Genome-wide association study identifies RBFOX1 locus influencing brain glucose metabolism.

BACKGROUND: Fluorodeoxyglucose f18 positron emission tomography (18F-FDG PET) is regarded as the only functional neuroimaging biomarker for degeneration which can be used to increase the certainty of Alzheimer's disease (AD) pathophysiological process in research settings or as an optional clinical tool where available. Although a decline in FDG metabolism was confirmed in some regions known to be associated with AD, there was little known about the genetic association of FDG metabolism in AD cohorts. In this study, we present the first genome-wide association study (GWAS) analysis of brain FDG metabolism. METHODS: A total of 222 individuals were included from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) cohort. All subjects were restricted to non-Hispanic Caucasians and met all quality control (QC) criteria. Associations of 18F-FDG with the genetic variants were assessed using PLINK 1.07 under the additive genetic model. Genome-wide associations were visualized using a software program R 3.2.3. RESULTS: One significant SNP rs12444565 in RNA-binding Fox1 (RBFOX1) was found to have a strong association with 18F-FDG (P=6.06×10-8). Rs235141, rs79037, rs12526331 and rs12529764 were identified as four suggestive loci associated with 18F-FDG. CONCLUSIONS: Our study results suggest that a genome-wide significant SNP (rs12444565) in the RBFOX1, and four suggestive loci (rs235141, rs79037, rs12526331 and rs12529764) are associated with 18F-FDG.

Association of lectin-like oxidized low density lipoprotein receptor 1 (OLR1) polymorphisms with late-onset Alzheimer disease in Han Chinese.

BACKGROUND: Lectin-like oxidized low density lipoprotein receptor 1 (OLR1) locates within the area of chromosome 12p, which has been identified as the AD-susceptible region, and plays a role in lipid metabolism. Therefore, it has been suggested to be a good candidate gene for Alzheimer's disease (AD). Several SNPs within OLR1 have been reported to have association with AD among Caucasians. METHODS: We selected and genotyped three SNPs (rs1050283, rs1050286, rs17808009) in OLR1 to investigate its possible relationship with the onset of late-onset Alzheimer disease(LOAD) in 984 LOAD cases and 1,354 healthy controls among northern Han Chinese. RESULTS: No significant association was found between the OLR1 (rs1050283, rs1050286, rs17808009) polymorphisms and LOAD, even after adjustment for gender and age and stratification for apolipoprotein E (APOE) status. CONCLUSIONS: Our study showed that the SNPs (rs1050283, rs1050286, rs17808009) located in the 3'UTR of OLR1 may not involve in the mechanism of LOAD in Han Chinese population.

First flush of storm runoff pollution from an urban catchment in China.

Storm runoff pollution process was investigated in an urban catchment with an area of 1.3 km2 in Wuhan City of China. The results indicate that the pollutant concentration peaks preceded the flow peaks in all of 8 monitored storm events. The intervals between pollution peak and flow peak were shorter in the rain events with higher intensity in the initial period than those with lower intensity. The fractions of pollution load transported by the first 30% of runoff volume (FF30) were 52.2%-72.1% for total suspended solids (TSS), 53.0%-65.3% for chemical oxygen demand (COD), 40.4%-50.6% for total nitrogen (TN), and 45.8%-63.2% for total phosphorus (TP), respectively. Runoff pollution was positively related to non-raining days before the rainfall. Intercepting the first 30% of runoff volume can remove 62.4% of TSS load, 59.4% of COD load, 46.8% of TN load, and 54.1% of TP load, respectively, according to all the storm events. It is suggested that controlling the first flush is a critical measure in reduction of urban stormwater pollution.

PGRN Is Associated with Late-Onset Alzheimer's Disease: a Case-Control Replication Study and Meta-analysis.

Progranulin (PGRN) plays an important role in Alzheimer's disease (AD) through participating in altering neurite outgrowth and neuronal survival. Previous studies identified that rs5848 in the 3'-untranslated region (3'-UTR) of the PGRN gene (GRN) is strongly associated with AD in Caucasians. In order to assess the involvement of the GRN polymorphism in the risk of late-onset AD (LOAD), we analyzed the genotype and allele distributions of rs5848 in 2350 Han Chinese subjects (AD, 992; control, 1358). The minor T allele of rs5848 was significantly associated with an increased risk of LOAD (P = 0.005, odds ratio (OR) = 1.197, 95 % confidence interval (CI) = 1.057-1.355). Moreover, the association was further validated in the multivariate logistic regression analysis (dominant model: OR = 1.195, P = 0.038, recessive model: OR = 1.386, P = 0.025; additive model: OR = 1.187, P = 0.009). Interestingly, we observed that the interaction between apolipoprotein E (APOE) and rs5848 significantly altered the risk for AD. The rs5848 polymorphism was only significantly associated with LOAD in APOE ε4 allele carriers. Then we included five studies (including the present study) and conducted a meta-analysis which consisted of 3236 cases (male, 1152; female, 2084) and 3405 (male, 1436; female, 1969) controls. The result of the meta-analysis supported T allele of rs5848 within GRN as a risk factor for AD. In conclusion, our results demonstrated that rs5848 polymorphism within GRN was associated with LOAD.

Association of DISC1 Polymorphisms with Late-Onset Alzheimer's Disease in Northern Han Chinese.

The disrupted-in-schizophrenia-1 (DISC1) is a candidate gene for psychiatric diseases and plays various roles in brain development. It has been reported as a candidate gene for Alzheimer's disease (AD) in a recent large genome-wide association study in Caucasians. To explore the associations between DISC1 and AD, we performed a case-control study including 2318 subjects in Northern Han Chinese. We found that one single nucleotide polymorphism (rs6675281) was associated with the risk of late-onset Alzheimer's disease (LOAD) in northern Han Chinese population. As for rs821616 and rs3738401, no association was detected with LOAD. In conclusion, DISC1 increased the risk for LOAD in northern Han Chinese population.

Associations of rs3740677 within GAB2 Gene with LOAD in Chinese Han Population.

GRB2-associated binding protein 2 (GAB2) has been identified as a crucial factor in Alzheimer's disease (AD), and ten common variants within GAB2 have been detected to be associated with AD onset risk in genome-wide association studies (GWAS). Here, we first screened a common locus (rs3740677) in 3' UTR of GAB2 sequence which is targeted by the miRNA-185 and initiatively explored the probable associations of rs3740677 with risk for late-onset AD (LOAD) in a large scale case-control study from Chinese Han populations (992 LOAD patients and 1358 healthy subjects). Eventually, the genotype (P = 0.024) and allele (P = 0.008) distribution of rs3740677 showed significant difference between LOAD and control group, and we observed a significant association of T allele in rs3740677 with LOAD risk in multivariate analysis and it decreased the risk for LOAD (dominant: OR = 0.831, 95 % CI = 0.702-0.983, P = 0.031; additive: OR = 0.855, 95 % CI = 0.745-0.983, P = 0.027) adjusted for age, gender, and APOE ε4 status. Our study further confirmed the association of GAB2 and AD. However, the absolute and correct association of rs3740677 with AD still required more investigations in diverse regions and ethnics.

SORL1 Is Associated with the Risk of Late-Onset Alzheimer's Disease: a Replication Study and Meta-Analyses.

The sorting-related receptor gene (SORL1) has been defined as an interesting candidate gene for Alzheimer's disease (AD). Recently, one novel variant, rs11218343, within SORL1 was reported to be related to late-onset Alzheimer's disease (LOAD) in Caucasians, Korean, and Japanese. The aim of this case-control study is to investigate whether SORL1 rs11218343 contributes to susceptibility for LOAD in Chinese. Furthermore, our data, along with previously studies, were pooled for determining the risk of the rs11218343 polymorphism on LOAD. The rs11218343 polymorphism was genotyped in the 2350 independent subjects from Northern Han Chinese population (including 992 cases and 1358 age- and gender-matched controls). Result of the case-control study showed the association between rs11218343 polymorphism and the risk of LOAD in a Northern Han Chinese population (recessive model: odds ratio (OR) = 0.641, 95 % confidence interval (CI) = 0.464-0.884, P = 0.007; additive model: OR = 0.873, 95 % CI = 0.765-0.996, P = 0.043). The results of meta-analysis in subgroups (Caucasian and Asian) and the whole showed that the minor allele (C allele) within rs11218343 played a protective effect on AD risk (OR (95 % CI), 0.77 (0.72-0.83), 0.85 (0.79-0.91), 0.81 (0.76-0.85), respectively). In conclusion, the C allele in SORL1 rs11218343 may be a protective factor for LOAD in both Caucasian and Han Chinese.

INPP5D rs35349669 polymorphism with late-onset Alzheimer's disease: A replication study and meta-analysis.

Inositol polyphosphate-5-phosphatase (INPP5D) was reported to be associated with Alzheimer's disease (AD) through modulating the inflammatory process and immune response. A recent genome-wide association study discovered a new locus single nucleotide polymorphism (SNP, rs35349669) of INPP5D which was significantly associated with susceptibility to late-onset Alzheimer's disease (LOAD) in Caucasians. In this study, we investigated the relations between the INPP5D polymorphism rs35349669 and LOAD in Han Chinese population comprising 984 LOAD cases and 1352 healthy controls being matched for age and gender. Our results showed no obvious differences in the genotypic or allelic distributions of rs35349669 polymorphism between LOAD cases and healthy controls (genotype: p = 0.167; allele: p = 0.094). Additionally, when these data were stratified by APOEε4 status, there are still no evident differences in the genotypic or allelic distributions in APOEε4 carriers (p > 0.05). Furthermore, meta-analysis of 81964 individuals confirmed that rs35349669 was significantly associated with the risk for LOAD (OR=1.08, 95%CI=1.06-1.11), but the results remained negative in Chinese subgroup (OR=0.77, 95%CI=0.53-1.13). Overall, the current evidence did not indicate that INPP5D rs35349669 polymorphism play a role in the genetic predisposition to LOAD in Chinese population.

MEF2C rs190982 polymorphism with late-onset Alzheimer's disease in Han Chinese: A replication study and meta-analyses.

The myocyte enhancer factor (MEF2) family of transcription factors plays a vital role in memory and learning due to its functions in regulating synapse number and reducing dendritic spines. Myocyte enhancer factor 2 C (MEF2C) is regarded as modulator of amyloid-protein precursor (APP) proteolytic processing, in which amyloid-ß (Aß) is produced. A common single nucleotide polymorphism (SNP, rs190982) in MEF2C gene was identified to be related to late-onset Alzheimer's disease (LOAD) in Caucasians in a large meta-analysis of genome-wide association studies (GWAS). Here, we recruited unrelated 984 LOAD patients and 1348 healthy controls matched for gender and age to ascertain whether the rs190982 polymorphism is related to LOAD in Han Chinese. No difference in the genotype and allele distributions of the MEF2C rs190982 polymorphism was found between LOAD cases and healthy controls (genotype: P = 0.861; allele: P = 0.862), even after stratification for APOE ε4 allele as well as statistical adjustment for age, gender and APOE ε4 status. Furthermore, the meta-analysis in 4089 Chinese individuals did not detect the association of rs190982 within MEF2C with the risk for LOAD (OR = 1.03, 95%CI = 0.90-1.18). Overall, the current evidence did not support the relation between rs190982 polymorphism within MEF2C and the LOAD risk in Northern Han Chinese.

Association of HMGCR polymorphism with late-onset Alzheimer's disease in Han Chinese.

The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) acts as a potential genetic modifier for Alzheimer's disease (AD). Previous reports identified that HMGCR rs3846662 polymorphism is associated with biosynthesis of cholesterol in AD pathology. In order to assess the involvement of the HMGCR polymorphism in the risk of late-onset AD (LOAD) in northern Han Chinese, we performed a case-control study of 2334 unrelated subjects (984 cases and 1350 age- and gender-matched controls) to evaluate the genotype and allele distributions of the HMGCR rs3846662 with LOAD. The genotype distribution (GG, AG, AA) of rs3846662 was significantly different between LOAD patients and controls (P = 0.003), but the allele distribution did not reach a significant difference (P = 0.614). After adjusting for age, gender and the APOE ε4 status, the minor A allele of rs3846662 was validated as a protective factor for LOAD in dominant model (OR = 0.796, P = 0.02, 95% CI = 0.657-0.965). Interestingly, we observed rs3846662 polymorphism was only significantly associated with LOAD in APOE ε4 non-carriers (OR = 0.735, P = 0.005, 95% CI = [0.593, 0.912]). In conclusion, our study demonstrates A allele of HMGCR rs3846662 acts as a protective factor for LOAD in northern Han Chinese.

Common variant in PTK2B is associated with late-onset Alzheimer's disease: A replication study and meta-analyses.

Emerging evidence indicates that protein tyrosine kinase 2ß (PTK2B) is involved in the pathogenesis of Alzheimer's disease (AD). Recently, a large, two-stage meta-analysis of genome-wide association study (GWAS) confirmed that PTK2B was correlated with an increased risk of AD in Caucasian populations. The aim of this study was to investigate the association between PTK2B polymorphism rs28834970 and the risk of LOAD in a Han Chinese population. A total of 984 sporadic LOAD patients and 1,354 healthy age- and sex-matched control subjects from the Han Chinese population were included in this study. Our results showed no significant differences in the frequency of rs28834970 alleles and genotypes between AD cases and controls. However, meta-analysis of 82,513 individuals confirmed that rs2883490 within PTK2B increased the risk of LOAD (OR=1.09, 95%CI=1.07-1.12). Additionally, when these data were stratified by APOEε4 status, the difference of allele frequency was evident in APOEε4 carriers (P=0.027, OR=1.423, 95%CI=1.041-1.945), and positive associations were also observed under an additive model in APOEε4 carriers (P=0.041, OR=1.384, 95%CI=1.014-1891). In summary, our study provides that PTK2B polymorphism (rs28834970) could modify the risk of LOAD, and PTK2B polymorphism (rs28834970) and APOE may interact to increase LOAD risk in a Han Chinese population.

FERMT2 rs17125944 polymorphism with Alzheimer's disease risk: a replication and meta-analysis.

A recent meta-analysis of genome-wide association studies (GWAS) in population of Caucasian identified a single nucleotide polymorphism (SNP) rs17125944 in the FERMT2 gene as a new susceptibility locus for late-onset Alzheimer's disease (LOAD). In order to validate the association of the rs17125944 polymorphism with LOAD risk in the northern Han Chinese, we recruited a case-control study of 2338 Han Chinese subjects (984 cases and 1354 age- and gender-matched controls). Our results demonstrated that there was no significant association between the rs17125944 polymorphism and LOAD (genotype: P = 0.953; allele: P = 0.975). Furthermore, no significant differences were observed in alleles and genotypes distribution after stratification by apolipoprotein E (APOE) ε4 and multivariate logistic regression analysis. We also performed a meta-analysis in 81908 individuals. The meta-analysis showed that the C allele is the risk factor for LOAD in Caucasian group (OR = 1.15, 95 % CI = 1.10-1.20) and combined population (OR = 1.13, 95 % CI = 1.08-1.19). While in Chinese population, the C allele is not associated with increased risk of LOAD (OR = 1.07, 95 % CI = 0.89-1.28). In conclusion, our study showed that the rs17125944 polymorphism in FERMT2 gene might not be association with LOAD in northern Han Chinese population.

[Clinical observation on combination of source point and Back-Shu Point for treatment of perimenopausal syndrome].

OBJECTIVE: To observe the clinical therapeutic effect of combination of Source Point and Back-Shu Point on perimenopausal syndrome, and provide a new thought of therapy for perimenopausal syndrome. METHODS: Eighty cases of perimenopausal syndrome were randomly divided into a combination of Source Point and Back-Shu Point group and a routine acupuncture group, 40 cases in each group. The combination of Source Point and Back-Shu Point group was treated with acupuncture at Taixi (KI 3), Taichong (LR 3), Taibai (SP 3), Sanyinjiao (SP 6), Shenshu (BL 23), Ganshu (BL 18), Pishu (BL 20), Guanyuan (CV 4); and the routine acupuncture group was treated with acupuncture at Baihui (GV 20), Guanyuan (CV 4), Shenshu (BL 23), Taixi (KI 3), San-yinjiao (SP 6). The Kupperman score and the changes of serum estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were observed before and after treatment in the two groups. RESULTS: The total effective rate of 92.5% in the combination of Source Point and Back-Shu Point group was superior to 80.0% in the routine acupuncture group, with a significant difference (P < 0. 05); the Kupperman score of 24. 85 +/- 8.35 in the combination of Source Point and Back-Shu Point group was significantly decreased as compared with 35.38 +/- 9.83 in the routine acupuncture group (P < 0.05) after treatment; the contents of E2, FSH and LH in the combination of Source Point and Back-Shu Point group were significantly improved after treatment, and with a significant difference compared to the routine acupuncture group (P < 0.01, P < 0.05). CONCLUSION: Combination of Source Point and Back-Shu Point has a benign regulation function for E2, FSH and LH, and can significantly improve the Kupperman score, is superior to routine acupuncture for perimenopausal syndrome.

[Clinical observation on abdominal electroacupuncture for treatment of poststroke constipation].

OBJECTIVE: To compare therapeutic effects of abdominal electroacupuncture (EA) and western medicine on poststroke constipation. METHODS: Eighty cases were randomly divided into an EA group and a medication group, 40 cases in each group. The EA group were treated with EA at Daheng (SP 15), Fujie (SP 14), Tianshu (ST 25), Shuidao (ST 28), etc., once a day, 30 min each session, and the medication group with oral administration of 10 mg Cisapride, thrice each day. Seven days constituted one course. After 2 courses, clinical therapeutic effects were evaluated by cumulative scores of symptoms. RESULTS: The total effective rate of 92.5% in the EA group was significantly better than 72.5% in the medication group (P < 0.05). After treatment, the cumulative scores of clinical symptoms significantly decreased in the two groups (P < 0.05) and the improving degrees of symptoms in the EA group was significantly better than that in the medication group (P < 0.05). CONCLUSION: Abdominal electroacupuncture has a definite therapeutic effect on poststroke constipation, accelerating gastrointestinal movement.

[Clinical study on acupuncture combined with rehabilitation therapy for treatment of poststroke shoulder-hand syndrome].

OBJECTIVE: To observe therapeutic effect of acupuncture combined with rehabilitation therapy on poststroke shoulder-hand syndrome. METHODS: One hundred and twenty cases of poststroke shoulder-hand syndrome were randomly divided into an acupuncture-rehabilitation group, an acupuncture group and a rehabilitation group, 40 cases in each group. The acupuncture-rehabilitation group were treated with acupuncture at Jianyu (LI 15), Jianqian, Jianliao (TE 14), etc. in combination with motor therapy (rehabilitation training), the acupuncture group with simple acupuncture therapy, and the rehabilitation group with simple motor therapy. Upper extremity motor function, pain, joint activity were used for assessment of therapeutic effects. RESULTS: The total effective rate of 87.5% in the acupuncture-rehabilitation group was significantly better than 67.5% in the acupuncture group and 65.0% in the rehabilitation group (P<0.01); acupuncture combined with rehabilitation therapy could significantly improve upper limb motor function, pain and joint activity with very significant differences as compared with the acupuncture group and the rehabilitation group (P<0.01). CONCLUSION: Acupuncture combined with rehabilitation therapy has a high cured rate and an obvious therapeutic effect on poststroke shoulder-hand syndrome.

[Effect of antecedent dry weather period on urban storm runoff pollution load].

Twelve storm events were surveyed at Shilipu catchment in Wuhan City through three-year monitoring regime. The flow discharges, total suspended solids (TSS), chemical oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP) in runoff were measured to study the mechanism of urban stormwater runoff pollution. The relationship between the event pollution load and the antecedent dry weather period was identified to discuss the influence of the urban surface sanitation management, operation of sewer pipe maintenance and rainfall characteristics on the urban stormwater runoff pollution. It was found that the antecedent dry weather period and runoff amount were the important determining factors in the generation of urban stormwater runoff pollution. The event pollution load was positively correlated to the antecedent dry weather period between two rainfall events (R2 = 0.95, p < 0.01). It was the most important hydrological factor influencing the events pollution loads. The best regression equation to estimate pollution load for storm events was developed based on the antecedent dry weather period and runoff depth. Source control including improving urban street sweeping activities and operation of sewer pipe maintenance should be made to reduce the amount of available pollutant over the dry days. It is important alternative to control urban stormwater runoff pollution for Hanyang District.