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Backgrounds Cytochrome P450 (P450) 2E1 is one of the primary enzymes responsible for the metabolism of xenobiotics, such as drugs and environmental carcinogens. The genetic polymorphisms of the CYP2E1 gene in promoter and coding regions have been identified previously in the Han Chinese population from four different geographic areas of Mainland China. Methods To investigate whether genetic variants identified in the CYP2E1 coding region affect enzyme function, the enzymes of four single nucleotide polymorphism (SNP) variants in the coding region (novel c.1009C>T, causing p.Arg337X, where X represents the translational stop codon; c.227G>A, causing p.Arg76His; c.517G>A, yielding p.Gly173Ser; and c.1263C>T, presenting the highest allele frequency), two novel alleles (c.[227G>A;1263C>T] and c.[517G>A;1263C>T]), and the wild-type CYP2E1 were heterologously expressed in COS-7 cells and functionally characterized in terms of expression level and chlorzoxazone 6-hydroxylation activity. The impact of the CYP2E1 variant sequence on enzyme activity was predicted with three programs: Polyphen 2, PROVEAN and SIFT. Results The prematurely terminated p.Arg337X variant enzyme was undetectable by western blotting and inactive toward chlorzoxazone 6-hydroxylation. The c.1263C>T and c.[517G>A;1263C>T] variant enzymes exhibited properties similar to those of the wild-type CYP2E1. The CYP2E1 variants c.227G>A and c.[227G>A;1263C>T] displayed significantly reduced enzyme activity relative to that of the wild-type enzyme (decreased by 42.8% and 32.8%, respectively; P A transfectant was increased by 31% compared with the wild-type CYP2E1 enzyme (P T (p.Arg337X), c.227G>A (p.Arg76His), and c.517G>A (p.Gly173Ser), could influence the metabolism of CYP2E1 substrates, such as chlorzoxazone.

Human cytochrome P450 (CYP) enzymes, as membrane-bound hemoproteins, play important roles in the detoxification of drugs, cellular metabolism, and homeostasis. In humans, almost 80% of oxidative metabolism and approximately 50% of the overall elimination of common clinical drugs can be attributed to one or more of the various CYPs, from the CYP families 1–3. In addition to the basic metabolic effects for elimination, CYPs are also capable of affecting drug responses by influencing drug action, safety, bioavailability, and drug resistance through metabolism, in both metabolic organs and local sites of action. Structures of CYPs have recently provided new insights into both understanding the mechanisms of drug metabolism and exploiting CYPs as drug targets. Genetic polymorphisms and epigenetic changes in CYP genes and environmental factors may be responsible for interethnic and interindividual variations in the therapeutic efficacy of drugs. In this review, we summarize and highlight the structural knowledge about CYPs and the major CYPs in drug metabolism. Additionally, genetic and epigenetic factors, as well as several intrinsic and extrinsic factors that contribute to interindividual variation in drug response are also reviewed, to reveal the multifarious and important roles of CYP-mediated metabolism and elimination in drug therapy.

A number of recent genome-wide association (GWA) studies have identified several novel genetic determinants of plasma lipid and lipoprotein concentrations in European populations. However, it is still unclear whether these loci identified in Caucasian GWA studies also exert the same effect on lipid and lipoprotein concentrations in a Chinese population. We genotyped 10 single-nucleotide polymorphisms (SNPs) in nine loci in a Chinese Han population sample (n = 4,192) and assessed the associations of these SNPs with metabolic traits, using linear regression adjusted for age, gender, diabetes status, and body mass index. Three variants (rs12654264, P ∼ 1.7 × 10−6; rs3764261, P ∼ 7.1 × 10−7; and rs4420638, P ∼ 1.1 × 10−3) showed strong evidence for association with total cholesterol; four variants (rs780094, P ∼ 1.8 × 10−11; rs17145738, P ∼ 5.0 × 10−7; rs326, P ∼ 2.3 × 10−6; and rs439401, P ∼ 2.2 × 10−5) showed strong evidence for association with triglycerides, four variants (rs17145738, P ∼ 1.9 × 10−4; rs326, P ∼ 9.7 × 10−4; rs1800588, P ∼ 1.5 × 10−7; and rs3764261, P ∼ 4.3 × 10−14) showed strong evidence for association with HDL-cholesterol (HDL-C), two variants (rs12654264, P ∼ 2.3 × 10−5; and rs4420638, P ∼ 3.6 × 10−4) showed strong evidence for association with LDL-C, and four variants (rs326, P ∼ 2.8 × 10−3; rs1800588, P ∼ 6.1 × 10−4; rs3764261, P ∼ 2.0 × 10−3; and rs4420638, P ∼ 9.4 × 10−5) showed strong evidence for association with total cholesterol-HDL-C-related ratio. These SNPs generated strong combined effects on lipid traits and dyslipidemia. Our findings indicate that the variants that associated with metabolic traits in Europeans may also play a role in a Chinese Han population.

The centromere is responsible for the correct inheritance of eukaryotic chromosomes during cell division. Centromere protein B (CENP-B) and its 17 base pair binding site (CENP-B box), which appears at regular intervals in centromeric α-satellite DNA (α-satDNA), are important for the assembly of the centromere components. Therefore, it is conceivable that CENP-B box mutations may induce errors in cell division. However, the association between the deoxynucleotide alterations of the CENP-B box and the extra chromosome 21 (Chr21) present in patients with Down syndrome (DS) remains to be elucidated. The mutational spectrum of the α-satDNA, including 4 functional CENP-B boxes in Chr21 from 127 DS and 100 healthy children were analyzed by direct sequencing. The de novo occurrences of mutations within CENP-B boxes in patients with DS were excluded. The prevalence of 6 novel mutations (g.661delC, g.1035_1036insA, g.1076_1077insC, g.670T>G, g.1239A>T, g.1343T>C) and 3 single nucleotide polymorphisms (g.727C/T, g.863A/C, g.1264C/G) were not significantly different between DS and controls (P>0.05). However, g.525C/G (P=0.01), g.601T/C (P=0.00000002), g.1279A/G (P=0.002), g.1294C/T (P=0.0006) and g.1302 G/T (P=0.004) were significantly associated with the prevalence of DS (P<0.05). The results indicated that CENP-B boxes are highly conserved in DS patients and may not be responsible for Chr21 nondisjunction events. However, α-satDNA in Chr21 is variable and deoxynucleotide deletions, mutations and polymorphisms may act as potential molecular diagnostic markers of DS. [ABSTRACT FROM AUTHOR]

Study Question: Are genetic variations at the human solute carrier family 18 member A2 (SLC18A2) locus associated with the etiology of polycystic ovary syndrome (PCOS) and/or with follicle stimulating hormone (FSH) levels and insulin secretion in PCOS?Summary Answer: We found two common genetic variants in the 3'-untranslated region of SLC18A2 (rs363282 and rs363238) that are associated with serum FSH concentration in the PCOS group.What Is Known Already: SLC18A2 is a vesicular monoamine transporter that is essential in dopamine regulation. Dopamine can negatively regulate FSH and insulin secretion through the D2 receptor.Study Design, Size, Duration: This study was a cross-sectional examination in women with PCOS (n = 319) and controls (n = 220) from China.Participants/materials, Setting, Methods: The PCOS patients were diagnosed based on the criteria of the Androgen Excess Society, including clinical and/or biochemical signs of hyperandrogenemia plus oligoamenorrhea or polycystic ovaries. Controls had regular menstrual cycles and no hyperandrogenism or other endocrine disorders related to PCOS. Tag single nucleotide polymorphisms (SNPs) were selected based on resequencing data in 48 PCOS patients and linkage disequilibrium analysis. Allele frequencies for variants (rs363282 and rs363238) were examined in PCOS cases and controls along with their relationship to quantitative traits. The samples were further divided into two subgroups for association analysis: AA + AG group and GG group (rs363282), CC + AC group and AA group (rs363238). The functional effects of SLC18A2 variants were measured by luciferase assay. The gene expression of SLC18A2 was compared with the NCBI's Gene Expression Omnibus datasets.Main Results and the Role Of Chance: Two common genetic variants in the 3'-untranslated region (rs363282 and rs363238) are associated with serum FSH in the PCOS group (P= 0.005 and P= 0.001, respectively), while no associations were found in controls. Functional studies showed that minor alleles of the two variants (rs363282-G and rs363238-A) had significantly lower luciferase activities than rs363282-A (P= 0.009) and rs363238-C (P = 0.009).Limitations, Reasons For Caution: Results were not validated in another independent cohort, though we provided functional evidence of the two SNPs. Because of limited condition, more specific parameters, including ovarian follicle count and anti-Müllerian hormone were not included and relationship between SLC18A2 and these parameters cannot be evaluated.Wider Implications Of the Findings: We found a novel association between two genetic variants in SLC18A2 and FSH levels in PCOS patients. These findings might indicate a novel regulatory mechanism in follicular development and maturation in PCOS.Study Funding/competing Interests: This work was supported by the National Natural Science Foundation of China (grant numbers 81571501 and 81270747), National Basic Research Program of China (grant number 2015CB943300). No competing interests declared. [ABSTRACT FROM AUTHOR]

Objective: Genetic variabilities within the serotoninergic system may predict response or remission to antidepressant drugs. Several serotonin receptor (5-HTR) gene polymorphisms have been associated with susceptibility to psychiatric diseases. In this study, we analyzed the correlation between 5-HTR1A and 5-HTR2A polymorphisms and response or remission to selective serotonin reuptake inhibitors (SSRIs) drugs. Methods: Two hundred and ninety patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder were involved in this study. SSRIs (fluoxetine, paroxetine, citalopram, or sertraline) were selected randomly for treatment. The Hamilton Rating Scale for Depression was used to evaluate the antidepressant effect. To assess 5-HTR gene variabilities, two single-nucleotide polymorphisms in 5-HTR1A (rs1364043 and rs10042486) and three in 5-HTR2A (rs6311, rs6313, and rs17289304) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using the Sequenom MassARRAY Analyzer 4 system. Results: There were 220 responders and 70 nonresponders (120 remissioners and 170 nonremissioners) after 6 weeks of treatment. We found no association between any of the five 5-HTR1A and 5-HTR2A gene polymorphisms and antidepressant drug response or remission (P>0.05). It is worth mentioning that TT genotype frequency of rs10042486 was significantly different from the CT genotype frequency between responders and nonresponders, although the significance was not maintained after correcting for multiple testing. Conclusion: Thus, 5-HTR1A and 5-HTR2A gene polymorphisms may not play an important role in antidepressant drug response or remission. [ABSTRACT FROM AUTHOR]

Background: Psychiatric disorders such as schizophrenia and major depressive disorder (MDD) are likely to be caused by multiple susceptibility genes, each with small effects in increasing the risk of illness. Identifying DNA variants associated with schizophrenia and MDD is a crucial step in understanding the pathophysiology of these disorders.Aims: To investigate whether the SP4 gene plays a significant role in schizophrenia or MDD in the Han Chinese population.Method: We focused on nine single nucleotide polymorphisms (SNPs) harbouring the SP4 gene and carried out case-control studies in 1235 patients with schizophrenia, 1045 patients with MDD and 1235 healthy controls recruited from the Han Chinese population.Results: We found that rs40245 was significantly associated with schizophrenia in both allele and genotype distributions (Pallele = 0.0005, Pallele = 0.004 after Bonferroni correction; Pgenotype = 0.0023, Pgenotype = 0.0184 after Bonferroni correction). The rs6461563 SNP was significantly associated with schizophrenia in the allele distributions (Pallele = 0.0033, Pallele = 0.0264 after Bonferroni correction).Conclusions: Our results suggest that common risk factors in the SP4 gene are associated with schizophrenia, although not with MDD, in the Han Chinese population. [ABSTRACT FROM AUTHOR]

Variability in activity of CYP2C9, which is involved in the metabolism of approximately 15%of current therapeutic drugs, is an important contributor to interindividual differences in drug response. To evaluate the functional alternations of CYP2C9*2, CYP2C9*3, CYP2C9*8, CYP2C9*11 and CYP2C9*31, identified in our previous study in Chinese Han population, allelic variants as well as the wild-type CYP2C9 were transiently expressed in COS-7 cells. Kinetic parameters (Km, Vmax, and Clint) for S-warfarin 7- hydroxylation by these recombinant CYP2C9s were determined. Relative to CYP2C9.1, recombinant CYP2C9.3 and CYP2C9.11 exhibited significantly higher Km values, and all allelic variants showed significantly decreased Vmax and Clint values. Among all allelic variants, catalytic activity of CYP2C9.3 and CYP2C9.11 reduced the most (8.2% and 9.8% of Clint ratio, respectively; P < 0.001). These findings should be useful for < predicting the phenotype profiles of CYP2C9 in Chinese Han population, comparing the functional results of these alleles accurately, and finally optimizing pharmacotherapy of drug treatment. [ABSTRACT FROM AUTHOR]

Background: A large schizophrenia genome-wide association study (GWAS) and a subsequent extensive replication study of individuals of European ancestry identified eight new loci with genome-wide significance and suggested that the MIR137-mediated pathway plays a role in the predisposition for schizophrenia.Aims: To validate the above findings in a Han Chinese population.Method: We analysed the single nucleotide polymorphisms (SNPs) in the newly identified schizophrenia candidate loci and predicted MIR137 target genes based on our published Han Chinese populations (BIOX) GWAS data. We then analysed 18 SNPs from the candidate regions in an independent cohort that consisted of 3585 patients with schizophrenia and 5496 controls of Han Chinese ancestry.Results: We replicated the associations of five markers (P<0.05), including three that were located in the predicted MIR137 target genes. Two loci (ITIH3/4: rs2239547, P = 1.17 × 10(-10) and CALN1: rs2944829, P = 9.97 × 10(-9)) exhibited genome-wide significance in the Han Chinese population.Conclusions: The ITIH3/4 locus has been reported to be of genome-wide significance in the European population. The successful replication of this finding in a different ethnic group provides stronger evidence for the association between schizophrenia and ITIH3/4. We detected the first genome-wide significant association of schizophrenia with CALN1, which is a predicted target of MIR137, and thus provide new evidence for the associations between MIR137 targets and schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Genetic factors have been studied extensively for their role in the pathogenesis of primary open angle glaucoma (POAG). This study was conducted to investigate whether manganese superoxide dismutase ( SOD2) variants play a significant role in POAG in a Chinese population. Methods: This study included of 416 unrelated POAG patients and 997 unrelated control subjects. Four SOD2 tag single nucleotide polymorphisms (SNPs), including rs6917589 rs2842980, rs5746136 and rs4880, were genotyped by dye terminator-based SNaPshot method. The genotype and allele frequencies were evaluated using the χ2 tests. Results: Allelic association analysis showed that there were suggestive differences in the allelic distributions between POAG cases and controls for SNPs rs6917589 and rs5746136 ( p = 0.0.046 and p = 0.032, respectively), but no statistically significant association was detected between the two SNPs and POAG after Bonferroni correction ( p > 0.0125). The allele and genotype frequency in SNPs rs2842980 and rs4880 showed no statistically significant difference between POAG cases and controls ( p = 0.128 and p = 0.867, respectively). SNP rs5746136 had a significant association with POAG in the recessive model ( p = 0.003155). Haplotype ATGT generated from the four SNPs showed a trend of association with POAG ( p = 0.0098). Conclusion: Our results showed a trend of association with POAG, suggesting that SOD2 may play a significant role in the development of POAG in the Chinese population. Further work with a larger sample size and functional study is needed to confirm the importance of the SOD2 gene in the pathogenesis of glaucoma. [ABSTRACT FROM AUTHOR]

Background: Kashin-Beck disease is a kind of degenerative osteoarthropathy. Genetic factors may play an important role in the pathogenesis of KBD. Objective: To investigate the association of the selenoprotein genes GPX1 (rs1050450, rs1800668, and rs3811699), TrxR2 (rs5748469), and DIO2 (rs225014) with Kashin-Beck disease (KBD) in a Tibetan population and to investigate the association of these SNPs with the serum iodine/selenium concentration in the Tibetan population. Design: Five SNPs including rs1050450, rs1800668, and rs3811699 in the GPX1 gene, rs5748469 in the TrxR2 gene, and rs225014 in the DIO2 gene were analyzed in Tibetan KBD patients and controls using the SNaPshot method. P trend values of the SNPs were calculated using an additive model. Results: None of the five SNPs in the three genes showed a significant association with KBD. Haplotypes TCC, TTC and TTT of rs1050450, rs1800668 and rs3811699 in GPX1 showed a significant association with KBD and controls with P value of 0.0421, 5.0E-4 and 0.0066, respectively. The GPX1 gene (rs1050450) showed a potential significant association with the iodine concentration in the Tibetan study population (P = 0.02726). However, no such association was detected with the selenium concentration (P = 0.2849). Conclusion(s): In this study, we showed that single SNPs in the genes GPX1 (rs1050450, rs1800668 and rs3811699), TrxR2 (rs5748469), and DIO2 (rs225014) may not be significantly associated with KBD in a Tibetan population. However, haplotype analysis of SNPs rs1050450, rs1800668 and rs3811699 in GPX1 gene showed a significant association with KBD. The results suggested that GPX1 gene play a protective role in the susceptivity of KBD in Tibetans. Furthermore, the GPX1 gene (rs1050450) may be significantly associated with the serum iodine concentration in Tibetans. [ABSTRACT FROM AUTHOR]

CYP2E1 promoter polymorphisms can lead to significant interindividual differences in expression of CYP2E1. Using a database of CYP2E1 gene polymorphisms established in 2010, our study aimed to functionally characterize the single nucleotide polymorphisms (SNPs) of the promoter region and corresponding haplotypes in the Chinese Han population. Six novel SNPs and seven haplotypes with a frequency equal to or greater than 0.01 were constructed on a luciferase reporter system on the basis of site-directed mutagenesis. Dual luciferase reporter systems were used to analyze regulatory activity. The constructs including single novel SNP mutations exhibited insignificant change in luciferase activity, whereas, the activity produced by Haplo1(GTTGCTATAT), Haplo2 (CTTGCTATAT) and Haplo7 (GAGCTCACAT), containing a -333T>A polymorphism was significantly greater than for the wild type in Hep G2 cells (p<0.05), being 1.5-, 2.0- and 1.4- times greater respectively. These findings suggest the possibility of significant clinical prediction of adverse drug reaction and the facilitation of personalized medicine. [ABSTRACT FROM AUTHOR]

Background: CYP2E1 is a member of the cytochrome P450 superfamily, which is involved in the metabolism and activation of both endobiotics and xenobiotics. The genetic polymorphisms of CYP2E1 gene (Chromosome 10q26.3, Accession Number NC_000010.10) are reported to be related to the development of several mental diseases and to be involved in the clinical efficacy of some psychiatric medications. We investigated the possible association of CYP2E1 polymorphisms with susceptibility to schizophrenia in the Chinese Han Population as well as the relationship with response to risperidone in schizophrenia patients. Methods: In a case-control study, we identified 11 polymorphisms in the 5' flanking region of CYP2E1 in 228 schizophrenia patients and 384 healthy controls of Chinese Han origin. From among the cases, we chose 130 patients who had undergone 8 weeks of risperidone monotherapy to examine the relationship between their response to risperidone and CYP2E1 polymorphisms. Clinical efficacy was assessed using the Brief Psychiatric Rating Scale (BPRS). Results: Statistically significant differences in allele or genotype frequencies were found between cases and controls at rs8192766 (genotype p = 0.0048, permutation p = 0.0483) and rs2070673 (allele: p = 0.0018, permutation p = 0.0199, OR = 1.4528 95%CI = 1.1487-1.8374; genotype: p = 0.0020, permutation p = 0.0225). In addition, a GTCAC haplotype containing 5 SNPs (rs3813867, rs2031920, rs2031921, rs3813870 and rs2031922) was observed to be significantly associated with schizophrenia (p = 7.47E-12, permutation p<0.0001). However, no association was found between CYP2E1 polymorphisms/haplotypes and risperidone response. Conclusions: Our results suggest that CYP2E1 may be a potential risk gene for schizophrenia in the Chinese Han population. However, polymorphisms of the CYP2E1 gene may not contribute significantly to individual differences in the therapeutic efficacy of risperidone. Further studies in larger groups are warranted to confirm our results. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses a research regarding the relationship between vascular dementia (VaD) and Alzheimer's disease in Chinese population.

Introduction: Previous case-control studies have suggested that the endothelial nitric oxide synthase (eNOS) gene polymorphisms (G894T, 4b/a, T-786C) are associated with coronary artery disease (CAD). However, other studies do not confirm these relationships. The objective was to assess these relationships using meta-analysis. Methods: Databases, including Pubmed and Embase, were searched to access the relevant genetic association studies up to July 2009. Results: The meta-analysis included 56 studies, consisting of 23 studies for G894T, 19 for 4b/a and 14 for T-786C. For the allelic analysis of the G894T variant, all studies showed a positively significant association (OR = 0.83, p = 0.004). For the genotypic analysis, the combined studies of the T allele showed significance (OR = 1.57, p = 0.003). For the allelic analysis of the T-786C variant, all studies showed an obviously significant association (OR = 0.79, p = 0.0007), reflected in both non-Asian and Asian studies. For the genotype analysis, combined studies of the C allele showed significance (OR = 0.72, p = 0.0001). Moreover, non-Asian studies showed significant results. For the analysis of the 4b/a variant, none of the studies showed significant results. No publication bias was found in the meta-analysis. Conclusion: The synthesis of available evidence supports the fact that eNOS G894T andT-786C are associated with CAD. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A number of association studies have investigated the role of the nitric oxide synthase 3 (NOS3) gene in the development of diabetic nephropathy (DN). However, results have been inconclusive, largely because the studies have focused on a variety of different polymorphisms and generate inconsistent results. We performed a meta-analysis of 28 association studies focusing on three polymorphisms in the NOS3 gene (G894T (Glu289Asp), 4b/a, and T-786C) and the risk of DN published before July 2009, covering a total of 10,364 subjects. Although significant heterogeneity was initially found in the analysis of G894T, it did not remain when analysis was done by ethnic subgroups. 894T was negatively associated with DN in Caucasian populations of European origin (OR = 0.896, 0.817–0.983, 95% CI), but was positively associated with DN in East Asian (OR = 2.02, 1.20–3.42, 95% CI) and other populations. Association of the 4b/a variant was observed when studies involving microalbuminuria were excluded (OR = 1.19, 1.02–1.39, 95% CI). The T-786C variant showed an overall weak association (OR = 1.16, 1.01–1.34, 95% CI) with little heterogeneity. In summary, our meta-analysis of the effect of NOS3 gene polymorphisms on the risk of DN supports the involvement of the NOS3 gene in the pathogenesis of DN. [ABSTRACT FROM AUTHOR]

Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes. [ABSTRACT FROM AUTHOR]

Background: CYP2E1 encodes a member of the cytochrome P450 superfamily of enzymes which play a central role in activating and detoxifying many carcinogens and endogenous compounds thought to be involved in the development of cancer. The PstI/RsaI and DraI polymorphism are two of the most commonly studied polymorphisms of the gene for their association with risk of head and neck cancer, but the results are conflicting. Methods: We performed a meta-analysis using 21 eligible case-control studies with a total of 4,951 patients and 6,071 controls to summarize the data on the association between the CYP2E1 PstI/RsaI and DraI polymorphism and head and neck cancer risk, especially by interacting with smoking or alcohol. Results: Compared with the wild genotype, the OR was 1.96 (95% CI: 1.33-2.90) for PstI/RsaI and 1.56 (95% CI: 1.06-2.27) for DraI polymorphism respectively. When stratified according to ethnicity, the OR increased in the Asians for both polymorphisms (OR = 2.04, 95% CI: 1.32-3.15 for PstI/RsaI; OR = 2.04, 95% CI: 1.27-3.29 for DraI), suggesting that the risk is more pronounced in Asians. Conclusion: Our meta-analysis suggests that individuals with the homozygote genotypes of PstI/RsaI or DraI polymorphism might be associated with an increased risk of head and neck cancer, especially in Asians. [ABSTRACT FROM AUTHOR]

Background: Genetic factors related to the regulation of apoptosis in schizophrenia patients may be involved in a reduced vulnerability to cancer. XRCC4 is one of the potential candidate genes associated with schizophrenia which might induce colorectal cancer resistance. Methods: To examine the genetic association between colorectal cancer and schizophrenia, we analyzed five SNPs (rs6452526, rs2662238, rs963248, rs35268, rs2386275) covering ~205.7 kb in the region of XRCC4. Results: We observed that two of the five genetic polymorphisms showed statistically significant differences between 312 colorectal cancer subjects without schizophrenia and 270 schizophrenia subjects (rs6452536, p = 0.004, OR 0.61, 95% CI 0.44-0.86; rs35268, p = 0.028, OR 1.54, 95% CI 1.05-2.26). Moreover, the haplotype which combined all five markers was the most significant, giving a global p = 0.0005. Conclusions: Our data firstly indicate that XRCC4 may be a potential protective gene towards schizophrenia, conferring reduced susceptibility to colorectal cancer in the Han Chinese population. [ABSTRACT FROM AUTHOR]

Estrogen was considered to be an important protective factor for cardiovascular diseases in women. Genetic association studies suggested that variations of ESR1and ESR2 genes might have a potential role in lipid profile. Our study aimed to investigate the association of single-nucleotide polymorphisms (SNPs) of ESR1 and ESR2 with hyperlipidemia in Chinese Han postmenopausal women. A total of 443 postmenopausal women aged between 55 and 71 years were recruited from Shanghai, China for a case–control study (154 women with hyperlipidemia and 289 controls). We measured plasma estradiol concentration, glucose and lipid profile levels, evaluated their lifestyle and sequenced four SNPs, namely PvuII (rs2234693) and XbaI (rs9340799) of ESR1 and 1082A>G (rs1256049) and 1730A>G (rs4986938) of ESR2. PvuII (rs2234693) and XbaI (rs9340799) showed significantly different distributions between cases and controls (P=0.002 and P=0.023, respectively). In addition, haplotypes constructed from PvuII–XbaI were also associated with hyperlipidemia (global P=0.012). Haplotypes T–A (P=0.005, odds ratio (OR) 1.52, 95% confidence interval (95% CI): 1.13–2.05) and C–G (P=0.010, OR 0.62, 95% CI: 0.43–0.89) had susceptible and protective effects, respectively. 1082A>G (rs1256049) and 1730A>G (rs4986938) showed no statistical association with hyperlipidemia. In conclusion, our results suggested that ESR1 might have a potential role in hyperlipidemia risk, independent of age, estradiol level, body mass index and lifestyle in Chinese Han postmenopausal women. [ABSTRACT FROM AUTHOR]

The COMT gene is considered as one of the prominent candidate genes for susceptibility to BP, and most studies focused a functional polymorphism in the gene: the Val/Met polymorphism (rs4680). However, results from these studies are sometimes contradictory, due to small sample size or heterogeneity. In this study, we first investigate the possible association between the Val/Met polymorphism in COMT and bipolar disorder in the Han population, which has never been done before. Then a systematic meta-analysis was conducted to determine if the low-activity allele (Met) increases the risk of BP in different ethnic groups. A total of 478 BP patients and 469 healthy subjects were recruited in our case/control study. MIX software package was employed to perform the meta-analysis on 19 studies after careful search and selection. We observed statistically-significant differences in allele ( p = 0.00060) and genotype ( p = 0.00203) frequencies between patients and controls in our samples. The meta-analysis also provided a significant pooled OR for association of the Met allele in rs4680 with BP in the total population ( p = 0.0223) and in the Asian population ( p = 0.0232). Although a significant pooled OR was also found for the Caucasian population ( p = 0.0409) after one of the studies as discussed below was removed, the role for Val/Met polymorphism in BP in Caucasian ethnicity was not yet to be confirmed. In conclusion, the low-activity allele (Met) of rs4680 in COMT gene possibly confers risk for bipolar disorder in the Han population, while it needs further evidence for concluding its association with BP in the Caucasian population. [ABSTRACT FROM AUTHOR]

Aims: To date, there have been relatively few studies on the UGT1A6 gene in the Chinese population. The present study was designed to determine the allele frequencies and haplotypes of this gene in the population and predict the candidate functional mutations. Materials & methods: We carried out the first systematic screening of polymorphisms of the gene in an SNP analysis involving 1074 Chinese subjects from three ethnic groups, namely Han, Dong and She, using direct sequencing. We identified the putative substrate binding pocket using a homology-modeled structure and produced a practical model for predicting the function of polymorphisms in UGT1A6. Results: A total of six SNPs and 10 mutations were detected including nine known and seven novel ones. The novel mutations were 73G>A (V25I), 89T>G (L30R), 222A>C, 657C>A, 773A>T (D258V), 1040A>G (N347S) and 1467C>T. In addition, we detected, for the first time in the Chinese population, SNPs 105C>T, 627G>T as well as mutations 308C>A (S103X), IVS2+15T>C and 1088C>T (P363L). Strong linkage disequilibrium was observed among 19T>G, 315A>G, 541A>G and 552A>C. There were seven haplotypes whose frequencies were more than 0.01 in one or more of the three ethnic groups. P363L in the C-terminal domain might weaken the binding of cofactor UDPGA to the domain and induce a poor metabolism genotype of UGT1A6. Conclusion: Our study suggests that genetic polymorphisms in UGT1A6 may contribute to interindividual and intra-ethnic differences. The results should prove helpful in the development of pharmacogenomics in China. [ABSTRACT FROM AUTHOR]

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Background: 2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNP), one of the promising candidate genes for schizophrenia, plays a key part in the oligodendrocyte function and in myelination. The present study aims to investigate the relationship between CNP and schizophrenia in the Chinese population and the effect of different factors on the expression level of CNP in schizophrenia. Methods: Five CNP single nucleotide polymorphisms (SNPs) were investigated in a Chinese Han schizophrenia case-control sample set (n = 180) using direct sequencing. The results were included in the following meta-analysis. Quantitative real-time polymerase chain reaction (PCR) was conducted to examine CNP expression levels in peripheral blood lymphocytes. Results: Factors including gender, genotype, sub-diagnosis and antipsychotics-treatment were found not to contribute to the expression regulation of the CNP gene in schizophrenia. Our meta-analysis produced similar negative results. Conclusion: The results suggest that the CNP gene may not be involved in the etiology and pathology of schizophrenia in the Chinese population. [ABSTRACT FROM AUTHOR]

Aims: Although many studies have been performed on CYP2C19, most of them have mainly examined the effects of the defective alleles CYP2C19*2 and CYP2C19*3. A comprehensive search for genetic polymorphisms of the CYP2C19 gene in the Chinese Han population has rarely been conducted. The present study was designed to determine the genetic basis of CYP2C19 polymorphisms. Materials & Methods: We investigated the 5'- regulatory region, all the exons and their surrounding introns of the CYP2C19 gene in 400 unrelated healthy Chinese Han volunteers from four different geographical locations, namely Shanghai, Shantou, Shenyang and Xi'an, with a sample of 100 subjects in each population, using direct sequencing. Results: A total of 14 different CYP2C19 polymorphisms, including one novel variant (-2306G>A) in the enhancer region and a novel nonsynonymous one (905C>G, T302R) were identified. In addition, CYP2C19*1, *2, *3, *15 and *17 alleles showed frequencies of 69.7%, 24.7%, 3.3%, 1.2% and 1.2%, respectively, and CYP2C19*15 was the first detected in an Asian population. The frequencies of the prevalent defective alleles CYP2C19*2 and CYP2C19*3 in Chinese Han populations are similar to those in other Asians, and much higher than those reported in American European and other Caucasian populations. Haplotype analysis demonstrated CATCGG was the dominating haplotype with a frequency of 38.6% in the Chinese Han population. Furthermore, homology modeling analysis for CYP2C19 indicates that Thr302Arg could cause the displacement of heme. Conclusion: This is the first study that systematically screened the polymorphisms of the whole CYP2C19 gene in a large Chinese Han population. The results suggest that a few low frequent variants show significant differences among the four populations, while the prevalent polymorphisms show no differences. Therefore, our database provides important information on CYP2C19 polymorphisms in the Chinese population, and could be helpful for future personalized medicine studies in Asian populations generally. [ABSTRACT FROM AUTHOR]

Previous observations of the anatomical distribution and pharmacological profile of the dopamine D3 receptor (DRD3) have indicated its potential role in antipsychotic drug action. Risperidone, an effective first-line atypical antipsychotic agent, exhibits a relatively high affinity for this receptor. Recent studies have reported an association of the Ser9Gly polymorphism in the DRD3 gene with therapeutic response to risperidone, but the results were inconsistent. We therefore postulated that the Ser9Gly polymorphism might be in linkage disequilibrium with an undetected variant that exerts a direct influence on risperidone efficacy. The present study genotyped eight single nucleotide polymorphisms (SNPs) distributed throughout the DRD3 gene and examined five of these for association with treatment outcome, following an 8-week period of risperidone monotherapy in 130 schizophrenic patients from mainland China. Clinical symptoms were assessed before and after the treatment period, using the Brief Psychiatry Rating Scale (BPRS). The confounding effects of non-genetic factors were estimated and the baseline symptom score was included as a covariate for adjustment. Neither was any association observed between the five polymorphisms and improvement in total BPRS scores nor was any combined effect of these variants detected in the haplotype analysis. The current results indicate that genetic variations within the DRD3 gene may not contribute significantly to interindividual differences in the therapeutic efficacy of risperidone.Neuropsychopharmacology (2008) 33, 305–311; doi:10.1038/sj.npp.1301418; published online 11 April 2007 [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) in tumor necrosis factor alpha ( TNFα) promoter with rheumatoid arthritis (RA) in Chinese Han population. Six SNPs at positions −238, −244, −308, −376, −857, −863 within TNFα promoter were genotyped in 367 unrelated RA patients and 271 healthy controls, using direct DNA sequencing method. Allelic, genotypic, and haplotypic associations of these SNPs with RA were examined. The frequencies of TNFα −308A allele and the haplotype GACC (in order of −238, −308, −857, −863) were significantly lower in RA patients when compared with healthy controls ( P = 0.0046, P = 0.0045, respectively) but TNFα −308 polymorphism was not related to the clinical manifestations of RA patients. These results implied that TNFα gene itself or a gene in linkage disequilibrium with it might be associated with RA in Han population of Eastern China. [ABSTRACT FROM AUTHOR]

Risperidone is a widely used atypical antipsychotic medication and there is currently considerable interest in individual differences in patient response to it. In this study, we investigated the pharmacogenetic correlates of SLC6A3 and response to risperidone treatment in 130 Chinese schizophrenia patients. We selected six polymorphisms, including two SNPs in the 5'-regulatory regions, two SNPs in intron 1, one SNP and a variable number tandem repeat in the 3'-flanking region of SLC6A3 for this study and analyzed the differences in the reduction of Positive and Negative Syndrome Scale (PANSS) scores among the subgroups with different genotypes and diplotypes after 8 weeks of risperidone treatment. The confounding effects of nongenetic factors were estimated and the baseline symptom score was included as a covariate for adjustment. We found no significant differences in response to treatment in terms of PANSS or subscores improvements among the subgroups according to different genotypes and diplotypes. In addition, we have found no significant differences between different diplotypic groups in the plasma levels of risperidone and 9-hydroxyrisperidone. Further studies on larger groups and on the effects of longer-term risperidone treatment are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Antipsychotic drugs exert both therapeutic and adverse effects through dopamine D2 receptor (DRD2) antagonism. Genetic variants of this receptor may be responsible for individual variations in neuroleptic response and may therefore be useful in predicting response. In this study we evaluated the role of six polymorphisms of the DRD2 gene in 125 risperidone-treated Chinese schizophrenia patients following the hypothesis that variation in the DRD2 gene could affect drug response. Response was categorized as a change of >40% on the Brief Psychiatric Rating Scale (BPRS). Our results show that genotyping A-241G may help to predict the efficacy of risperidone treatment on the basis that patients with the A allele showed greater improvement than those with the C allele on the overall BPRS (χ² = 7.19, p = 0.007, p = 0.031 after correction by the program SNPSpD), while other polymorphisms, including -141C Ins/Del, TaqIB, rs1076562, T939C and TaqlA, did not show any association with the response to risperidone. These data suggest that the DRD2 A-241G polymorphism or, alternatively, another genetic variation that is in linkage disequilibrium, may influence response to risperidone in schizophrenia patients. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequencies and haplotypes of the cytochrome P450 (CYP)3A7 gene in three Chinese ethnic groups, namely, Han, She and Dong. Methods: SNP analyses of the CYP3A7 gene were carried out on three groups of healthy Chinese subjects consisting of 539 Han, 264 She and 273 Dong subjects, using direct sequencing. Linkage disequilibrium, haplotype inference and Hardy-Weinberg equilibrium were also determined for these samples. Results: Significant differences were observed in the distribution of SNP rs2257401 (CYP3A7*2), SNP 1227 T>C (Novel), SNP rs4646468 and SNP rs10211 between the Han, She and Dong groups. Conclusion: Some allele and haplotype frequencies show variation among groups, highlighting the need to analyze clinically relevant SNPs and haplotypes in a variety of different racial groups within the Chinese population as well as in other ethnic groups. These results suggest that genetic polymorphisms in the CYP3A7 gene in the Han, She and Dong populations may contribute to interindividual as well as intra-ethnic differences in response to the clearance of CYP3A7 substrates. [ABSTRACT FROM AUTHOR]

P-glycoprotein, a product of the ATP-binding cassette B1 (ABCB1) gene, plays an important role in absorption and distribution of drugs. The brain entry of risperidone and 9-OH-risperidone is greatly limited by P-glycoprotein, which implies that the functional polymorphisms of ABCB1 in humans may be a factor contributing to the variability in response to risperidone. The present study was therefore designed to examine whether polymorphisms of the ABCB1 gene are related to therapeutic response. For this purpose, 130 Chinese schizophrenia patients undergoing risperidone treatment were recruited. Plasma drug concentrations were monitored and clinical symptoms were evaluated using the Brief Psychiatric Rating Scale (BPRS) before and 8 weeks after the treatment. Association tests between genotypes and percentage improvement in total BPRS scores were performed using analyses of variance. Our results show that genotyping C1236T may help to predict the efficacy of risperidone treatment on the basis that patients with the TT genotype showed greater improvement than those with other genotypes on the overall BPRS (F = 3.967, p = 0.021), while other polymorphisms, including rs13233308, G2677T/A and C3435T polymorphism, did not show any association with the response to risperidone. These results showed suggestive evidence that genetic variation in the ABCB1 gene may influence the individual response to risperidone. [ABSTRACT FROM AUTHOR]

Objectives: Cytochrome P450 3A4 (CYP3A4) is a major CYP enzyme in the liver and intestine. It is involved in the metabolism of over 50% of all drugs currently in use. The present study was designed to determine the genetic basis of CYP3A4 variability. Methods: Single nucleotide polymorphism (SNP) analysis of the CYP3A4 gene was performed on 60 healthy Chinese subjects consisting of 20 Han, 30 She and ten Dong subjects, using direct sequencing. Linkage disequilibrium, haplotype inference and Hardy-Weinberg equilibrium were also determined for these samples. Results: A total of 20 SNPs were found in the CYP3A4 gene, including 11 known SNPs and nine novel SNPs. The known SNPs detected in our study were CYP3A4*1B, CYP3A4*1G, CYP3A4*10, CYP3A4*13, CYP3A4*14, CYP3A4*15, CYP3A4*17, CYP3A4*18, rs3091339, rs3091430 and rs28371761, and the novel SNPs were -658 A?C, G27A (E10K), T48A, G14284A (G167D), A15623G (N191D), C15635A (L196I), T15656C (F203L), G14199A (intron 5) and C15566T (intron 6). The allelic frequencies found in our sample varied from 1-37%. The novel SNPs detected in the CYP3A4 gene suggest that the Chinese population has different patterns of allele frequency compared with other populations. Conclusion: Several SNPs were detected in the CYP3A4 gene. The study of genetic variants in CYP3A4 may have an important significance for the understanding of genotype and phenotype relationships. [ABSTRACT FROM AUTHOR]

Aim: Extrapyramidal syndrome (EPS) is most commonly affected by typical antipsychotic drugs that have a high affinity with the D2 receptor. Recently, many research groups have reported on the positive relationship between the genetic variations in the DRD2 gene and the therapeutic response in schizophrenia patients as a result of the role of variations in the receptor in modulating receptor expression. In this study, we evaluate the role DRD2 plays in chlorpromazine-induced EPS in schizophrenic patients. Methods: We identified seven SNP(single nucleotidepolymorphism) (-141 Cins > del, TaqIB, TaqID, Ser311Cys, rs6275, rs6277 and TaqIA) in the DRD2 gene in 146 schizophrenic inpatients (59 with EPS and 87 without EPS according to the Simpson-Angus Scale) treated with chlorpromazine after 8 weeks. The alleles of all loci were determined by PCR (polymerase chain reaction). Results: Polymorphisms TaqID, Ser311Cys and rs6277 were not polymorphic in the population recruited in the present study. No statistical significance was found in the allele distribution of -141 Cins > del, TaqIB, rs6275 and TaqIA or in the estimated haplotypes (constituted by TaqIB, rs6275 and TaqIA) in linkage disequilibrium between the two groups. Conclusion: Our results did not lend strong support to the view that the genetic variation of the DRD2 gene plays a major role in the individually variable adverse effect induced by chlorpromazine, at least in Chinese patients with schizophrenia. Our results confirmed a previous study on the relationship between DRD2 and EPS in [ABSTRACT FROM AUTHOR]

It is known that in the pathogenesis of mental retardation (MR), both genetic and environmental factors (particularly iodine deficiency) appear to play a critical role. Transthyretin (TTR) transports between 20% and 30% of serum thyroxine in normal individuals and it is the main T4–binding protein in CSF. Variability in the TTR gene may influence risk for iodine–deficiency–based MR. The SNPs we selected from dbSNP were detected and identified using ARMS–PCR and sequencing methods, and we identified five novel sequence variants. Singular–locus association analysis indicated no association between the TTR gene and MR. In haplotype analysis, however, we found a haplotype CGTG+ (rs723744/G+6649C/T+6690C/rs2276382/del9) showed a weak positive association with MR ( χ 2 = 6.699, p = 0.035). Finally, we concluded that the weak positive result is more likely to be due to sampling error and the small size of this haplotype resulting from its relative low frequency. Our negative results provide no evidence that variants of TTR gene influence susceptibility to MR in the iodine–deficient areas of China and suggest that there may be a compensatory mechanism(s) in humans and mice, which work(s) to compensate the effect ofmutation in the TTR gene on MR. [ABSTRACT FROM AUTHOR]

Dysfunction of the N-methyl-D-aspartate (NMDA) receptors has been implicated in the etiology of schizophrenia based on psychotomimetic properties of several antagonists and on observation of genetic animal models. To conduct association analysis of the NMDA receptors in the Chinese population, we examined 16 reported SNPs across the NMDA receptor NR1 subunit gene (GRIN1) and NR2B subunit gene (GRIN2B), five of which were identified in the Chinese population. In this study, we combined universal DNA microarray and ligase detection reaction (LDR) for the purposes of association analysis, an approach we considered to be highly specific as well as offering a potentially high throughput of SNP genotyping. The association study was performed using 253 Chinese patients with schizophrenia and 140 Chinese control subjects. No significant frequency differences were found in the analysis of the alleles but some were found in the haplotypes of the GRIN2B gene. The interactions between the GRIN1 and GRIN2B genes were evaluated using the multifactor-dimensionality reduction (MDR) method, which showed a significant genetic interaction between the G1001C in the GRIN1 gene and the T4197C and T5988C polymorphisms in the GRIN2B gene. These findings suggest that the combined effects of the polymorphisms in the GRIN1 and GRIN2B genes might be involved in the etiology of schizophrenia. [ABSTRACT FROM AUTHOR]

Background : Iodine deficiency is common in the Qinba mountainous area and fetal iodine deficiency disorder (FIDD) is endemic. Our previous study demonstrated that apolipoprotein E (ApoE) was a genetic risk factor for FIDD in the local area. Aim : In order to achieve a better understanding of the aetiology of iodine deficiency-based mental retardation in the Qinba mountainous area, we conducted further studies of ApoE allele frequencies obtained from the local population. Subjects and methods : A total of 818 samples from four counties in the iodine-deficient area were recruited for the study of the ApoE genotype and allele frequencies using the PCR-RFLP method, and were subsequently confirmed by sequencing. Results : The frequencies of ε2, ε3 and ε4 alleles of Han Chinese in Qinba were 9.67%, 81.30% and 9.03%, respectively. Furthermore, no significant differences in the distribution of ApoE (either genotype or allele frequencies) between any two subgroups divided according to location, sex and age ( p > 0.05) were found. Surprisingly, however, we found a significant difference in the genotype and allele frequencies between Qinba and Shanghai (genotype: χ 2 = 14.91, p = 0.0096; allele: χ 2 = 15.07, p = 0.0009). Conclusion : The currently documented allele frequencies of ApoE in the Han Chinese population living in the open areas of China do not represent the distribution in the isolated Qinba mountainous area. The higher level of ε2 and ε4 allele frequencies in the Han Chinese living in the isolated Qinba area arise by chance or may result from genetic adaptation to an environment characterized by malnutrition and iodine deficiency, which may also contribute to the high incidence of mental retardation in these regions. [ABSTRACT FROM AUTHOR]

The genes (ABCC8 and KCNJ11) have a key role in glucose-stimulated insulin secretion and thus have always been considered as excellent susceptibility candidates for involvement in type 2 diabetes. Common polymorphisms (KCNJ11 E23K and ABCC8 exon16-3t/c) in these genes have been reported to be associated with type 2 diabetes in various European-descent populations. However, there were inconsistent results in previous studies in East Asian populations and no large case–control studies have been carried out in the Chinese Han population. In this study, these two variants were genotyped in about 4000 Chinese by using TaqMan technology on an ABI7900 system. A meta-analysis was also used to assess the results of association between the two variants and type 2 diabetes in East Asian populations. Our investigation confirmed the association between the KCNJ11 E23K variant and type 2 diabetes under a recessive model (KK vs EK+EE) in the Chinese Han population (odds ratio (OR)=1.25, 95% confidence interval (95% CI) 1.04–1.50, P=0.017). The meta-analysis of East Asian populations also showed a strong significant association of the K allele with diabetes (OR=1.15, P=3 × 10−9), whereas the exon16-3t/c variant (rs1799854) in ABCC8 showed no significant association. Thus, the common E23K variant is considered as a strong candidate for type 2 diabetes susceptibility across different ethnicities.Journal of Human Genetics (2009) 54, 433–435; doi:10.1038/jhg.2009.54; published online 5 June 2009 [ABSTRACT FROM AUTHOR]

A response by Liu and colleagues to a letter to the editor about their article "'FTO Gene Polymorphisms Are Associated With Obesity and Type 2 Diabetes in East Asian Populations: An Update" is presented.

Objectives: The 5-HT2A receptor is one of the most important serotonin receptors, serving as a major target for risperidone. Rs6311 and rs6313 polymorphisms in the HTR2A gene have been reported to be associated with response to risperidone treatment; however, many previous studies have yielded conflicting results. To confirm the importance of these polymorphisms in risperidone treatment and provide more evidence for the routine use of these pharmacogenetic biomarkers in clinical practice, we carried out an association analysis of rs6311 and rs6313 polymorphisms with risperidone efficacy in Chinese Han patients with schizophrenia. Methods: Two independent cohorts of unrelated subjects were recruited from Henan and Shanghai (95 and 113 subjects, respectively). After 4- or 8-week risperidone monotherapy, the rs6311 and rs6313 polymorphisms of these subjects were genotyped with direct DNA sequencing. Clinical improvement was measured by the reduction of the PANSS scores (including the total and subscale scores). UNIANOVA and case-control study was used to evaluate the effects of rs6311 and rs6313 polymorphisms on the therapeutic efficacy of risperidone. Results: As in previous studies, the rs6311G allele was found in complete linkage disequilibrium with the rs6313C allele. However, neither the rs6311 nor the rs6313 polymorphism significantly influenced clinical improvement during risperidone treatment. Neither the allele nor the genotype frequencies were significantly different between responder and non-responder subgroups. Conclusions: No significant association between HTR2A polymorphisms (rs6313 and rs6311) and risperidone efficacy was found in the present study. The relative large sample size and two independent cohorts of subjects in the present study enhance the reliability of our findings. [ABSTRACT FROM AUTHOR]

A common deletion comprising LCE3B and LCE3C, members of the late cornified envelope (LCE) gene cluster, has been shown to be significantly associated with psoriasis in several Caucasian populations. The expression of LCE can be induced by skin barrier disruption, leading to psoriatic lesions. To identify whether deletion of genes in the LCE region is a genetic risk factor in the pathogenesis of psoriasis, we genotyped the LCE3C and LCE3B deletion and single-nucleotide polymorphism rs4112788, which is in strong linkage disequilibrium with the LCE gene cluster, via direct sequencing in 468 psoriasis patients and 768 controls in a Chinese population. We found that deletion of the two LCE genes was associated with psoriasis (odds ratio=1.917; 95% confidence interval=1.291-2.847, P=0.001), a conclusion that was similar to that of another independent Chinese cohort study. The deletion was not significantly associated with the age of disease onset, and there was no significant epistatic interaction between deletion and PSORS1 risk allele on 6p21.3. Our study confirms an association between the deletion of LCE3C and LCE3B and psoriasis in a Chinese population. [ABSTRACT FROM AUTHOR]