神经型烟碱乙酰胆碱受体α7亚单位基因多态性与精神分裂症的传递不平衡研究

目的 探讨神经型烟碱乙酰胆碱受体α7亚单位基因(neuronal nicotinic acetyleholine receptor α7 subunit gene,CHRNA7)多态性与精神分裂症的关系.方法 应用聚合酶链反应及聚丙烯酰胺凝胶芯片技术检测129个精神分裂症先证者核心家系CHRNA7基因的rs2337980、rs1909884、rs883473三个单核苷酸多态性,并采用基于单倍型的单倍型相对风险检验(haplotype relative risk,HHRR)、传递不平衡检验(transmission disequilibrium test,TDT)及单倍型分析进行统计.结果 (1)HHRR分析结果显示rs2337980位点精神分裂症患者组与虚拟对照组之间等位基因频率差异有统计学意义(P=0.017);(2)TDT分析发现,rs2337980位点与精神分裂症之间可能存在传递不平衡,杂合子父母过多的传递等位基因C给患病子女(P=0.021).(3)单倍型分析发现,rs2337980、rsl909884及rs2337980、rsl909884、rs883473组成的单倍型与精神分裂症有显著相关(总体P=0.034;glohal P=0.027),其中T-C,T-C-T两个单倍型与精神分裂症可能存在传递不平衡.结论 CHRNA7 基因多态性可能与精神分裂症存在关联,rs2337980的变异等位基因T可能是精神分裂症的保护性因子.     

ESR1基因单核苷酸多态性及单倍型与精神分裂症的关联研究

目的 探索雌激素受体1 (estrogen receptor 1,ESR1)基因rs2234693、rs9340799和rs3798759位点单核苷酸多念性(single nucleotide polymorphisms,SNPs)及其单倍型与精神分裂症(schizophrenia,SZ)发病之间的相关性.方法 应用聚合酶链反应-限制性片段长度多态性技术对333例SZ患者和315名正常对照rs2234693、rs9340799和rs3798759位点进行基因分型,应用x2检验对SZ组和对照组等位基因、基因型和单倍型频率进行分析.结果 rs2234693、rs9340799位点两组间基因型频率及等位基因分布差异均无统计学意义(P＞0.05).SZ组rs3798759位点GG基因型频率及G等位基因频率均高于健康对照组(P＜0.01).性别分层分析提示,女性SZ患者rs3798759位点TG、GG基因型频率及G等位基因频率均高于健康女性(P＜0.05).单倍型C-A-G和C-G-G在SZ组的分布频率高于对照组(P＜0.05).结论 rs3798759位点突变可能为女性精神分裂症发生的风险因子,C-A-G和C-G-G单倍型可能为精神分裂症的遗传风险单倍型.     

Neuregulin 1基因多态性与中国汉族精神分裂症关联分析

目的 探讨Neuregulin 1(NRG1)基因多态性与精神分裂症的关联.方法 在258个中国汉族精神分裂症核心家系(患者及其亲生父母)中,应用实时定量PCR技术检测位于NRGl基因5'端的4个单核苷酸多态(single nucleotide polymorphism,SNP)位点:rs221533(C/T)、rs7820838(C/T)、433E1006 (A/G)和rs3924999(C/T),进行基因分型,应用传递不平衡检测(transmission disequilibrium test,TDT)分析等位基因传递情况,分析该基因与精神分裂症易感性的关联.结果 在258个中国汉族核心家系中,rs221533、433E1006、rs3924999三个SNP均存在有统计学意义的传递不平衡,优先传递的等位基因分别是:C、A、T(rs221533:X2=27.45,P=0.000;433E1006:X2=56.08,P=0.000;rs3924999:X2=10.53,P=0.001).rs7820838未检到不平衡传递(X2=3.31,P=0.081).频率大于1%单倍型进行分析,rs221533-rs7820838-433E1006联合分析,单倍型C/C/G和C/C/A优先传递(C/C/G:X2=5.26,P=45.08;C/C/A:X2=0.026,P=0.000);rs221533-rs7820838-433E1006-rs3924999联合分析,单倍型C/C/G/T、C/C/A/C和C/C/A/T优势传递(C/C/G/T:X2=10.71,P=0.001;C/C/A/C:.)X2=8.83,P=0.006、C/C/A/T:X2=27.00,P=0.000).213个阳性亚型的精神分裂症核心家系中传递不平衡得出基本一致的结果 .结论 Nrg1基因多态性与中国汉族人群精神分裂症存在关联,尤其是支持与阳性亚型精神分裂症存在关联.     

内皮固有型一氧化氮合酶基因单核苷酸多态性与冠心病的相关性研究

探讨内皮固有型一氧化氮合酶(ecNOS)基因的单核苷酸多态性(SNP)与冠心病(CAD)的相关性.提取107例CAD患者和132名健康对照者外周血有核细胞DNA,应用荧光标记单碱基延伸分型技术及寡核苷酸微阵列芯片杂交技术检测ecNOS基因的2个标签SNP(tag SNP)rs7830和rs3918188.结果发现CAD组rs7830的CC基因型频率和C等位基因频率明显低于健康对照组(P＜0.05).两组rs3918188的基因型频率及等位基因频率无统计学差异(P＞0.05).通过对2个SNP进行单倍型分析发现,CAD组和健康对照组的单倍型频率具有统计学差异(P<0.05).结果提示ecNOS基因 rs7830多态性变异及由rs7830和rs3918188构建的CA、AA单倍型是CAD的遗传危险因素.     

基质金属蛋白酶-3基因多态性与脑卒中亚型的相关性

目的 探讨中国北方汉族人群基质金属蛋白酶-3(matrix metalloproteinase-3,MMP-3)基因多态性与缺血性脑卒中(ischemic stroke,IS)亚型的相关性.方法 应用病例对照研究,选取289例急性缺血性脑卒中患者(发病≤3d)和175名同期健康体检者.卒中组按急性卒中治疗低分子肝素试验病因分型法分为大动脉粥样硬化性(large artery atherosclerotic,LAA)脑卒中185例,小动脉闭塞性(small artery occlusion,SAO)脑卒中104例.选取MMP-3基因rs3025058(-11715A/6A),rs522616(-709A/G)及rs679620(133A/G)3个常见单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点,应用聚合酶链反应限制性片段长度多态性或直接测序法对MMP-3基因3个SNP位点进行基因分型.结果 3个位点存在不完全连锁不平衡,且基因多态性均与LAA型脑卒中相关(P＜0.05).在显性模型中,rs3025058位点5A5A+5A6A基因型携带者患LAA型脑卒中的风险是6A6A基因型携带者的1.72倍(P=0.017,OR=1.72,95％CI:1.10～2.69);rs522616位点GG+ AG基因型携带者患LAA型脑卒中的风险是AA基因型携带者的0.52倍(P=0.005,OR=0.52,95％CI:0.33～0.82);rs679620位点AA+ GA基因型携带者患LAA型脑卒中的风险是AA基因型携带者的1.55倍(P=0.042,OR=1.55,95％CI:1.01～2.37).但是,3个SNPs基因型和等位基因频率在对照组与SAO型脑卒中之间差异无统计学意义(P＞0.05).另外,LAA组5A-A-A及6A-A-A单倍型高于对照组,差异有统计学意义(P＜0.05),而6A-G-G单倍型显著低于对照组(P＜0.01).结论 MMP-3血清水平在LAA型脑卒中急性期增高明显,SAO型脑卒中次之;中国北方汉族人群MMP-3基因rs3025058,rs522616及rs679620多态性可能与LAA型脑卒中易感性相关.     

IRF6基因rs2235371位点多态性与非综合征性唇裂伴或不伴腭裂的相关性研究

目的 探讨干扰素调节因子6 (interferon regulatory factor 6,IRF6)基因rs2235371位点820G＞A单核苷酸多态性与非综合征性唇裂伴或不伴腭裂(nonsyndromic cleft lip with or without cleft palate,NSCL士P)的相关性.方法 收集106例患者及其父母以及129名对照及其父母的核心家庭标本,用聚合酶链反应-限制性片段长度多态性的方法进行IRF6基因rs2235371位点单核苷酸多态性检测;用人群关联研究、传递不平衡检验(transmission disequilibrium test,TDT)、单倍型相对风险率(haplotype-based haplotype relative risk,HHRR)、家系为基础的关联检验(family-based association tests,FBAT)等方法进行统计分析.结果 病例组与对照组相比,子代的基因型分布差异无统计学意义(P＞0.05),而等位基因频率比较差异有统计学意义(P＜0.05);母亲组基因型分布差异有统计学意义(P＜0.05);按唇腭裂类型分类后,单纯唇裂组子代基因型分布和等位基因的频率与对照组相比差异均有统计学意义(P＜0.05);而唇腭裂组基因型分布和等位基因频率差异均无统计学意义(P＞0.05).传递不平衡检验提示,rs2235371位点的G等位基因在NSCL±P核心家庭中存在传递不平衡(x2=5.56,P=0.024).HHRR检验x2=5.115,P=0.024,OR=1.674,95％CI:1.069～2.621;FBAT检验Z=2.218,P=0.027.结论 在中国北方人群中IRF6基因rs2235371位点突变与非综合征性唇腭裂存在关联.     

抑郁症与cAMP反应元件结合蛋白基因的关联研究

目的 探讨cAMP反应元件结合蛋白(cyclic adenosine monophosphate response elementbinding protein,CREB1)基因与抑郁症的关联关系.方法 采用聚合酶链反应-限制性片段长度多态性方法检测105个抑郁症核心家系CREB1基因上单核苷酸多态性(single nucleotide polymorphisms,SNP)rs10932201和rs6740584的等位基因与基因型分布情况.进行单位点及单倍型的传递/不平衡检验(transmission disequilibrium test,TDT).结果 CREB1基因上SNP位点rs10932201和rs6740584与抑郁症均无显著性关联,TDT χ2 值分别为2.700(P=0.1004)和0.458(P=0.4986),差异均无统计学意义.单倍型TDT分析结果显示由rs10932201和rs6740584构成的单倍型与抑郁症存在显著性关联,差异有统计学意义(总χ2=23.458,df=3,P=0.00003241).单个单倍型A-C和A-T与抑郁症也均有显著性关联,差异有统计学意义(χ2 值分别为5.405和13.623,P值分别为0.020和0.00022).结论 CREB1基因上SNP位点rs10932201和rs6740584与抑郁症均无显著性关联,但由这2个SNP位点构成的单倍型与抑郁症存在显著性关联,提示CREB1基因rs10932201-rs6740584单倍型可能在抑郁症的遗传学发病机制中具有重要作用.     

广西壮族男性膜型基质金属蛋白酶1基因多态性与骨质疏松症的相关性

目的 探索膜型基质金属蛋白酶1(membrane-type l matrix metalloproteinase,MTl-MMP,MMP14)基因的多态性与广西百色地区壮族男性骨质疏松症的相关性.方法 用超声骨密度仪测量百色地区301名壮族男性左跟骨超声振幅衰减(broadband ultrasonic attenuation,BUA),并根据中国人骨质疏松症建议诊断标准分为正常对照、骨量减少以及骨质疏松组.应用Multiplex SNaPshot SNP分型技术确定MMP14基因5个单核苷酸多态性(single nucleotide polymorphism,SNP)位点(rs1003349、rs3751488、rs2269213、rs2236303和rs743257)的基因型.结果 全部位点的多态性分布均符合Hardy-Weinberg平衡(P＞0.05).多元线性逐步回归分析提示,上述多态性与BUA变异无相关性(P＞0.05).rs2236303位点CC基因型(vs.TT,OR=10.604,95％CI:1.899～59.228,P=0.007)、CT基因型(vs.TT,OR=5.602,95％CI:1.351～23.24,P=0.018)以及rs1003349的GT基因型(vs.GG,OR=4.884,95 ％CI;1.087～21.949,P=0.039)在骨质疏松组的频率显著偏高.连锁不平衡分析显示,rs1003349和rs2236303位点存在一般连锁(D′=0.839,r2 =0.458,P＜0.01),两个位点的单倍型G-T在骨量正常组与骨质疏松组中的频率差异有统计学意义(P＜0.05),单倍型为G-T的个体发生骨质疏松症的风险显著高于G-C或T-C的个体(P＜0.05).结论 MMP14基因的rs1003349和rs2236303多态性位点可能与广西壮族男性骨质疏松症的易感性相关,rs1003349和rs2236303位点的单倍型G-C和T-C可能增加骨质疏松症的发病风险.     

腺苷A1受体基因与精神分裂症的遗传关联分析

目的探讨腺苷A1受体基因(ADORA1)多态性与精神分裂症关联的关系。方法选取ADORA1基因上rs3766558位点采用聚合酶链式反应—限制性片段长度多态性(PCR-RFLP)方法对119例精神分裂症病例,包括88例正常对照组ADORA1基因分型进行检测和进行遗传关联分析。结果病例组和正常对照组基因型分布符合Hard-Weinberg平衡法则,rs3766558单倍型相对风险分析,结果为χ2=6.301,P=0.026和χ2=4.771,P=0.029。差异到达显著(P<0.05)。结论漳州地区人群ADORA1基因rs3766558与精神分裂症存在关联。     

基于家系的Tim-3基因多态性与儿童变应性哮喘的关联研究

目的 以家系资料为基础,利用遗传不平衡原理探讨染色体5q33.2区Tim-3基因启动子两个多态性位点rs10053538和rs10515746与中国湖北地区汉族儿童变应性哮喘的关系.方法 应用限制性片段长度多态性技术结合测序方法,分析了118个儿童变应性哮喘核心家系Tim-3基因rs10053538和rs10515746的基因型;采用基于家系的关联分析方法,包括单体型相对风险分析(HRR)和传递不平衡检验(TDT),分析基因分型数据;应用Transmit软件构建单体型并进行单体型关联分析.结果 118个核心家庭HRR分析显示Tim-3基因启动子区两个多态性位点rs10053538和rs10515746不使病人具有更高的发病风险(X2=2.430,P>0.05;x2=1.368,P>0.05).118个满足经典TDT分析的核心家庭中,杂合子父母传递给患病子代的等位基因频率不比预期值高(x2=2.042,P>O.05;x2=0.750,P>O.05).Transmit双位点单体型分析也未见父母传递给子女各个单体型的观察值和期望值有明显差异(P>O.05).结论 中国湖北地区汉族人群中,Tim-3基因启动子区两个多态性位点rs10053538和rs10515746与儿童变应性哮喘不具有相关性.     

A genetic association study of the FXYD domain containing ion transport regulator 6 (FXYD6) gene, encoding phosphohippolin, in susceptibility to schizophrenia in a Japanese population

The FXYD domain containing ion transport regulator 6 (FXYD6) gene is located within a region of chromosome 11 (11q23.3) that has been shown by a number of genome scans to be one of the most well-established linkages to schizophrenia. FXYD6 encodes the protein phosphohippolin, which is primarily expressed in the brain. Phosphohippolin modulates the kinetic activity of Na,K-ATPase and has long-term physiological importance in maintaining cation homeostasis. A recent study reported that FXYD6 was associated with schizophrenia in the United Kingdom samples. Applying the gene-based association concept, we carried out an association study regarding FXYD6 and schizophrenia in a Japanese population, with a sample consisting of 2026 subjects (906 schizophrenics and 1120 controls). After linkage disequilibrium analysis, 23 single nucleotide polymorphisms (SNPs) were genotyped using 5'-exonuclease allelic discrimination assay. We found a significant association of two SNPs (rs11216573; genotypic P value: 0.022 and rs555577; genotypic P value: 0.026, allelic P value: 0.011, uncorrected). Nominal P values did not survive correction for multiple testing (rs11216573; genotypic P value: 0.47 and rs555577; genotypic P value: 0.55, allelic P value: 0.24, after SNPSpD correction). No association was observed between schizophrenia patients and controls in allelic, genotypic and haplotypic analyses. Our findings suggest that FXYD6 is unlikely to be related to the development of schizophrenia in a Japanese population.     

Confirmation of the genetic association between the U2AF homology motif (UHM) kinase 1 (UHMK1) gene and schizophrenia on chromosome 1q23.3

UHMK1 has previously been implicated as a susceptibility gene for schizophrenia in the 1q23.3 region by significant evidence of allelic and haplotypic association between schizophrenia and several genetic markers at UHMK1 in a London-based case-control sample. Further fine mapping of the UHMK1 gene locus in the University College London schizophrenia case-control sample was carried out with tagging SNPs. Two additional SNPs were found to be associated with schizophrenia (rs6604863 P = 0.02, rs10753578 P = 0.017). Tests of allelic and haplotypic association were then carried out in a second independent sample from Aberdeen consisting of 858 individuals with schizophrenia and 591 controls. Two of these SNPs also showed association in the Aberdeen sample (rs7513662 P = 0.0087, rs10753578 P = 0.022) and several haplotypes were associated (global permutation P = 0.0004). When the UCL and Aberdeen samples were combined three SNPs (rs7513662 P = 0.0007, rs6427680 P = 0.0252, rs6694863 P = 0.015) and several haplotypes showed association (eg HAP-A, HAP-B, HAP-C permutation P = 0.00005). The finding of allelic association with markers in the UHMK1 gene might help explain why it has not been possible, despite great effort, to satisfactorily confirm previously reported associations between schizophrenia and the genes RGS4 and NOS1AP/CAPON. These genes flank UHMK1 and all three loci are within a 700 kb region showing linkage to schizophrenia. The confirmation of association between UHMK1 and schizophrenia, rather than RGS4 and NOS1AP in the London sample, points to the possibility that previous efforts to accurately fine map a gene in the 1q23.3 region have lacked accuracy or may have suffered from methodological flaws.     

Functional genetic variation at the NRGN gene and schizophrenia: evidence from a gene-based case-control study and gene expression analysis

Genome-wide association and follow-up studies have reported an association between schizophrenia and rs12807809 of the NRGN gene on chromosome 11q24.2. We investigated the association of five linkage disequilibrium-tagging SNPs and haplotypes that cover the NRGN gene with schizophrenia in a Japanese sample of 2,019 schizophrenia patients and 2,574 controls to determine whether rs12807809 is the most strongly associated variant for schizophrenia in the vicinity of the NRGN gene. We found that the rs12807809-rs12278912 haplotype of the NRGN gene was associated with schizophrenia (global P = 0.0042). The frequencies of the TG and TA haplotypes of rs12807809-rs12278912 in patients were higher (OR = 1.14, P = 0.0019) and lower (OR = 0.85, P = 0.0053), respectively, than in the controls. We did not detect any evidence of association of schizophrenia with any SNPs; however, two nominal associations of rs12278912 (OR = 1.10, P = 0.057) and rs2075713 (OR = 1.10, P = 0.057) were observed. Furthermore, we detected an association between the rs12807809-rs12278912 haplotype and NRGN expression in immortalized lymphoblasts derived from 45 HapMap JPT subjects (z = 2.69, P = 0.007) and confirmed the association in immortalized lymphoblasts derived from 42 patients with schizophrenia and 44 healthy controls (z = 3.09, P = 0.002). The expression of the high-risk TG haplotype was significantly lower than the protective TA haplotype. The expression was lower in patients with schizophrenia than in controls; however, this difference was not statistically significant. This study provides further evidence of the association of the NRGN gene with schizophrenia, and our results suggest that there is a link between the TG haplotype of rs12807809-rs12278912, decreased expression of NRGN and risk of developing schizophrenia.     

A family-based association study of the myelin-associated glycoprotein and 2',3'-cyclic nucleotide 3'-phosphodiesterase genes with schizophrenia

A recent surge of evidence implicating myelin abnormalities in the etiology of schizophrenia has been found. This study is a family-based genetic association analysis examining the myelin-associated glycoprotein (MAG) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) genes in schizophrenia. About 246 families of primarily European-Caucasian origin were genotyped for MAG rs2301600, rs720308, rs720309, rs756796, and CNP rs2070106 single nucleotide polymorphisms (SNPs). The FBAT program (v1.7.2) and Transmit were used to analyze individual SNPs and haplotypes, respectively. The CNP SNP (rs2070106) was potentially associated with schizophrenia (P=0.027). MAG variants were not associated with disease transmission based on single marker or haplotype analysis. A significant maternal parent-of-origin effect for the CNP risk allele for schizophrenia was found (P=0.003). No CNP-MAG gene-gene interaction conferred increased risk for schizophrenia. Our finding provides support for potential association of the CNP gene but not the MAG gene in schizophrenia in a Caucasian population.     

Association study between the TNXB locus and schizophrenia in a Japanese population.

The chromosome 6p21-24 region, which contains the human leukocyte antigen (HLA) region, has been suggested as an important locus for a susceptibility gene for schizophrenia. Recently, a significant association between schizophrenia and the TNXB locus, located immediately telomeric of the NOTCH4 locus in the HLA region, was observed. Few studies have further investigated the region in schizophrenia. In the present study, we investigated the region in a Japanese population. Subjects included 241 patients with schizophrenia and 290 controls. Twenty-six single nucleotide polymorphisms (SNPs) and the corresponding haplotypes were analyzed. As a result, exactly the same SNPs in the TNXB locus (rs1009382 and rs204887) as in the previous study were associated with schizophrenia (P = 0.034 and 0.034, respectively, uncorrected). A SNP (rs2071287) in the NOTCH4 locus and haplotype around it were also suggested to associate with the disease, consistent with another previous study (P = 0.041 and permutation P = 0.024, respectively, uncorrected). Although these associations became insignificant after Bonferroni correction, the findings might provide support for the association of the TNXB locus or its adjacent region of the NOTCH4 locus with schizophrenia.     

Polymorphisms of myelin-associated glycoprotein gene are associated with schizophrenia in the Chinese Han population

Results of gene expression microarray and quantitative PCR studies have suggested abnormalities in the expression of myelin-related genes including myelin-associated glycoprotein (MAG) in schizophrenic patients. Research provides strong evidence for oligodendrocyte dysfunction in schizophrenics. In order to further assess the role of MAG in schizophrenia, we examined four single nucleotide polymorphisms (SNPs), namely rs2301600, rs3746248, rs720309 and rs720308, of this gene in Chinese schizophrenic patients (n=470) and healthy controls (n=470). The distribution of rs720309 T/A genotypes showed a strong association with schizophrenia (chi(2)=14.58, d.f.=2, P=0.0008). A haplotype constructed of rs720309-rs720308 also revealed a significant association with schizophrenia (chi(2)=11.914, d.f.=3, P=0.0084). Our findings of a significant associations between schizophrenia and the MAG gene suggest that this gene may be involved in susceptibility to schizophrenia in the Chinese Han population.     

AXIN2基因三个位点与先天性巨结肠的关联研究

目的 探讨AXIN2基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)rs2240308、rs8081536和rs9913621 3个位点与先天性巨结肠(Hirschspnmg disease,HSCR)的关联性.方法 对120例HSCR患者和120名正常人群外周血进行基因组DNA抽提,用PCR技术对AXe2基因3个位点(rs2240308、rs8081536和rs9913621)进行PCR扩增,PCR产物用内切酶CviJ I、Dde I和BaN I消化,将SNPs位点进行分型与分析,应用X2检验统计分析病例组和对照组等位基因频率、等位基因型频率及其患病风险;同时将PCR产物进行测序,以进一步确定基因突变位点.结果 HSCR组与对照组AXIN2 rs8081536 CC和CT基因型频率差异无统计学意义(P＞0.05);而HSCR组与对照组AXIN2 rs2240308 GG、AG和从基因型频率及A和G等位基因频率差异有统计学意义(P＜0.05),GC和从基因型及G等位基因的患病风险分别为2.091、0.846和1.703;HSCR组与对照组AXIN2 rs9913621 CC、CT和TT基因型频率及C和T等位基因频率差异有统计学意义(P＜0.05),CC和TT基因型及T等位基因的患病风险分别为0.535、1.113和1.569.测序rs2240308第301位密码子核苷酸GCA→CCA杂合突变;rs913621第199位密码子核苷酸CAC→CAG杂合突变.结论 AXIN2 rs8081536等位基因变异与HSCR的易感性无关;AXIN2 rs2240308和rs9913621与HSCR的发生可能有关联,具有GG基因型与CC基因型患HSCR的危险性相对较高.     

网状内皮素4受体基因多态性与中国汉族精神分裂症关联分析

目的:分析网状内皮素4受体(RTN4R)基因上的5个单核苷酸多态性(SNP)与中国汉族精神分裂症关联,探讨RTN4R基因单核苷酸多态性与精神分裂症易感性的关系。方法:收集符合美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)诊断的528名偏执型精神分裂症患者,在同一地域招募健康体检者528名作为对照,并采用阳性与阴性症状量表(PANSS)评估234例首次发病患者的临床症状,采用基因分型芯片对RTN4R基因上的5个功能单核苷酸多态性位点进行基因分型,分析多态性与疾病的关联性,以及PANSS因子分与RTN4R多态性的关联。结果:成功检测5个单核苷酸多态性位点的基因型,关联分析显示这些位点基因型和等位基因频率分布病例和对照之间差异无统计学意义。与携带rs696880位点GG基因型患者相比,携带AA基因型患者PANSS阳性分[(23.5±5.6)vs.(25.1±7.6),P0.05]、一般精神病理症状分[(42.6±9.9)vs.(46.0±13.4),P0.05]均较低,携带AA基因型患者发病年龄晚于携带GG型患者[(24.9±8.1)岁vs.(22.2±6.2)岁,P0.05]。结论:在中国汉族人群中,RTN4R基因多态性与精神分裂症可能不存在关联,但可能影响疾病表现。     

DTNBP1基因rs4715986位点多态性与中国汉族人群偏执型精神分裂症相关

目的通过两步法研究中国汉族人群DTNBP1基因的多态性与偏执型精神分裂症的相关性。方法发现阶段:在532例偏执型精神分裂症患者及488名健康对照中使用Sanger测序方法检测DTNBP1的11个SNP位点。验证阶段:在1 111例偏执型精神分裂症患者及1 435名健康对照中使用Taqman探针分型的方法对发现阶段检出阳性的rs4715986位点进行验证。结果发现DTNBP1中的rs4715986位点与偏执型精神分裂症的高患病风险相关(χ~2=11.02,P0.01)。在验证人群中重复出rs4715986与偏执型精神分裂症的相关性(χ~2=9.29,P=0.01)。结论DTNBP1基因rs4715986位点的多态性与偏执型精神分裂症的高患病风险相关。DTNBP1可能是中国汉族人群偏执型精神分裂症的易感基因。     

EMILIN1基因多态性与蒙古族原发性高血压相关性研究

目的 探讨蒙古族人群中EMILIN1基因的3个单核苷酸多态性(single nucleotide polymorphism,SNP)位点与原发性高血压的关系.方法 在内蒙古自治区蒙古族人群中选取201例原发性高血压患者和202名血压正常者进行病例对照研究,应用聚合酶链反应-限制性片段长度多态方法检测rs3754734、rs2011616和rs2304682这3个SNP位点的等位基因和基因型分布,并构建单倍型.结果 在这3个SNP位点中,rs2304682位点的基因频率和基因型频率在高血压组和对照组间差异有统计学意义(P＜0.05),并且在rs3754734和rs2304682这2个SNP位点构建的单倍型中,G-C和G-G单倍型在高血压组和对照组之间差异有统计学意义(P＜0.05).在舒张压偏高组和舒张压正常组间,rs2304682位点的基因型和等位基因分布差异有统计学意义(P＜0.05),而在收缩压偏高组和收缩压正常组间,各个SNP的基因型和等位基因分布差异无统计学意义(P＞0.05).结论 在蒙古族人群中,EMILIN1基因rs2304682多态性位点以及rs3754734和rs2304682这2个SNP位点构建的G-G单倍型可能与原发性高血压的易感相关联,rs2304682的多态性与蒙古族原发性高血压的舒张压的高低可能有关联.

Abstract：

Objective To explore the relationship between genetic polyrnorphisms of 3 single nucleotide polymorphisms (SNPs) in the elastin microfibril interfacer 1 (EMILIN1)gene and essential hypertension. Methods A case-control study was conducted in which 201 hypertensive patients and 202 healthy controls in Mongolian population were enrolled, and the genotypes of rs3754734, rs2011616 and rs2304682 loci were analyzed using polymerase chain reaction-restriction fragment length polyrnorphism (PCR-RFLP) and direct sequencing techniques. Results There were significant differences in the frequencies of alleles and genotypes for the rs2304682 between the hypertensives and normotensives in the population(P＜0. 05). The frequency of the G-G haplotype established by rs3754734 and rs2304682 was significantly higher in the hypertensive patients (P＜0. 05). The frequencies of alleles and genotypes for the rs2304682 also had significant differences between the group with high diastolic blood pressure and normal diastolic blood pressure (P＜0.05). There were no significant differences in the frequencies of alleles and genotypes for the 3 SNPs between the group with high systolic blood pressure and normal systolic blood pressure (P＞0.05). Conclusion The rs2304682 locus in the EMILIN1 gene, as well as the haplotypes G-G constructed using rs3754734 and rs2304682, may associate with the susceptibility of essential hypertension in the Mongolian population. Also, rs2304682 may associate with the level of the diastolic blood pressure.