs. TG + TT), heterozygote model (TG vs. TT), homozygote model (GG vs. TT) and allele model (G vs. T). Ten eligible articles were identified, which reported 14 case–control studies and a total of 5807 cases and 3861 controls. Analysis of pooled ORs and 95 % CIs suggested lack of association between the ANG rs11701 polymorphism and risk for ALS, Familial ALS or Sporadic ALS (all p value for z test >0.05). A stratified analysis according to Caucasian or Han Chinese origin further showed that the rs11701 polymorphism was not associated with the disease risk in Caucasians or Han Chinese. There is no difference in the polymorphism frequencies between patients with FALS or SALS. The ANG rs11701 polymorphism was not associated with risk for ALS, FALS or SALS. There is no difference between the polymorphism frequencies in patients with FALS or SALS. Further well-designed studies with larger populations are required to validate these results.     

NRG3 gene is associated with the risk and age at onset of Alzheimer disease

The Neuregulin 3 (NRG3) gene at 10q22–q24 has been implicated in multiple psychiatric traits such as cognitive impairment. We therefore hypothesized that NRG3 gene polymorphisms may play a role in Alzheimer disease (AD). This present study explored the association of NRG3 with the age at onset (AAO) of AD and the risk of developing AD. Secondary data analysis of 257 single-nucleotide polymorphisms (SNPs) in NRG3 gene was performed in 806 Alzheimer’s disease patients and 782 controls using logistic regression and linear regression analyses. Eight SNPs were associated with the risk of AD (p < 0.05), while linear regression analysis showed 33 SNPs associated with the AAO of AD (p < 0.05). Two-SNP haplotype analyses based on UNPHASED revealed that the G–C haplotype from rs17685233 and rs17101017 was significantly associated with AD (p = 0.0031) and the A–G haplotype from rs504522 and rs474018 as well as the A–G haplotype from rs504522 and rs2483295 were more significantly associated with the AAO of AD (p = 6.72 × 10^?5). Using an independent family-based sample, we found one SNP rs11192423 associated with AAO both in the case–control sample (p = 0.0155) and in the family sample (p = 0.0166). In addition, we observed nominally significant associations with AD and AAO for several flanking SNPs (p < 0.05). This is the first study demonstrating that genetic variants in the NRG3 gene play a role in AD. Our results also revealed that SNPs in the NRG3 genes were more strongly associated with AAO of AD.     

GWAS-Supported <Emphasis Type="Italic">CRP</Emphasis> Gene Polymorphisms and Functional Outcome of Large Artery Atherosclerotic Stroke in Han Chinese

Elevated C-reactive protein (CRP) levels increase the risk of poor functional disability in patients with ischemic stroke (IS). This study aimed to investigate the association between CRP gene polymorphisms and 3-month functional disability of large artery atherosclerotic (LAA) stroke in Han Chinese. Patients with first-ever LAA IS were prospectively enrolled in Nanjing Stroke Registry Program between August 2013 and October 2015. Five single-nucleotide polymorphisms (SNPs) (rs876537, rs2794520, rs3093059, rs7553007 and rs11265260) in CRP gene related to CRP levels in Asian by genome-wide association study were genotyped. The functional outcome at 3 months after the index stroke was assessed by the modified Rankin scale. Associations between genotypes and functional outcome of LAA IS were analyzed with logistic regression model. A total of 690 eligible patients (507 males) were evaluated. SNPs rs11265260 (multivariate-adjusted, p?=?0.022), rs2794520 (multivariate-adjusted, p?=?0.036) and rs3093059 (multivariate-adjusted, p?=?0.027) were significantly associated with elevated CRP in acute IS. Two SNPs, rs3093059 (dominant model: adjusted OR 2.49; 95% CI 1.55–4.00; recessive model: adjusted OR 3.67; 95% CI 1.22–11.03) and rs11265260 (dominant model: adjusted OR 2.51; 95% CI 1.56–4.02; recessive model: adjusted OR 4.70; 95% CI 1.63–13.56) independently predicted 3-month poor outcome of first-ever LAA IS, after adjusting for covariates. In addition, haplotype analysis indicated that haplotype GCTGC (adjusted OR 1.76; 95% CI 1.05–2.95; p?=?0.031) increased the poor outcome risk. SNPs rs3093059 and rs11265260 in CRP gene may influence the 3-month functional outcome of first-ever LAA IS in Han Chinese.     

<Emphasis Type="Italic">PEMT</Emphasis> G523A (V175M) Is Associated with Sporadic Alzheimer's Disease in a Chinese Population

There is evidence that increased concentrations of circulating homocysteine are associated with Alzheimer's disease (AD). Phosphatidylethanolamine N-methyltransferase (PEMT) is an important catalyst involved in the production of homocysteine. We investigated the association of a functional single nucleotide polymorphism (rs7946) in PEMT with sporadic AD risk in a Han Chinese population that included 386 AD patients and 366 controls. PEMT G523A was genotyped by either sequencing or PCR-restriction fragment length polymorphism analysis. The plasma homocysteine concentrations of 210 subjects were determined by high-performance liquid chromatography. Significant higher frequency of the A allele was detected in AD cases than in controls (A vs. G, p = 0.007, OR = 1.482, 95% CI 1.114–1.972). After adjusting for gender, age/age at onset, and APOE ε4 status, logistic analysis showed rs7946 was associated with AD in a dominant model (AA + GA vs. GG, p = 0.007, OR = 1.596, 95% CI 1.138–2.240). When stratified by APOE ε4 status or gender, the significant difference was only observed in the APOE ε4 non-carriers and in the female subjects, respectively. We did not find a relationship of this polymorphism with plasma homocysteine levels. These results suggested that PEMT G523A is associated with AD and that the A allele is an APOE ε4-independent risk factor for AD among Han Chinese women.