广州地区汉族人群多巴胺受体基因多态性

目的 探讨广州地区汉族人群多巴胺Ｄ２（ＤＲＤ２）、Ｄ５（ＤＲＤ５）受体基因的多态性分布规律。方法 用聚合酶链反应－限制性片段长度多态性和聚合酶链反应－等位基因特异性扩增技术对１４１名广州地区汉族人的ＤＲＤ２、ＤＲＤ３、ＤＲＤ５基因多态性进行了检测,并与其他人群做了比较。结果 ＤＲＤ２基因３’端非翻译区的Ｔａｑ１Ａ突变点Ａ１（ＴａｑＩ－）、Ａ２（ＴａｑＩ＋）等位基因频率分别为４８％和５２％;Ａ１Ａ１     

NURR1基因多态性与帕金森病的关联研究

目的 了解NURR1基因多态性与四川地区散发性帕金森病之间的相关性.方法 采用病例-对照研究,应用聚合酶链反应、等位基因特异性、限制性片段长度多态性对四川地区汉族人群241例帕金森病患者和236名正常对照NURR1基冈启动子区的c.-2922(C)2-3及第6内含子的ⅣS6+18imG多态位点进行关联分析.结果 IVS6+18insG位点帕金森病组3G/3G,3G/2G,2G/2G基因型频率与对照组相比差异无统计学意义(X2=3.733,P=0.155).进一步按发病年龄分层后发现,50岁以前发病的帕金森病患者基因型频率与对照组之间差异有统计学意义(X2=6.545,P=0.038).发病年龄＜50岁的帕金森病组患者3G/2G基因型频率显著高于对照组(54.12%vs 38.14%),并且与其他两组基因型合并相比差异有统计学意义(X2=6.537,P=0.011;OR=1.913,95%CI:1.159～3.158).c.-2922(C)2-3位点帕金森病组与对照组相比3C/3C,3C/2C及2C/2C基因型频率差异无统计学意义(P=0.766).结论 本研究结果提示NURR1基因ⅣS6+18insG多态可能与本组人群早发性帕金森病的遗传易感性相关;未发现c.-2922(C)2-3位点多态性与本组人群帕金森病的遗传易感性相关.     

中国人C4重复基因座位初探

从78个家系266人次中研究了中国人C4基因的重复情况。在78个家系中有7个家系成员表现C4基因重复,占9.0%;依人头计,在266人中有17人C4基因表现重复,占6.4%。这17人均为C4B 基因重复,重复的类型及人数分别为,①C4B(1,2):2人,②B(1,12):6人;③B(1,1):5人;④B(1,96,96):2人;⑤B(2,2):2人。     

中国人自身免疫性肝病相关性 CTLA-4基因多态性研究

目的　探讨细胞毒性 T细胞相关抗原 - 4 (cytotoxic T lymphocyte- associated antigen- 4 ,CTL A- 4 )基因启动子 - 318和第 1外显子区第 4 9位基因多态性与中国人自身免疫性肝炎 (autoimmunehepatitis,AIH)、原发性胆汁性肝硬化 (primary biliary cirrhosis,PBC)发病的相关性。方法　应用限制性片段长度多态性方法分析 6 2例 AIH和 77例 PBC患者外周血单核细胞基因组 DNA CTL A- 4启动子 -318T/ C、第 1外显子区第 4 9位基因 A/ G多态性 ,并与 16 0名正常对照比较。结果　 AIH组 CTL A- 4启动子 - 318位 T/ C基因型分布与对照组比较差异无显著性 ,但 C等位基因频率明显高于正常对照组 (P=0 .0 2 ,OR=2 .4 3)。 PBC患者 CTL A- 4第 1外显子区第 4 9等位基因分布与正常对照组比较差异非常显著(P=0 .0 0 6 ) ,PBC患者 G等位基因频率明显高于正常组 (P=0 .0 0 4 6 ,OR=1.8)。联合分析 CTL A- 4启动子与第 1外显子的基因多态性分布 ,虽然 AIH组和 PBC组 GG- CC型携带率均比正常人高 (AIH组 :32 .3% ,PBC组 :37.7% ,对照组 :2 2 .5 % ) ,但是统计学分析结果均显示两组患者与正常人差异无显著性。结论　 CTL A- 4启动子 - 318和第 1外显子区第 4 9位基因多态性可能与中国人 AIH、PBC易感性相关。     

多巴胺D2受体基因启动子多态性与帕金森病的关联研究

目的 探讨中国汉族人群多巴胺D2受体基因启动子多态性在帕金森病（Parkinson's disease,PD)遗传易感性中的作用。方法 采用病例－对照关联分析，聚合酶链反应－限制性片段长度多态性方法分析了123例PD患者（PD组）与124名健康成人（对照组）多巴胺D2受体基因启动子多态性。结果 PD组－141△C等位基因频率为8．5％，对照组为11．7％；两组差异无显著性（P＞0．05）；中国汉族人PD组组和对照组－141△C等位基因频率明显高于意大利南部人群，差异有显著性（P＜0．05）。结论中国汉族人群多巴胺D2受体基因启动子多态性与PD的遗传易感性无关，该多态性有明显的种族差异。     

DJ-1基因多态性与四川地区散发性帕金森病的相关性研究

目的 了解DJ-1基因3个多态位点(g.168-185del;SNP405,refSNPID:rs3766606;293G/A)的频率以及与帕金森病的相关性.方法 采用病例-对照研究,应用聚合酶链反应-限制性片段长度多态性及DNA测序等技术对192例帕金森病患者和198名对照者的3个位点进行基因型的检测.结果 在g.168-185del位点,研究人群中Ins/Ins基因型较普遍,等位基因Del的频率很低(0.38%);在所检测的人群中未发现293G/A的多态性.上述结果与欧美国家的报道不一致.在SNP405 G/T多态位点中,在发病年龄小于40岁的帕金森患者群中G/T基因型频率显著高于对照组(18.75%vs5.54%,P=0.004,OR=6.30,95%CI:1.96～20.18).结论 g.168-185del和293G/A两多态性位点的频率在中国人群与欧美人群间可能存在差异;非翻译区SNP405 G/T多态性可能增加早发帕金森病的发病风险.     

多巴胺β羟化酶基因多态性与帕金森病遗传易感性

目的 探讨多巴胺β羟化酶(dopamine beta hydroxylase,DBH)基因内含子5Taq I多态性与帕金森病遗传易感性的关系。方法 用聚合酶链反应—限制性长度片段多态性技术检测了144例原发性帕金森病患者和年龄及性别相匹配的188名健康人多巴胺β羟化酶基因内含子5Taq I多态性。结果 与健康人比较，帕金森病患者DBH基因内含子5Taq I基因型(A1／A2，A2／A2)或等位基因(A1，A2)的分布不同，两组之间的差异有显著性(基因型：A1／A2 OR＝0．45，Z＝10．11，P＜0．015 A2／A2 OR＝2．11，Z＝10．66，P＜0．01；等位基因：A1 OR＝0．54，Z＝10．20，P＜0．01；A2 OR＝1．82，Z＝10．89，P＜0．01)。结论 DBH基因Taq I多态性可能在帕金森病的遗传易感性中起作用。     

中国广西人群中RTN4基因遗传多态性的研究

目的:研究RTN4基因rs2920891A/C和rs17046647A/G位点多态性在广西人群中的分布特征,比较不同人群的分布差异。方法:本实验采用多重单碱基延伸PCR(SNa Pshot)和DNA测序方法,对323例广西健康体检者RTN4基因的rs2920891A/C和rs17046647A/G位点基因型进行检测,并与国际人类基因组单体型图计划(Hap Map)公布的不同人群(北京、日本、欧洲及非洲人群)RTN4基因多态性数据进行比较。结果:在广西人群中,RTN4基因rs2920891A/C位点存在AA、AC、CC基因型及A、C等位基因,其等位基因频率在男女间的分布差异有统计学意义(P0.05),基因型及等位基因频率与日本、欧洲及非洲人群比较差异均有统计学意义(P0.05);rs17046647A/G位点存在AA、AG、GG基因型和A、G等位基因,基因型及等位基因频率在男女间比较差异无统计学意义(P0.05),而与日本、欧洲及非洲人群比较差异均有统计学意义(P0.01)。结论:中国广西人群中RTN4基因的rs2920891A/C和rs17046647A/G位点多态性与其他种族间存在差异性。     

Failure to replicate association between the gene for the neuronal nicotinic acetylcholine receptor α4 subunit (CHRNA4) and IGE

The gene for the neuronal nicotinic acetylcholine receptor α4 subunit (CHRNA4) was identified as a gene underlying a rare idiopathic partial epilepsy syndrome in humans, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In a recent study, one of four silent polymorphisms (594 C/T) in CHRNA4 showed association with the common subtypes of idiopathic generalised epilepsy (IGE). In the present study, three of these polymorphisms were investigated for association in 182 Caucasian patients with IGE, but not categorised by subtype. They were compared with 178 controls in a case/control study. Further analyses were performed using a family‐based design. None of the three polymorphisms exhibited any association with IGE. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:814–816, 2000. © 2000 Wiley‐Liss, Inc.     

Neuronal nicotinic acetylcholine receptor α4 subunit (CHRNA4) and panic disorder: An association study

Anxiety disorders have been reported to be associated with low-voltage EEG (LVEEG). Some cases with LVEEG (approximately 1/3) have been linked to chromosome 20q13.2-q13.3. In the same chromosomal region, the gene for the neuronal nicotinic acetylcholine receptor α4 subunit (CHRNA4) has been located. We therefore tested the hypothesis that polymorphisms in the CHRNA4 gene show an allelic association with panic disorder. We examined the allele frequencies of three different CHRNA4 polymorphisms in patients with panic disorder and in healthy controls. No significant differences in the allele frequencies of these three polymorphisms were noted. This study does not support an association between panic disorder and the CHRNA4 gene. Am. J. Med. Genet. 74:199–201, 1997. © 1997 Wiley-Liss, Inc.     

Characterization of the genomic structure of the human neuronal nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster and identification of novel intragenic polymorphisms

Genes coding for the α5, α3, and β4 subunits (CHRNA5, CHRNA3, and CHRNB4) of the neuronal nicotinic acetylcholine receptors (nAChRs) are clustered on chromosome 15q24. Linkage of this chromosomal region to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), an idiopathic partial epilepsy, was reported in one family. Moreover, mutations in other neuronal nAChR subunit genes coding for the α4 (CHRNA4) and the β2 (CHRNB2) subunits were associated with ADNFLE. Apart from the exon-intron structure of CHRNA3, the geno-mic organization of this gene cluster was unknown, making comprehensive mutational analyses impossible. The genomic structure of CHRNA5 and CHRNB4 is here reported. Moreover, two hitherto unknown introns were identified within the 3′ untranslated region of CHRNA3, causing a partial tail-to-tail overlap with CHRNA5. Four novel intragenic polymorphisms were identified and characterized in the cluster. Received: May 11, 2001 / Accepted: August 16, 2001     

Parvalbumin-containing interneurons of the human cerebral cortex express nicotinic acetylcholine receptor proteins

Cholinergic fibers from the basal forebrain are known to contact cholinoceptive cortical pyramidal neurons. Recent electrophysiological studies have revealed that nicotinic acetylcholine receptors are also present in human cerebrocortical interneurons. A direct visualization of nicotinic receptor subunits in cortical interneurons has, however, not yet been performed. We have applied double-immunofluorescence using antibodies against parvalbumin --a marker for the Chandelier and basket cell subpopulation of interneurons--and to the alpha4 and alpha7 subunit proteins of the nicotinic acetylcholine receptor. The vast majority of the parvalbuminergic interneurons was immunoreactive for the alpha4 and the alpha7 nicotinic acetylcholine receptor. Provided these receptors would be functional--as suggested by recent electrophysiological findings--the connectivity pattern of cholinergic afferents appears much more complex than thought before. Not only direct cholinergic impact on cortical projection neurons but also the indirect modulation of these by cholinergic corticopetal fibers contacting intrinsic cortical cells would be possible.     

维生素D受体基因ApaⅠ和TaqⅠ位点多态性与帕金森病的相关性研究

目的 探讨维生素D受体(vitamin D receptor,VDR)基因ApaⅠ和Taq Ⅰ位点多态性与帕金森病(Parkinson's disease,PD)遗传易感性的相关性.方法 采用聚合酶链反应-限制性片段长度多态性技术和基因测序方法,检测285例中国北方汉族散发PD患者与285名正常对照VDR基因ApaⅠ和TaqⅠ位点多态性,并比较两组基因型和等位基因频率的差异.结果 ApaⅠ和Taq Ⅰ位点基因型和等位基因频率在PD组和对照组之间差异均无统计学意义(P＞0.05).将样本按性别及发病年龄分组后比较,ApaⅠ位点各亚组间基因型频率和等位基因频率差异亦无统计学意义(P＞0.05),而TaqⅠ位点的基因型分布在男性PD组(168例)与男性对照组(1 60名)之间差异有统计学意义(x2=4.187,P=0.032,OR=2.149,95％CI:1.011～4.567),男性PD组T等位基因频率较男性对照组显著增高(x2=3.867,P=0.036,OR=2.064,95％CI:0.989～4.307).结论 VDR基因ApaⅠ位点多态性与PD风险间无相关性,但TaqⅠ可能是男性PD的风险因素.     

Potentiation of the nicotinic acetylcholine receptor by aluminum in mammalian neurons

Aluminum (Al³⁺), a known neurotoxic substance, has long been implicated in the pathogenesis of Alzheimer’s disease and other neurodegenerative diseases. Al³⁺ targets many ligand-gated and voltage-gated ion channels and modulates their functions. In the present study, the actions of Al³⁺ on the nicotinic acetylcholine receptor (nAChR) were investigated by whole-cell patch clamp technique in acutely isolated rat trigeminal ganglion neurons. We observed that Al³⁺ potentiated nicotine-evoked inward currents in a concentration-dependent manner (10–1000 μM). The effects of Al³⁺ on nicotine-evoked currents were voltage independent. Al³⁺ appeared to increase the affinity of nicotine to nAChR but not the efficacy. Al³⁺ reduced the agonist concentration producing a half-maximal response (EC₅₀) for nicotine from 74.4±1.9 μM to 32.9±2.6 μM, but did not alter the threshold nor maximal response. On the contrary, another trivalent cation, Ga³⁺, had little effect on nicotine-evoked currents. The present results indicated that Al³⁺ enhanced the function of nAChR and this potentiation might underlie the neurological alteration induced by Al³⁺.     

Molecular analysis of sequence variants in the Fcepsilon receptor I beta gene and IL-4 gene promoter in Italian atopic families

BACKGROUND: The genetic variants in the Fcepsilon receptor I beta gene (Glu237Gly) and the T allele of the (C590T) polymorphism of interleukin (IL)-4 gene promoter were reported to be associated with atopy. But the data of the studies in different populations are contrasting with one another. METHODS: A group of 25 Italian nuclear families were studied. In each family at least two allergic subjects were present. The allergic children were 65 and the allergic relatives were 35. One hundred and three nonallergic unrelated controls included outpatiens with no history of atopy. The (C590T) promoter polymorphism of the IL-4 and the genetic variant Glu237Gly of Fcepsilon RI beta genes were analysed by the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: A significant difference was observed in the genotype frequency at codon 237 of the Fcepsilon RI beta gene between allergic children and nonatopic control (P < 0.01) and in the allergic relatives (P < 0.001). In the children, the Glu237Gly polymorphism was also associated with elevated circulating levels of immunoglobulin E. The -590C/T allele of IL-4 promoter gene showed no association with atopy. CONCLUSIONS: In our study, the Glu237Gly polymorphism of the Fcepsilon RI beta gene was associated with atopy. Our results have not pointed out an association between the (C590T) promoter polymorphism of the IL-4 gene and atopy. These data suggest the potential role of the Fc RI beta gene in the development of the allergy.     

Postnatal upregulation of alpha4 and alpha3 nicotinic receptor subunits in the brain of alpha7 nicotinic receptor-deficient mice

The nicotinic receptor subtypes are important for several physiological functions in brain and may therefore play a critical role in brain development. The alpha7 nicotinic receptors which have high Ca2+ permeability are important for cognitive, neuroprotective and trophic functions. In this study, the brain development and the expression of alpha4, alpha3, alpha7, alpha5 and beta2 nicotinic receptors were investigated in the brains of alpha7 deficient (alpha7 -/-), alpha7 heterozygous null (alpha7 +/-) and alpha7 wild-type (alpha7 +/+) mice from postnatal days (P) 7-84. The specific binding of [3H] cytisine and [3H] epibatidine, as well as the expressions of alpha4 and alpha3 nicotinic receptor subunits at mRNA and protein levels, were significantly increased in the cortex and hippocampus of alpha7 -/- and alpha7 +/- mice compared with alpha7 +/+ mice. Furthermore, the alpha4 and alpha3 nicotinic acetylcholine receptor (nAChR) subunits appeared to co-assemble with the alpha5 nAChR subunit in these above brain regions of these mice. No significant change in synaptophysin level was observed. These data suggest that increased levels of alpha4, alpha3-containing nAChRs, co-assembled with the alpha5 nAChR subunit, may contribute to the normal brain development of alpha7 -/- and alpha7 +/- mice.