关键词： NASH   Nrf2   氧化应激   短发夹状RNA   慢病毒载体   HSC-T6   p66Shc   IQGAP1  

摘要： 非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)以其高发率及危害性得到了广泛关注,直到现在,其发病机制仍未完全阐明。众多研究显示遗传易感性和胰岛素抵抗可能与NASH的发生与发展关系紧密。NASH的一个很重要的危害就是其向肝纤维化发展的不可逆性,肝脏纤维化是由于细胞外基质(extracellular matrix,ECM)合成过多,同时未能及时降解导致其积聚,从而影响正常的肝脏结构和功能。ECM是由肝星状细胞(hepatic satellite cell,HSC)合成分泌的,当各种刺激诱导HSC使其活化为肌成纤维细胞,产生大量的ECM,成为肝脏纤维化的基础,HSC是研究NASH进展至关重要的靶细细。研究发现NASH患者肝组织标本肝细胞凋亡明显增多,并且随肝纤维化和肝炎炎症病变程度的增加而增加,因此,肝细胞的凋亡与NASH关系密切。核转录因子NF-E2相关因子2(NF-E2-related factor 2,Nrf2)作为细胞防御氧化应激的重要调节因子,主要是通过抵御内、外源性的氧化应激来保护细胞。Nrf2在NASH中的保护作用明确,但具体机制尚未完全阐明。p66Shc在细胞氧化应激及凋亡过程中发挥重要作用。研究显示,敲除p66Shc可增强小鼠的抗氧化能力,且延长其寿命。p66Shc在心脏、肝脏、脾脏、肺脏中表达程度不同,在动物脂肪组织中表达较高,可能与调节细胞内脂质蓄积和脂肪组织的形成有关。脂质过氧化引起的氧化应激是导致NASH纤维化的重要因素,抗氧化治疗有助于延缓肝内炎症及纤维化的发展。IQGAP1是一种Ras GTP酶活化蛋白,在细胞骨架形成和粘附中起重要作用。最新研究显示IQGAP1可能是Nrf2的伴侣分子,在保持Nrf2的稳定性过程中发挥重要作用。当上调IQGAP1表达会增加Nrf2的抗氧化效应,提高抗氧化基因的表达,下调IQGAP1的表达则可降低Nrf2的稳定性和II相酶的表达,导致抗氧化能力的减弱。目的我们在前期研究证实Nrf2在NASH的进展中起保护作用的基础上,采用慢病毒转染技术,构建上调和下调Nrf2的稳转大鼠肝星状细胞株和肝细胞株,应用葡萄糖氧化酶(Glucose oxidase,GO)构建细胞氧化应激模型,观察调控Nrf2表达对两种细胞抗氧化能力的影响,并进一步探讨调控Nrf2表达对p66Shc和IQGAP1蛋白表达的影响,为完善Nrf2在NASH中的保护机制及治疗该病提供新的研究方向。方法1.针对大鼠Nrf2基因4个干扰位点,设计并构建4种Nrf2基因sh RNA慢病毒重组质粒载体;利用PCR技术从含有rat Nrf2的质粒模板中克隆目的基因,构建含Nrf2的慢病毒表达质粒载体。进行慢病毒载体的包装、测序鉴定及滴度测定,分别转染大鼠肝星状细胞株HSC-T6和肝细胞株BRL-3A细胞,用real time PCR(RT-PCR)和Western blot技术检测转染96h后的细胞的Nrf2表达水平,确定转染成功后,用致死量浓度药物嘌呤霉素(2.5ug/ml)处理细胞,筛选并构建稳定表达的细胞株。2.将稳转的HSC-T6和BRL-3A分为对照组和氧化应激组,每个组含5个亚组,以HSC-T6为例,分别为HSC-T6(空白对照组)、HSC-T6-sh RNA-NC(下调Nrf2阴性对照组)、HSC-T6-sh RNA(下调Nrf2组)、HSC-T6-Nrf2-NC(上调Nrf2阴性对照组)和HSC-T6-Nrf2(上调Nrf2组)。对照组常规培养;氧化应激组:加入含100U/L GO的细胞培养基培养2h,制备氧化应激模型。流式细胞仪检测活性氧(Reactive oxygen species,ROS)含量,用酶标仪来检测细胞生存率及丙二醛(malondialdehyde,MDA)、乳酸脱氢酶(Lactic Acid Dehydrogenase,LDH)、超氧化物歧化酶(super-oxide dismutase,SOD)的表达水平。3.分别提取实验2中对照组和氧化应激组的细胞总蛋白,Western blot检测p66Shc和IQGAP1蛋白表达情况。结果1.测序证实Nrf2的sh RNA及表达质粒的成功构建。HSC-T6和BRL-3A转染重组慢病毒载体后常规培养96 h,RT-PCR和Western blot证实重组慢病毒载体能在m RNA和蛋白水平有效下调/上调靶细胞中Nrf2基因的表达。用致死量浓度药物嘌呤霉素处理转染细胞后,再次RT-PCR和Western blot证实Nrf2基因的表达在m RNA和蛋白水平均被抑制/促进。我们成功构建下调/上调Nrf2表达的稳定表达HSC-T6和BRL-3A细胞株。2.对于HSC-T6,对照组各指标(ROS、MDA、LDH、生存率和

关键词： IQGAP1   RhoC   宫颈鳞癌   免疫组织化学  

摘要： 目的:检测IQGAP1和RhoC在正常宫颈、宫颈癌前病变及宫颈鳞癌组织中的表达,并分析二者在宫颈鳞癌发生发展中的作用和意义。方法:采用Envision免疫组织化学方法检测IQGAP1和Rho C在13例正常宫颈组织、16例宫颈癌前病变组织(其中6例宫颈上皮内瘤变II级,10例宫颈上皮内瘤变Ⅲ级)、45例宫颈鳞癌组织中的表达。IQGAP1和RhoC在不同宫颈组织中的表达及二者的表达与宫颈鳞癌各临床病理参数之间的差异采用卡方检验,相关性分析采用Spearman相关分析。采用双侧检验,P<0.05具有统计学意义。结果:1、IQGAP1在正常宫颈、宫颈癌前病变及宫颈鳞癌组织中的表达主要定位于细胞膜,部分定位在细胞质。2、IQGAP1在正常宫颈组、宫颈癌前病变组及宫颈鳞癌组中的阳性表达率分别为23.08%(3/13)、25%(4/16)、82.22%(37/45),三组间差异具有统计学意义(X2=27.538,P<0.001)。正常宫颈组与宫颈癌前病变组比较,差异无统计学意义(X2=0.918,P=1.000>0.05);宫颈癌前病变组与宫颈鳞癌组比较,差异具有统计学意义(X2=17.153,P<0.001);正常宫颈组与宫颈鳞癌组比较,差异有统计学意义(X2=17.439,P<0.001)。3、IQGAP1在宫颈鳞癌中的表达与癌症组织分化程度、宫旁浸润、脉管浸润、淋巴结转移和间质浸润深度有关(P<0.05);而与患者年龄、临床分期及肿瘤大小无关(P>0.05)。4、RhoC在正常宫颈、宫颈癌前病变及宫颈鳞癌组织中的表达主要定位于细胞质。5、RhoC在正常宫颈组、宫颈癌前病变及宫颈鳞癌组中的阳性表达率分别为23.08%(3/13)、56.25%(9/16)和82.22%(37/45),三组间差异有统计学意义(X2=20.712,P<0.001)。正常宫颈组与宫颈癌前病变组比较,差异无统计学意义(X2=3.972,P=0.133>0.05);宫颈癌前病变组与宫颈鳞癌组比较,差异有统计学意义(X2=9.219,P=0.010<0.05);正常宫颈组与宫颈鳞癌组比较,差异具有统计学意义(X2=14.819,P<0.001)。6、RhoC在宫颈鳞癌中的表达与患者年龄、癌症组织分化程度和淋巴结转移有关(P<0.05);而与患者临床分期、宫旁浸润、脉管浸润、间质浸润深度和肿瘤大小无关(P>0.05)。7、在宫颈鳞癌组织中,IQGAP1和Rho C的表达具有相关性(rs=0.392,P=0.008),即具有正相关关系。结论:1、IQGAP1及Rho C在正常宫颈组织、宫颈癌前病变组织及宫颈鳞癌组织中的阳性表达均呈依次升高趋势,提示IQGAP1和Rho C可能参与了宫颈鳞癌的发生发展。2、IQGAP1在宫颈鳞癌有淋巴结转移组、有脉管浸润组、深肌层浸润组、有宫旁浸润组及肿瘤低分化组中的阳性表达分别强于无淋巴结转移组、无脉管浸润组、浅肌层浸润组、无宫旁浸润组及肿瘤高-中分化组;但与患者年龄、临床分期及肿瘤大小无关。3、RhoC在宫颈鳞癌高年龄组、肿瘤低分化组及有淋巴结转移组中的阳性表达分别强于低年龄组、无淋巴结转移组及肿瘤高-中分化组;但与患者临床分期、间质浸润、宫旁浸润、脉管浸润及肿瘤大小无关。4、在宫颈鳞癌组织中,IQGAP1和Rho C的表达可能有正相关关系。

关键词： 血管新生   肺炎衣原体   衣原体属   IQGAP1   信号通路  

摘要： 目的:观察肺炎衣原体***感染对血管新生的影响,探讨IQGAP1信号通路在***感染促进血管新生中的作用及其可能机制。方法及结果:微管腔形成实验和细胞迁移实验结果显示,***感染促进血管新生的作用与其增强血管内皮细胞(VEC)的迁移能力有关。随后,我们发现,***感染可能通过促使IQGAP1酪氨酸和丝氨酸磷酸化而诱导血管新生。免疫共

关键词： 子宫内膜样腺癌   肿瘤组织   IQGAP1蛋白   PCNA蛋白   表达水平   病理分期   淋巴结转移   临床诊断  

摘要： 目的：研究IQGAP1和PCNA在子宫内膜样腺癌中的表达及意义，探讨其表达在子宫内膜样腺癌中的诊断、手术-病理分期、病理分级、淋巴结转移、肌层浸润深度及临床中的相关意义。　　方法：收集30例正常子宫内膜、25例子宫内膜不典型增生组织及35例子宫内膜样腺癌组织，应用SP法(免疫组织化学链霉抗生物素蛋白-过氧化物酶连接法)分别检测IQGAP1和PCNA在其中的表达情况，然后依次分析其与子宫内膜样腺癌患者在手术-病理分期、术后病理分级、有无淋巴结转移、肌层浸润等诸多因素之间的关系，同时研究两者在子宫内膜样腺癌组织表达的相关性。　　结果：IQGAP1和PCNA在正常子宫内膜的表达低于子宫内膜样腺癌以及不典型增生子宫内膜里面的表达，其差异水平具备统计学意义(P＜0.05)，IQGAP1和PCNA在正常子宫内膜和子宫内膜不典型增生里面的表达差异同样具备统计学意义(P＜0.05)，而子宫内膜样腺癌中IQGAP1和PCNA的表达在病理学分级、手术-病理分期、癌组织浸润深度＞=1/2组与＜1/2组、淋巴结转移组与无淋巴结转移组，都具备显著差异(P＜0.05)。IQGAP1与PCNA的阳性表达率会在临床分期加重以及肌层浸润深度拓展的情况下有所提升，而有淋巴结转移组也要高于无淋巴结转移组。IQGAP1和PCNA在子宫内膜样腺癌中的表达呈正相关。　　结论：IQGAP1和PCNA在子宫内膜样腺癌组织中呈现高表达，其原因应该是受到肿瘤发生与发展的影响，可为诊断子宫内膜样腺癌恶性程度及转移情况提供了依据。在子宫内膜样腺癌中IQGAP1和PCNA的表达呈正相关，认为在子宫内膜样腺癌的发展、侵袭、转移中IQGAP1和PCNA之间有关联性。将IQGAP1和PCNA作为两种有研究价值的子宫内膜样腺癌的肿瘤标记物，对临床上辅助诊断及预测子宫内膜样腺癌有一定的意义。

关键词： 乳腺癌   基底细胞样型   免疫组化   IQGAP1   Rac1   Cdc42  

摘要： 目的:检测IQGAP1蛋白、Rac1蛋白和Cdc42蛋白在基底细胞样型乳腺癌(basal-like breast carcinoma,BLBC)、非基底细胞样型乳腺癌(non-basal-like breast carcinoma,NON-BLBC)及癌旁正常乳腺组织中的表达情况,分析IQGAP1蛋白、Rac1蛋白和Cdc42蛋白与基底细胞样型乳腺癌的肿瘤大小、组织学分级、淋巴结转移及p TNM分期等临床病理特征之间的关系及IQGAP1蛋白、Rac1蛋白和Cdc42蛋白三者之间在基底细胞样型乳腺癌中表达的相关性,探讨IQGAP1、Rac1和Cdc42在肿瘤发生、发展及侵袭转移中的作用,为基底细胞样型乳腺癌转移机制研究及临床的靶向治疗,进一步提供理论依据。方法:通过免疫组化技术检测IQGAP1蛋白、Rac1蛋白和Cdc42蛋白分别在60例基底细胞样乳腺癌、45例非基底细胞样乳腺癌、35例正常乳腺组织中的表达情况。免疫组化结果采用统计软件SPSS17.0进行统计分析,IQGAP1蛋白、Rac1蛋白和Cdc42蛋白基底细胞样型乳腺癌、非基底细胞样型乳腺癌及癌旁正常乳腺组织三组表达的差异,及IQGAP1蛋白、Rac1蛋白和Cdc42蛋白与基底细胞样型乳腺癌临床病理特征之间关系的比较采用c2检验及Fisher确切概率法,检验水准α=0.05,P<0.05;IQGAP1蛋白、Rac1蛋白和Cdc42蛋白三者之间相关性分析采用Spearman相关分析,检验水准α=0.05,P<0.05,差异有统计学意义;基底细胞样型乳腺癌、非基底细胞样型乳腺癌及癌旁正常乳腺组织三组间的两两比较采用c2分割法,检验水准α=0.0125,P<0.0125,差异有统计学意义。结果:IQGAP1在BLBC、NON-BLBC及正常乳腺组织中的表达率分别为85.00%(51/60)、82.22%(37/45)、28.57%(10/35),差异有统计学意义(P<0.05);IQGAP1在BLBC中的表达高于正常乳腺组织,差异有统计学意义(P<0.0125),IQGAP1在NON-BLBC中的表达与高于正常乳腺组织,差异有统计学意义(P<0.0125);IQGAP1在BLBC中的表达与肿瘤直径、p TNM密切相关,差异有统计学意义(P<0.05)。Rac1在BLBC、NON-BLBC及正常乳腺组织中的表达率分别为81.67%(49/60)、51.11%(23/45)、20.00%(7/35),差异有统计学意义(P<0.05);Rac1在BLBC中的表达高于NON-BLBC,差异有统计学意义(P<0.0125),Rac1在BLBC中的表达高于正常乳腺组织,差异有统计学意义(P<0.0125),Rac1在NON-BLBC中的表达高于与正常乳腺组织,差异有统计学意义(P<0.0125);Rac1在BLBC中的表达与肿瘤组织学分级、淋巴结转移及p TNM密切相关,差异有统计学意义(P<0.05)。Cdc42在BLBC、NON-BLBC及正常乳腺组织中的表达率分别为85.00%(51/60)、55.55%(25/45)、31.42%(11/35),差异有统计学意义(P<0.05);Cdc42在BLBC中的表达高于NON-BLBC,差异有统计学意义(P<0.0125),Cdc42在BLBC中的表达高于正常乳腺组织,差异有统计学意义(P<0.0125),;Cdc42在BLBC中的表达与淋巴结转移、p TNM密切相关,差异有统计学意义(P<0.05)。在BLBC中,IQGAP1与Rac1的表达呈正相关(r=0.404,P<0.05),IQGAP1与Cdc42的表达呈正相关(r=0.608,P<0.001),Rac1与Cdc42的表达呈正相关(r=0.645,P<0.001)。结论:IQGAP1、Rac1和Cdc42在BLBC均呈现高表达,且与BLBC的肿瘤直径、淋巴结转移及p TNM等临床病理特点密切相关,提示三者可能是促进BLBC肿瘤的局部侵袭和远处转移的重要因素,在BLBC的发生发展中起着关键性的作用,提示三者今后可作为BLBC预后不良的指标及治疗的靶点;IQGAP1、Rac1和Cdc42在BLBC的表达均呈正相关关系,提示三者协同参与了BLBC中肿瘤细胞转化与侵袭的过程,共同促进BLBC的发生发展及远处转移,提示联合检测IQGAP1蛋白、Rac1蛋白和Cdc42蛋白的表达对判断BLBC转移潜能和预后具有指导意义。

关键词： Cytoplasm   Non-small cell lung cancer   Nuclear membrane   Cyclins   Metastasis   Adenocarcinoma   Squamous cell carcinoma   Prognosis  

摘要： Background: IQ-domain GTPase-activating protein 1 (IQGAP1) binds to Dishevelled (Dvl) and functions as a modulator of Dvl nuclear localization in Xenopus embryos. However, the relationship between IQGAP1 and Dvl in tumor tissues is unclear. Materials and Methods: We used immunohistochemistry to assess the expressions of IQGAP1 and Dvl in a cohort of 111 non-small cell lung cancer (NSCLC) patients. Association of their localization expressions with clinicopathological factors was also analyzed. Results: The positive rate of IQGAP1 in primary tumors was 48.6% (54/111) for its cytoplamic expression, 9.0% (10/111) for nuclear expression and 31.5% (35/111) for membranous expression;the positive rate of Dvl was 65.8% (73/111) for cytoplamic expression, 9.9% (11/111) for nuclear expression and 10.8% (12/111) for membranous expression. Coexpression rate of IQGAP1 and Dvl was 77.8% (42/54) in the cytoplasm, 80.0% (8/10) in the nucleus and 8.6% (3/35) in the membrane. Coexpression of IQGAP1 and Dvl in the cytoplasm and nucleus were significantly correlated (P<0.05), but not in the membrane (P>0.05). The positive expression rates of cyclin D1 and c-myc were significantly higher in the group of IQGAP1 and Dvl coexpression in the nucleus than that in the cytoplasm. Coexpression rate of IQGAP1 and Dvl in the cytoplasm and nucleus was significantly higher in lymph nodal metastases (63.3%, 19/30) than in primary growths (38.3%, 31/81), correlating with poor prognosis. Five-year survival time after resection in the group with their coexpression in the cytoplasm and nucleus was significantly lower than that with no coexpression (44.705+/-3.355 vs 58.403+/-2.543 months, p<0.05). Conclusions: Coexpression of IQGAP1 and Dvl in the cytoplasm and nucleus was correlated with the lymph nodal metastase and poor prognosis of NSCLC, and coexpression in nucleus might play a critical role in the activation of canonical Wnt pathway.

关键词： ILK   Cell growth   IQGAP1   ERK1/2   NK-kappa B  

摘要： Background: Increased activity or expression of integrin-linked kinase (ILK), which regulates cell adhesion, migration, and proliferation, leads to oncogenesis. We identified the molecular basis for the regulation of ILK and its alternative role in conferring ERK1/2/NF-kappa B-mediated growth advantages to gastric cancer cells. Results: Inhibiting ILK with short hairpin RNA or T315, a putative ILK inhibitor, abolished NF-kappa B-mediated the growth in the human gastric cancer cells AGS, SNU-1, MKN45, and GES-1. ILK stimulated Ras activity to activate the c-Raf/MEK1/2/ ERK1/2/ribosomal S6 kinase/inhibitor of kappa Ba/NF-kappa B signaling by facilitating the formation of the IQ motif-containing GTPase-activating protein 1 (IQGAP1)-Ras complex. Forced enzymatic ILK expression promoted cell growth by facilitating ERK1/2/NF-kappa B signaling. PI3K activation or decreased PTEN expression prolonged ERK1/2 activation by protecting ILK from proteasome-mediated degradation. C-terminus of heat shock cognate 70 interacting protein, an HSP90-associated E3 ubiquitin ligase, mediated ILK ubiquitination to control PI3K- and HSP90-regulated ILK stabilization and signaling. In addition to cell growth, the identified pathway promoted cell migration and reduced the sensitivity of gastric cancer cells to the anticancer agents 5-fluorouracil and cisplatin. Additionally, exogenous administration of EGF as well as overexpression of EGFR triggered ILK- and IQGAP1-regulated ERK1/2/NF-kappa B activation, cell growth, and migration. Conclusion: An increase in ILK non-canonically promotes ERK1/2/NF-kappa B activation and leads to the growth of gastric cancer cells.

摘要： The intracellular scaffold protein IQGAP1 supports protein complexes in conjunction with numerous binding partners involved in multiple cellular professes. Here, we determined that IQGAP1 modulates airway smooth muscle contractility. Compared with WT controls, at baseline as well as after immune sensitization and challenge, Iqgap1(-/-) mice had higher airway responsiveness. Tracheal rings from Iqgap1(-/-) mice generated greater agonist-induced contractile force, even after removal of the epithelium. RhoA, a regulator of airway smooth muscle contractility, was activated in airway smooth muscle lysates from Iqgap1(-/-) mice. Likewise, knockdown of IQGAP1 in primary human airway smooth muscle cells increased RhoA activity. Immunoprecipitation studies indicated that IQGAP1 binds to both RhoA and p190A-RhoGAP, a GTPase-activating protein that normally inhibits RhoA activation. Proximity ligation assays in primary airway human smooth muscle cells and mouse tracheal sections revealed colocalization of p190A-RhoGAP and RhoA;however, these proteins did not colocalize in IQGAP1 knockdown cells or in Iqgap1(-/-) trachea. Compared with healthy controls, human subjects with asthma had decreased IQGAP1 expression in airway biopsies. Together, these data demonstrate that IQGAP1 acts as a scaffold that colocalizes p190A-RhoGAP and RhoA, inactivating RhoA and suppressing airway smooth muscle contraction. Furthermore, our results suggest that IQGAP1 has the potential to modulate airway contraction severity in acute asthma.

关键词： 肿瘤   支架蛋白IQGAP1   侵袭   综述文献  

摘要： 目的总结支架蛋白IQGAP1与肿瘤的研究进展,探讨其在恶性肿瘤迁移、侵袭和增殖方面的作用。方法应用PubMed和CNKI期刊全文数据库检索系统,以"支架蛋白1和肿瘤"为关键词,检索2000-01-2013-07相关文献,纳入标准:1)支架蛋白IQGAP1的特性和功能;2)支架蛋白IQGAP1在肿瘤组织中的表达;3)针对IQGAP1为靶点的肿瘤细胞相关实验研究。根据纳入标准,符合分析的文献35篇。结果 IQGAP1作为一种细胞骨架蛋白,在肿瘤细胞的运动和增殖等方面的作用引起越来越多的重视。首先IQGAP1可激活Rac1/CDC42信号通路,促使细胞形成侵袭性伪足;与肌动蛋白形成多聚体,引导细胞定向运动;减少正常细胞连接的E-cadherin复合体形成,降低细胞间的黏附力;加速细胞外基质(extracellular cell matrix,ECM)降解增强肿瘤细胞的侵袭能力。同时,IQGAP1还可激活MAPK/Raf/MEK/ERK信号传导通路,与β-catenin结合控制Wnt通路,后两者是促进细胞增殖的重要通路;与VEGF形成复合体,提高血管内皮细胞的运动和增殖能力,促进肿瘤血管的增生。IQGAP1在结肠癌、乳腺癌、肺癌、前列腺癌和卵巢癌等组织中表达明显增高,并与肿瘤复发、远处转移和患者生存时间密切相关;IQGAP1胞膜分布预示肿瘤的复发与分化,在侵袭性强、分化低的肿瘤IQGAP1更多分布于细胞外周;其通过改变上皮细胞的极性参与幽门螺杆菌导致胃肠道肿瘤的发病机制。结论支架蛋白IQGAP1在肿瘤细胞的运动、侵袭和增殖等生物学行为中发挥重要功能,在肿瘤组织中的表达和定位与肿瘤复发、转移和预后判断密切相关。IQGAP1在肿瘤的基础和临床研究中具有广阔的前景。

关键词： MicroRNAs   Single nucleotide polymorphisms   Haplotypes   Memory recall   Homozygosity   Human genomics   Learning and memory   Protein expression  

摘要： As a product of the unique evolution of the human brain, human cognitive performance is largely a collection of heritable traits. Rather surprisingly, to date there have been no reported cases to highlight genes that underwent adaptive evolution in humans and which carry polymorphisms that have a marked effect on cognitive performance. IQ motif containing GTPase activating protein 1 (IQGAP1), a scaffold protein, affects learning and memory in a dose-dependent manner. Its expression is regulated by miR-124 through the binding sites in the 3'UTR, where a SNP (rs1042538) exists in the core-binding motif. Here we showed that this SNP can influence the miR-target interaction both in vitro and in vivo. Individuals carrying the derived T alleles have higher IQGAP1 expression in the brain as compared to the ancestral A allele carriers. We observed a significant and male-specific association between rs1042538 and tactile performances in two independent cohorts. Males with the derived allele displayed higher tactual performances as compared to those with the ancestral allele. Furthermore, we found a highly diverged allele-frequency distribution of rs1042538 among world human populations, likely caused by natural selection and/or recent population expansion. These results suggest that current human populations still carry sequence variations that affect cognitive performances and that these genetic variants may likely have been subject to comparatively recent natural selection.