Study on value-based medical insurance access and pricing methods of multi-indication drugs / 中国药房

OBJECTIVE To discuss medical insurance access and pricing methods for multi-indication drugs. METHODS The access situation of multi-indication drugs in China’s medical insurance negotiation over the years was sorted out. Referring to the economic theory of value-based pricing and the relevant experience of other countries， five applicable pricing methods of 3 categories for multi-indication drug in China were summarized. Taking ceftazidime-avibactam（CAZ-AVI） as an example， cost- utility analyses were performed for different indications， and appropriate pricing methods were applied. RESULTS & CONCLUSIONS All multi-indication drugs in China adopted a single pricing method. The pricing methods that could be explored include product-based pricing， such as single pricing based on the lower-value indication or mixed/weighted single pricing； indication-based pricing， such as developing a new agreement for single pricing under different discounts and listing with different brands and pricing of the same medicine for different indications； and compensation for access restrictions. Each method has its advantages and limitations. The case of CAZ-AVI showed that it is necessary to estimate the value of each indication for multi- indication drugs， and comprehensively consider appropriate access conditions and pricing methods based on value. Although single pricing is simple to operate， it is different to reflect the value entirely. The indication-based pricing and compensation for access restrictions all depend on the information collection system and the cooperation of multiple departments. China is supposed to carry out the value-based pricing of multi-indication drugs and constantly explore reasonable access methods to improve overall social welfare.

Economic Evaluation of Dexamethasone Combined with Rituximab for the First-line Treatment of Chronic Primary Immune Thrombocytopenia in Adults / 中国药房

OBJECTIVE：To evaluate the economy performance of dexamethasone （DXM）combined with rituximab （RTX） for the first-line treatment of chronic primary immune thrombocytopenia （ITP）in adults. METHODS ：From the perspective of China ’s medical and health system ，Markov model for eight states was constructed with a period of 4 weeks and a time limit of 20 years， using DXM regimen as control. The cost-utility of DXM+RTX regimen for the treatment of chronic ITP in adults were evaluated. The parameters of clinical efficacy and utility value were derived from own published literature ；cost parameters were from the MENET website and the official websites of local health committees and medical insurance bureaus ；one-way sensitivity analysis ， probability sensitivity analysis and scenario analysis were performed to observe the uncertainty of model and data source. RESULTS：The average cost of DXM+RTX regimen was 51 064 dollars and that of DXM regimen was 50 455 dollars. Compared with DXM regimen ，DXM+RTX regimen yielded an additional 0.14 QALYs for each patient ；the incremental cost-effectiveness ratio（ICER）was 4 356 dollars/QALY，and was lower than the willingness-to-pay threshold of China ’s per capita gross domestic product（GDP）in 2020. In the one-way sensitivity analysis ，the cost of drugs was the main driver in the model. Probability sensitivity analysis demonstrated that DXM+RTX regimen had 57.5％-61.0％ probability of being cost-effective at a willingness- to-pay threshold of 1-3 times per capita GDP in 2020. The results of scenario analysis showed that DXM+RTX regimen would have obvious long-term benefits ，and the utility value had little impact on the conclusion. CONCLUSIONS ：DXM + RTX is more economical than DXM in the treatment of chronic ITP in adults ，but the results have the uncertainty.

Systematic Review of Cost-utility Analysis Methodology for PD- 1/PD-L1 Inhibitors in the Treatment of Non- small Cell Lung Cancer / 中国药房

OBJECTIVE：To provide reference for impro ving the quality of programmed cell death protein 1 （PD-1）/ programmed cell death 1 ligand（PD-L1）inhibitors in the treatment of non-small cell lung cancer related pharmacoeconomic studies in China. METHODS ：Retrieved from Embase ，PubMed，Medline，Cochrane Library ，CNKI，Wanfang database ，VIP and other Chinese and English database ，cost-utility studies about PD- 1/PD-L1 inhibitors in the treatment of non-small cell lung cancer published during Jan. 2016-Jan. 2021 were collected. The data of the included studies were extracted. After the quality of the included studies was evaluated by using the Consolidated Health Economic Evaluation Reporting Standards list ，the relevant data were summarized and compared from the aspects of model framework ，model parameters and uncertainty analysis. RESULTS & CONCLUSIONS：A total of 17 studies were finally included ，the overall quality of them was high but the differences in methodology were great. Markov model or partition survival model based on three states was adopted for 16 studies. The time horizon ranged from 5 years to lifetime ；the cycle length ranged from 1 week to 6 weeks. A total of 8 studies used the standard parameter distribution method for parameter fitting ，and 7 studies additionally adopted other parameters estimation methods as KM curves or spline models. Eleven studies performed the validation of model extrapolation. All studies considered the direct medical costs and reported the incremental cost-effectiveness ratio using quality-adjusted life years as the health outcome. Sixteen studies conducted the deterministic sensitivity analysis and probabilistic sensitivity analysis to improve the stability of the model. It is suggested that studies should keep the integrity of the report ； format，choose the appropriate positive comparators ，selectthe health economic model and construct reasonable assumptions according to the available data format ， use Cholesky decomposition to explore the uncertainty of the parameter fitting ， perform the validation of extrapolation combined with external data and use the appropriate indirect comparison in the absence of the head-to-head clinical trials to improve the quality of related pharmacoeconomic studies in China.

Correlation of adolescents internalizing problem behavior with genetic and environmental factors / 中国神经精神疾病杂志

Objective To explore the relationship of adolescents internalizing problem behavior with genetic and environmental factors. Methods The internalizing problem behavior of 74 twin pairs from Chongqing(aged from 12 to18 years) were investigated using The Youth Self-Report (YSR). The family adaptability and cohesion evaluationscale 2nd edition Chinese version (FACES Ⅱ-CV), Family Stresses Questionnaire (FSQ), the Parenting Styles and Dimensions Questionnaire (PSDQ), Stressful Life Event (SLE) and Simplified Coping Style Questionnaire (SCSQ ) were applied to assess their environment factors and coping style. The blood sample was collected to verify zygosity of twins. Structural equation modeling (SEM)was performed to evaluate the relationship of adolescents internalizing problem behavior with the additive genetic factors(A),shared environment factors(C)and individual specific environmental factors(E). Results The scores of PSDQ and FSQ FACES Ⅱ-CV SCSQ were no significantly different between homozygotic and dizygotic twins(P>0.05).There were significantly negative correlation between internalizing problem behavior and family cohesion (r=0.223, P=0.011).The scores of adolescent internalizing problem behavior were positively correlated with the scores of family stresses(r=0.232, P=0.008), the scores of Authoritarian-parenting-style(r=0.206, P=0.018), the scores of negative coping style (r=0.408, P=0.001);the scores of adolescents internalizing behavioral problems were not significantly correlated with the scores of the stress life events, and the scores of the parenting education level and occupation.The effects of A and E on adolescent internalizing problem behavior were 0.51(95%CI:0.27~0.69)and 0.49 (95% CI: 0.31~0.73) respectively. Conclusion Environmental factors and genetic factors contribute equally to adolescents internalizing problem behavior, which is affected by the authoritarian-parenting-style, family stresses, family cohesion and negative coping style.

A twin study of behavioral problems and relations to genetic and environmental factors in adolescents / 中国心理卫生杂志

Objective:To explore the relations of adolescents'behavioral problems to genetic and environmental factors.Methods:66 twin pairs aged 12 to 18 years in Chongqing were included in the study.The Youth Self-Report (YSR) was used to evaluate behavioral problems.The blood sample was collected to identify zygosity of twins.Genetic effects were evaluated by comparing the phenotypic correlationamong monozygotic twins(rMZ) and the phenotypic correlation among dizygotic twins(rDZ).Structural equation modeling (SEM) was performed to evaluate the relations of adolescents behavioral problems to the additive genetic factors (A),shared environment factors (C) and individual specific environmental factors (E).Results:MZ correlations of Social problems and Delinquency were less than DZ correlations(rMZ ＜ rDZ).It prompted that data was not suitable for genetic analysis.MZ correlations(rMZ) of any others (including social withdrawal,somatic complaints,anxiety/depression,thinking problem,attention problems,self-destructive/identity problem)were less than 2DZ correlations (2rDZ).It prompted to fit the ACE model.The optimal model was AE model.Among the contribution of the additive genetic factors (A) and individual specific environmental factors (E)to the total variance,the genetic factors ranged from 0.52 to 0.57 and individual specific environmental factors ranged from 0.43 to 0.48 in anxiety/depression and self-destructive/identity problem.For social withdrawal,somatic complaints,thinking problem and attention problems,the genetic factors ranged from 0.17 to 0.45and individual specific environmental factors ranged from 0.55 to 0.83.Conclusion:There is no obvious relationship between genetic effects and adolescent social problems or delinquency.Other behaviors problems (social withdrawal,somatic complaints,anxiety/depression,thinking problem,attention problem,self-destructive/identity problem)are correlated with additive genetic factors and individual specific environmental factors.Additive genetic factors have high-correlation with anxiety/depression and self-destructive/identity problem,and individual specific environmental factors have high-correlation with other factors.

A twin study on influential factors of adolescent depressive symptoms / 中国神经精神疾病杂志

Objective To explore the influence of genetic and environmental factors on adolescents depressive symptoms. Methods The depressive mood were investigated in 107 twin pairs from Chongqing (aged from 11 to 18 years old) using Beck Depression Inventory (BDI). The Parenting Styles and Dimensions Questionaire (PSDQ), Family Stresses Questionnaire (FSQ), Family Adaptability and Cohesion Scale 2nd Edition Chinese Version (FACES II-CV) and Stressful Life Event (SLE) were applied to assess their environment factors. The blood samples were collected to identify zygosity of twins. Structural equation model was performed to evaluate the effects of the additive genetic factors (A), shared envi?ronment factors (C) and individual specific environmental factors (E) on the adolescents depressive mood. Results The scores of depressive mood were negatively correlated with father’s education level (r=-0.15, P=0.03), mother’s educa?tion level (r=-0.17, P=0.01), scores of the authoritative-parenting-style (r=-0.18, P0.05). The effects of A and E on adolescents depressive symptoms were 0.37 (95%CI:0.14~0.57) and 0.63 (95%CI:0.43~0.86), respectively. Conclusion The authoritative-parenting-style and fami?ly adaptability are negatively correlated with depressive mood. Family stresses are positively correlated with depressive mood. Adolescents depressive mood is influenced by genetic factors and, to a greater extent, specific environmental factors.

Association of gender, age, education and polymorphism of DRD4 gene with cognitive functions in adults / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of cognitive functions with gender, age, education and polymorphism of dopamine receptor D4 (DRD4) gene in healthy adults.</p><p><b>METHODS</b>Four hundred and fifty-five healthy participants have completed 3 cognitive function tests including Tower of Hanoi (TOH), Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT). Peripheral blood samples were collected from all participants, and genomic DNA was extracted according to a standard phenol-chloroform procedure. Rs3758653 in the promoter region of the DRD4 gene was genotyped using Illumina GoldenGate genotyping assay.</p><p><b>RESULTS</b>Males have performed better than females in terms of TOH executive time and TOH total score, but did worse in TOH planning time. Most of the measured cognitive domains were affected by age and education. Cognitive ability has decreased along with increased age and decline of educational years. The polymorphism of rs3758653 has mainly correlated with the TOH executive time. Compared with A allele carriers, G allele carriers did worse in TOH executive time.</p><p><b>CONCLUSION</b>Gender, age, education and the rs3758653 polymorphism of the DRD4 gene play an important role in cognitive functions in healthy adults.</p>

Association study of LIS1 and TSNAX genes with bipolar disorder in Chinese Han population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of neural development-related genes LIS1and TSNAX with bipolar disorder in a Chinese Han population.</p><p><b>METHODS</b>Three hundred and eight five patients (including 188 males and 197 females) from Guangzhou Brain Hospital with bipolar disorder meeting the Diagnostic and Statistic Manual of Bipolar Disorder (BDI) (Fourth Edition) criteria and 475 healthy controls from the local community were recruited. Ten single nucleotide polymorphisms (SNPs) of the LIS1 and TSNAX genes were genotyped by GoldenGate genotyping assay on an Illumina Beadstation 500 machine. Association analyses of SNPs and haplotypes were performed with Plink 1.07 software.</p><p><b>RESULTS</b>Analysis of the total sample has failed to find any association of SNP or haplotype of the two genes with BDI (P> 0.05). When patients were divided into subgroups with or without psychotic symptom, no significant association of the two genes was found with psychotic BDI or non-psychotic BDI (P> 0.05). No significant association was found between any SNP and haplotype of two genes and female BDI or male BDI, nor were significant association found between age of onset and LIS1 and TSNAX gene polymorphisms.</p><p><b>CONCLUSION</b>Our results indicated that LIS1 and TSNAX genes are not associated with susceptibility to bipolar I disorder in Chinese Han population.</p>

Lack of association of COMT Val158Met polymorphism with attention and executive function in patients with schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the association of a functional polymorphism Val158Met of COMT gene and attention and executive function in first-episode treatment-naive patients with schizophrenia and healthy controls.</p><p><b>METHODS</b>Trail making test (TMT) and clinical performances were evaluated in 103 first-episode treatment-naive patients with schizophrenia and 99 healthy controls. Polymorphism of COMT Val158Met was analyzed using polymerase chain reaction-restriction fragment length polymorphism method. A general linear model was used to investigate the effect of genotype subgroups on the attention and executive function.</p><p><b>RESULTS</b>There was a significant difference between control subjects and patients with schizophrenia on the TMT-A and B. However, no significant difference among Val/Val, Val/Met and Met/Met on the TMT-A and B in control subjects and patients with schizophrenia was detected.</p><p><b>CONCLUSION</b>The association among COMT Met variant and trail making testing (attention and executive function) has been replicated. However, no association of COMT Met variant with disruption of dopaminergic influence on neurocognitive function was detected. This may be due to the heterogeneity of population.</p>

Regulation of PI3K-Akt-GSK3β signaling pathway in U251 cells by risperidone / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the effect of risperidone, an antipsychotic drug, on the Akt-GSK3β pathway and the role of PI3K in dopamine D2 receptor (DRD2) expression and Akt-GSK3β signal pathway.</p><p><b>METHODS</b>Human glioma cells (U251) were cultured in vitro. Cells without any treatment as control, Western blotting was used for measuring the expression of Akt (Thr308 and Ser473) and GSK3β (Ser9) protein phosphorylation by risperidone and LY294002 in U251 cell, and real-time PCR was used for detecting the expression of DRD2 mRNA.</p><p><b>RESULTS</b>Risperidone has significantly enhanced the expression of phosphorylated Akt and phosphorylated GSK3β (P< 0.05), but did not alter the mRNA expression of DRD2. LY294002 could reduce the phosphorylation of Akt and GSK3β (P< 0.01, P< 0.05), and also decrease the DRD2 mRNA (P<0 .05).</p><p><b>CONCLUSION</b>Risperidone can activate the Akt-GSK3β signaling pathway in the U251 cells, and PI3K is a common regulatory site in Akt-GSK3β signaling and D2 receptor gene expression.</p>

Effect of hereditary and environmental factors on the executive function of twin children / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the influence of genetic and environmental factors on the executive function of twin children.</p><p><b>METHODS</b>The executive function of 122 twin pairs from Chongqing (aged from 6 to 18 years) were investigated with the perseverative errors of the Wisconsin Card Sorting Test. Structural equation modeling was performed to evaluate the effects of the additive genetic factors (A), dominance genetic latent factors (D) and individual specific environmental factors (E) on the executive functions.</p><p><b>RESULTS</b>The effects of D and E on perseverative errors were 0. 77 (95%CI: 0.65-0.84) and 0.23 (95%CI: 0.16-0.35), respectively. The probability of perseverative errors showed a significant negative correlation with family functioning and with the total GHQ-12 scores of the fathers and mothers (r:-0.335, -0.335, and -0.219, respectively, P<0.01). Perseverative errors were not significantly correlated with the parenting styles and stress life events.</p><p><b>CONCLUSION</b>Perseverative errors are influenced by a common dominance genetic latent factor and individual specific environmental factors, but the role of environmental factors such as family functioning and parental health can not be ignored.</p>

A twin study of genetic effects on intelligence development of children and adolescents / 重庆医学

Objective Using twins methods to explore the influence of genetic and environmental factor on Intelligence develop-ment of children and adolescent twins .Methods It was 190 pair of twins aged 6 to 18 who lived in Chongqing were recruited ,DNA were extracted from buccal mucosa and venous blood samples to identify zygosity .The intelligence was investigated by using the Wechsler Intelligence Scale for Children(C-WISC) ,the intrapair correlation coefficients of twins were compared and calculate the genetic degrees .Results The total IQ of children aged 6 to 18 heritability were 0 .63 ,Verbal IQ were 0 .44 ,Performance IQ were 0 .57 .The total IQ heritability of children aged 10 to 14 and 15 to 18 years(0 .78 ,0 .79) were higher than that of those aged from 6 to 9 years(0 .018) .Conclusion This study suggested the intelligence of children aged 6 to 18 affected by genetic and environment , and the older ,the more influence of genetic on intelligence development .

Genetic and environmental influences on emotional and behavioral problems in children and adolescents / 中国神经精神疾病杂志

Objective To explore the influence of genetic and environmental factors on emotional and behavioral problems in children and adolescents using twins quantitative method. Methods One hundred fifty-six twins pairs, aged from 6 to 18, were included in the present study. The parental version of the strengths and difficulties questionnaire (SDQ)was used to evaluate their emotional and behavioral problems. The DNA test of twin zygosity was conducted using DNA extracted from buccal mucosa or venous blood samples. The influence of genetic and environmental factors on emo-tional and behavioral problems was analyzed using structural equation modeling(SEM). Results Shared environment and special environment had impact on emotional symptoms and their contribution to the total variance of emotional symp- tom was 0.42 and 0.58, respectively. Prosocial behavior was mainly affected by shared environment and the contribution of shared environment to the total variance of prosocial behavior was 0.89. Genetic factors had greater influence on hyperac-tivity/attention deficit and the contribution of genetic factors to the total variance was 0.62. Shared environment had more influence on conduct disorder and the contribution of shared environment to total variance was 0.56. Heredity, shared envi-ronment and special environment had impact on peer problems and their contribution to the total variance was 0.24, 0.33 and 0.43, respectively. Conclusion In child and adolescent period, emotional symptoms are only affected by environ-ment, while behavior problems are affected by the combination of heredity and environment. Different behavior problems are affected by different genetic and environmental factors.

A proton magnetic resonance spectroscopy imaging study on prefrontal lobe and hippocampus in male patients with first-episode mania / 中华行为医学与脑科学杂志

ObjectiveTo identify the metabolic alterations on prefrontal lobes and hippocampus in male patients with the first-episode mania using proton magnetic resonance spectroscopy(H-MRS).Method 18 male patients with the first-episode mania and 27 healthy subjects matched for age,gender,and years of education were included in the study.1 H-MRS was performed in two sides of the hippocampus and frontal lobes regions.The ratios of N-acetylaspartate (NAA),choline (Cho) to creatine (Cr) were measured.One-sample t test and paired-samples t test were used for statistic process.ResultsMale patients with the first-episode mania presented decreased NAA/Cr in left frontal lobe and hippocampus regions when compared to normal controls( left frontal lobe (1.68 ±0.19 vs 1.86 ± 0.19),hippocampus ( 1.32 ± 0.10 vs 1.43 ± 0.16 ),P ＜ 0.01 ),but there were no significant difference in NAA/Cr for right frontal lobe and hippocampus regions between groups ( all P ＞ 0.05 ).Two groups also showcd no significant difference for Cho/Cr in bilateral frontal lobe and hippocampus (P ＞ 0.05 ).Conclusion There is significant difference of manifestation of 1H-MRS between male patients with mania and normal controls,which reflects neuronal dysfunction in the prefrontal lobes and hippocampus.

A Prospective Twin Registry in Southwestern China: exploring the effects of genetic and environmental factors on cognitive and behavioral development and mental health well-being in children and adolescents / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>The goals, prospects and methods of the Prospective Twin Registry in Southwestern China (TRiSC) are described. The aim of this study is to measure children's behavioral development and psychopathology from phenotypic, genetic and environmental perspectives.</p><p><b>METHODS</b>The children's self-report, as well as parental and teachers' informant report were used to measure the children's behavior and psychopathology, and the latter was related to the children's general cognitive abilities, and to the parenting style. Other variables of interest such as children's temperament and parental health status were also used.</p><p><b>RESULTS</b>Nine thousand and three hundred thirty nine pairs of 0-16 years old twins have been registered, 324 pairs of them were monozygotic based on DNA samples as well as the detailed information on behavioral and cognitive aspects.Analysis has been performed for the influences of genetic and environmental factors on children's behavior and cognition.</p><p><b>CONCLUSION</b>School-based twins recruitment is a helpful method in child and adolescent twin study. TRiSC has been a valuable resource for research on the development of children's behavior and cognition.</p>

Association of the polymorphisms in NURR1 gene with Parkinson's disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association between the polymorphisms of [c.-2922(C)2-3 and IVS6+ 18insG] in the NURR1 gene and Parkinson's disease (PD) in a Han population from Sichuan province.</p><p><b>METHODS</b>PCR, allele-specific PCR (AS-PCR) and restriction fragment length polymorphism (RFLP) were used to determine the genotype of each subject.</p><p><b>RESULTS</b>The two polymorphic sites in 241 PD patients and 236 controls with matched age, gender and ethnicity were analyzed. In the IVS6+ 18insG site, the difference of genotype frequencies of 3G/3G, 3G/2G and 2G/2G was not statistically significant. However, the 3G/2G genotype frequency was significantly higher in the PD with age of onset being < 50 years than that in controls (chi (2)= 6.537, P= 0.011; OR= 1.913, 95%CI: 1.159-3.158). No significant differences were found in allele and genotype frequencies of the c.-2922(C)2-3 site in the promoter region between the PD and controls (P= 0.766).</p><p><b>CONCLUSION</b>This study suggested that the IVS6+ 18insG polymorphism may be associated with genetic susceptibility of PD with age of onset being < 50 years and the c.-2922(C)2-3 site in the promoter region may not be a risk factor for PD in authors' patient group.</p>

The A-204C Polymorphism in CYP7A1 Gene Affects Its Promoter Activity / 中国生物化学与分子生物学报

cholesterol 7α-hydroxylase gene ( CYP7A 1 ) plays a key role in the catabolism of cholesterol into bile acids. To investigate whether the A-204C polymorphism in CYP7A1 gene affects the gene expression,using luciferase as the reporter gene, four recombinants were constructed by inserting forward or reverse sequence with A or C allele at the polymorphism site into the promoter-less vector pGL3-basic. The constructs were then transfected into four cell lines and the luciferase activity of each expression vector was examined by dual luciferase reporter gene assay system. The results showed that activities of the forward sequence of both genotypes were higher than that of reverse sequence. Promoter activity of the recombinants with A allele was about one third lower than that with C allele. According to the analysis with TRANSFAC database, there may exist a Zic3 binding site when there is the C allele at -204. Our study indicates that the A-204 C polymorphism in CYP7A1 promoter region decreases its promoter activity and thus represses the gene expression, possibly due to the lack of a potential Zic3 binding site.

No evidence for genetic association between alpha-2 macroglobulin I1000V polymorphism and sporadic Alzheimer's disease in two independent Chinese populations / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>Alpha-2 macroglobulin (alpha2M) is a proteinase inhibitor found in association with senile plaques in Alzheimer's disease (AD). Also alpha2M has been implicated in several pathophysiological processes in AD. In view of the recent contradictory reports on the relationship between AD and a common polymorphism I1000V in A2M gene, the present authors studied a relatively large sample, determined the genotype of the I1000V polymorphism in A2M gene in sporadic AD patients and age-matched controls with normal cognition, and examined the possible association of the polymorphism with AD.</p><p><b>METHODS</b>Genotypes of A2M and apolipoprotein E (apoE) were detected by polymerase chain reaction combined with restriction fragment length polymorphism in 257 patients and 242 controls in Guangzhou, and 112 patients and 113 controls in Chengdu.</p><p><b>RESULTS</b>The 1000Val allele frequencies in the merged AD and control groups were 7.7% and 8.7%, respectively. The differences of allelic and genotypic frequencies between the patients and control subjects were not statistically significant, even after stratification by apoE epsilon4 status or by age-of-onset of the disease.</p><p><b>CONCLUSION</b>The results of this study revealed no association between the I1000V polymorphism of A2M and Chinese sporadic AD in Guangzhou and Chengdu.</p>

A linkage disequilibrium study of methylenetetrahydrofolate reductase C677T and schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the methylenetetrahy drofolate reductase (MTHFR) C677T missense mutation and schizophrenia by linkage disequilibrium study.</p><p><b>METHODS</b>Linkage disequilibrium analys is was conducted bet ween MTHFR C677T and schizophrenia in 115 affected-sib-pair (105) and trios (10) families by XDT and MAPMAKER/SIBS soft system. The analyses were performed in different diagnostic categories and combined with the age of onset as well.</p><p><b>RESULTS</b>No positive results were found in the analysis in all the family in all the four diagnostic categories. Significant P values, which were P<0.05, P<0.01 respectively, were observed in the families with the affected individual's onset age less than 25 years in all the four diagnostic categories.</p><p><b>CONCLUSION</b>The missense mutation of MTHFR C677T or other gene structure around this mutation may be one of the susceptibility gene of schizophrenia.</p>