B细胞活化因子(BAFF)基因rs9514828多态性与重症肌无力的关系

目的 探讨B细胞活化因子(BAFF)基因rs9514828多态性与重症肌无力(MG)的关系.方法 采用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)技术对168例MG患者和142例正常对照组进行基因分型,比较基因型和等位基因在MG患者与健康人群中及各MG亚组的分布,并观察与激素短期疗效的关系.结果 rs9514828位点的基因型及等位基因频率在MG患者及健康人群及各MG亚组中分布的差异无统计学意义(P>0.05).rs9514828位点基因型和等位基因频率与发病后1年内临床分型是否由眼肌型进展为全身型无关(P>0.05).不同激素短期疗效的MG患者rs9514828位点的基因型及等位基因频率的差异无统计学意义(P>0.05).结论 BAFF基因rs9514828位点多态性与MG疾病的易感性及激素短期疗效无显著的相关性.     

补体C3基因rs7951位点多态性与重症肌无力的相关性研究

目的 探索补体C3基因rs7951位点多态性与重症肌无力(MC)的易感性和严重程度的相关性.方法 纳入475例MG患者和487例健康对照组,采用SNPscanTM多重SNP分型技术对C3基因rs7951位点进行基因分型,比较等位基因和基因型频率在MG组及各亚组(性别、发病年龄、胸腺情况、首发受累范围以及最严重时的Osserman分型和Osterhuis评分)间的分布.结果 rs7951位点检测到CC、CT、TT3种基因型,MG组T等位基因(118/950,12.4％)高于对照组(92/974,9.4％),差异有统计学意义(P=0.036,OR=1.360,95％ CI 1.019～1.815).分别在共显性、隐性、显性和加性模型下分析MG组与对照组的基因型频率,发现基因型差异(与CC相比)在显性模型(P =0.044,OR=1.38,95％CI1.01 ～1.89)和加性模型(P=0.037,OR =1.36,95％CI 1.02 ～ 1.82)下有统计学意义.除了在15 ～50岁MG亚组与对照组之间,rs7951位点的基因型在其他各MG亚组分布频率的差异无统计学意义.结论 补体C3基因rs7951T等位基因可能与MG易感性相关.     

PTPN22基因多态性与重症肌无力的相关性

目的 探索蛋白酪氨酸磷酸酶非受体型22(protein tyrosine phosphatase, non-receptor type 22,PTPN22)基因中rs2488457和rs3811021位点的单核苷酸多态性与重症肌无力(myasthenia gravis, MG)易感性、严重程度和转型的相关性。方法 在480例MG和487例健康查体人群中，比较PTPN22基因rs2488457及rs3811021位点基因多态性在MG组及各相关亚组[性别、发病年龄、首发受累范围、胸腺情况、乙酰胆碱受体(acetylcholine receptor, AChR)抗体]、严重程度亚组、转型亚组和MG复合分类中各亚组的差异。结果 PTPN22基因rs2488457及rs3811021位点的等位基因和基因型频率在MG整组和对照组间无显著性差异，在各亚组(性别、发病年龄、伴/不伴胸腺瘤、AChR抗体阳性/阴性、首发眼肌型/全身型)与对照组间，及各亚组间无显著性差异；在严重程度亚组及转型亚组(2年内转型和未转型)与对照组及各亚组间无显著性差异。采用复合分类方法，也未发现这两个位点的等位基因和基因型与对...     

自身免疫调节因子基因多态性与重症肌无力的相关性

目的探索自身免疫调节因子AIRE基因rs3761389和rs1800520位点多态性与重症肌无力(MG)的易感性和严重程度的相关性。方法采用i MLDR技术对AIRE基因rs3761389和rs1800520位点进行基因分型,比较等位基因频率在480例MG患者(MG组)、487例健康对照者(对照组)以及MG各亚组的分布。在共显性、加性和过显性遗传模型下比较基因型频率。结果 rs3761389位点G等位基因MG组高于对照组,差异有统计学意义(P=0.035),基因型频率在加性模型下差异有统计学意义(P=0.046)。rs1800520位点MG组与对照组比较差异均无统计学意义。结论 AIRE基因rs3761389位点可能与MG的易感性相关,未发现其与MG严重程度相关;未发现rs1800520位点与MG的易感性和严重程度相关。     

TLR9基因rs352140位点多态性与重症肌无力的关系

目的探讨TLR9基因rs352140位点多态性与重症肌无力(MG)的关系。方法采用聚合酶链反应-限制性内切酶片段多态性(PCR-RFLP)方法检测MG患者TLR9基因rs352140位点的多态性,比较各基因型和等位基因在MG患者不同性别、发病年龄、胸腺瘤伴发情况、Osserman分型、最大严重程度等亚组中的分布并观察其与MG严重程度和糖皮质激素近期疗效的关系。结果 MG组和对照组间以及MG各亚组间基因型和等位基因频率无统计学差异(P0.05);糖皮质激素近期疗效差的患者中全身型比例高于眼肌型(OR=3.592,P=0.03),伴胸腺瘤者比例高于不伴胸腺瘤者(OR=4.350,P=0.016);糖皮质激素疗效差者治疗前平均定量MG评分(QMG)高于疗效好者(P=0.026);经多因素Logistic回归分析发现治疗前QMG评分越高激素疗效越差(OR=1.154,P=0.043)。结论 TLR9基因rs352140位点多态性与MG易感性无相关性,也与激素近期疗效无相关性。     

白细胞介素4受体α亚单位基因多态性与重症肌无力的相关性

目的探索IL-4R基因多态性与汉族人MG易感性和严重程度的相关性。方法采用SNPscan~(TM)技术对480例MG患者和487例健康对照的6个SNP(rs2107356、rs1805010、rs1805011、rs1805015、rs1801275和rs8832)进行分型,比较MG与对照组、MG亚组与对照组及亚组间等位基因和基因型的频率。结果 rs2107356和rs1805010的等位基因和基因型频率在伴胸腺瘤的成人亚组高于对照组和不伴胸腺瘤的成人亚组,但不伴胸腺瘤的成人亚组和对照组之间无差异。MG患者rs1801275 G等位基因的频率高于对照组,尤其是在AChR抗体阳性不伴胸腺瘤的成人亚组。rs1801275的基因型是MG患者AChR抗体阳性的独立相关因素。结论在中国汉族人群,rs2107356、rs1805010和rs1801275与MG的易感性相关。     

IL-2Rβ基因多态性与重症肌无力关联性研究

目的观察重症肌无力患者白细胞介素-2受体β亚单位(IL-2Rβ)基因rs228942、rs228941和rs743777位点多态性,探讨其与重症肌无力易感性和严重程度的关联性。方法采用SNPscanTM技术对480例重症肌无力患者和487例正常对照者IL-2Rβ基因rs228942、rs228941和rs743777位点进行基因分型,根据性别、发病年龄、抗乙酰胆碱受体(ACh R)抗体、伴与不伴胸腺瘤、发病后2年最严重临床分型和疾病最严重时Oosterhuis评分将重症肌无力患者分为不同亚组,比较重症肌无力组与对照组、重症肌无力各亚组与对照组、重症肌无力各亚组间等位基因频率,并在共显性、加性和过显性遗传模型下比较基因型频率。结果重症肌无力组IL-2Rβ基因rs228942位点T等位基因频率高于对照组(χ~2=4.692,P=0.030,OR=1.242,95%CI:1.021~1.511),基因型频率在加性遗传模型下差异有统计学意义(P=0.036,OR=1.230,95%CI:1.010~1.480)。重症肌无力组rs228942和rs228941位点组成的单倍域中GT单倍型频率高于对照组(χ~2=4.286,P=0.038),GG单倍型频率低于对照组(χ~2=5.333,P=0.021)。rs228942位点T等位基因频率在15~50岁亚组(χ~2=7.474,P=0.006,OR=1.380,95%CI:1.095~1.740)、不伴胸腺瘤亚组(χ~2=4.700,P=0.030,OR=1.261,95%CI:1.022~1.555)和发病后2年最严重全身型重症肌无力亚组(χ~2=4.715,P=0.030,OR=1.287,95%CI:1.025~1.617)均高于对照组。多因素前进法Logistic回归分析显示,发病年龄15~50岁(OR=9.026,95%CI:4.225~19.284;P=0.000)和50岁(OR=9.956,95%CI:4.475~22.149;P=0.000)、伴胸腺瘤(OR=2.578,95%CI:1.393~4.773;P=0.003)和抗ACh R抗体阳性(OR=1.946,95%CI:1.179~3.214;P=0.009)均是发病后2年最严重临床分型的独立危险因素,而基因型不是独立危险因素。结论 IL-2Rβ基因rs228942位点可能与重症肌无力易感性相关,但未发现与其严重程度相关;亦未发现rs228941和rs743777位点多态性与重症肌无力易感性和严重程度相关。     

IL-17F及IL-17A基因多态性与中国四川汉族人群多发性硬化的相关性

目的探讨中国四川汉族人群中白细胞介素(interleukin,IL)-17A多态位点rs2275913及IL-17F基因多态位点rs763780与多发性硬化(multiple sclerosis,MS)发病的相关性。方法收集川北医学院附属医院神经内科就诊的MS患者126例,以176名性别年龄相匹配的健康体检者为对照,利用聚合酶链式反应-限制性片段长度多态性方法来检测rs2275913及rs763780多态位点的等位基因及基因型频率分布,并进行统计学分析。结果 MS患者IL-17F基因rs763780位点TT基因型频率(84.92%)高于健康对照组(71.01%),差异有统计学意义(校正后P=0.036)。患者T等位基因频率(92.06%)亦高于正常人(84.66%),差异有统计学意义(校正后P=0.048)。MS患者IL-17A位点rs2275913的基因型频率及等位基因频率与健康对照者相比无统计学差异(P0.05)。结论 IL-17F基因多态位点rs763780与MS相关,TT基因型及T等位基因可能是中国四川汉族人群MS发生的危险因素。IL-17A位点rs2275913同四川汉族人MS发病无相关。     

儿茶酚胺氧甲基转移酶基因rs4680位点多态性与强迫症的关联研究

目的:探讨儿茶酚胺氧甲基转移酶(COMT)基因多态性(rs4680)与强迫症的关联性。方法:以山东汉族人群中的400例强迫症患者和459名健康对照者为研究对象,按性别、发病年龄分层,采用MassARRAY飞行时间质谱(MALDI-TOF)技术对COMT基因单核苷酸多态性(SNP)位点rs4680进行基因分型,比较各组等位基因、基因型频率。结果:COMT rs4680位点等位基因和基因型频率在强迫症组和对照组分布差异无统计学意义(P 0. 05)。按性别、发病年龄分层后,各强迫症组和对照组该位点等位基因和基因型频率分布差异也无统计学意义(P 0. 05)。结论:COMT基因多态性(rs4680)与强迫症可能不存在关联。     

CASP8基因rs6723097和rs13113位点与脑膜瘤易感性的关联研究

目的探讨中国人群CASP8基因多态性rs6723097、rs13113与脑膜瘤易感性的关系。方法采用病例对照研究方法,收集205例脑膜瘤患者和195例健康对照,运用多重SNaPshot分型技术进行多态性检测,比较基因型和等位基因在脑膜瘤组和对照组中的分布频率。分析CASP8基因rs6723097和rs13113与脑膜瘤临床表型的关联性。结果 CASP8基因rs6723097位点基因型GG、GT、TT在脑膜瘤组分布频率为23.4%、47.3%、29.3%,在对照组中为22.6%、51.3%、26.2%;rs13113位点基因型AA、AT、TT在脑膜瘤组分布频率为22.0%、49.8%、28.3%,在对照组中为24.1%、51.3%、24.6%。未见两位点多态与脑膜瘤发病风险存在关联(P>0.05)。多态性位点间的连锁不平衡检验显示rs6723097和rs13113位点呈连锁不平衡(D’=0.901)。在脑膜瘤不同临床表型之间,rs6723097和rs13113位点基因型频率分布无明显统计学差异(P>0.05)。结论在中国人群中CASP8基因rs6723097和rs13113位点遗传变异与脑膜瘤发病风险可能无关联。     

A family study of DRD3 rs6280, SLC1A2 rs3794087 and MAPT rs1052553 variants in essential tremor

Background/Objective: Despite many data suggesting a role of genetic factors in the risk for essential tremor (ET), the responsible genes have not been identified. We analyzed in ET Spanish families three single nucleotide polymorphisms (SNPs): DRD3 rs6280, SLC1A2 rs3794087, and MAPT rs1052553) previously related to an increased risk for developing the disease.

Methods: We recruited 45 subjects with ET and 13 subjects without tremor belonging to 11 families who were evaluated because of familial tremor. Diagnosis of probable or definite ET was done according to TRIG criteria. Genotyping of the 3 SNPs was done using TaqMan-based qPCR assays. Data were compared with those of healthy controls of our laboratory. Family-based association testing for disease traits was performed as well.

Results: rs6280 and rs3794087 genotype and allelic frequencies did not differ significantly between subjects with ET and healthy controls. However, rs1052553AA genotype and the allele rs1052553A allele were significantly more frequent among ET patients. rs1052553A allele was non-significantly overrepresented in ET patients compared with controls when considering only the more severely affected member of each ET family. Family-based association test for disease traits showed lack of association between ET and the three SNPs studied.

Conclusions: Our results showed a lack of association between rs6280 and rs3794087 with the risk for ET, though a marginal increased risk for ET was observed among the rs1052553A allele carriers, which was not confirmed with a family-based association study.     

Meta-analysis of polymorphism rs6311 and rs6313 in the 5-HT2AR gene and schizophrenia

Background: rs6311 and rs6313 polymorphism of 5-hydroxytryptamine 2A receptor has been widely studied regarding association with susceptibility to schizophrenia, but the results remained inconsistent.

Aims: This study aimed to assess the association between rs6311 and rs6313 polymorphism and schizophrenia using a meta-analysis.

Methods: Pubmed, Web of Science, and Embase databases were searched for all articles linking rs6311 and rs6313 polymorphism and schizophrenia. All studies which met the inclusion and exclusion criteria were included in this meta-analysis. Pooled odds ratio and 95% confidence intervals were used to evaluate the association between rs6311 and rs6313 polymorphism and schizophrenia risk. Sub-group analysis was also performed by different ethnic studies (Asian and Caucasian) and different minor allelic studies (rs6311: minor allele?=?A and minor allele?=?G; rs6313: minor allele?=?T and minor allele?=?C).

Results: Forty articles, including 50 case-control studies, were included in this meta-analysis. Specifically, 12 studies with 4100 cases and 4541 controls involved rs6311, 38 studies with 8960 cases and 9729 controls involved rs6313. The results showed that rs6311 and rs6313 were not associated with schizophrenia. Moreover, no associations were found between rs6311 and schizophrenia in different sub-groups, rs6313 was found to associated with schizophrenia among studies in which C is the minor allele.

Conclusions: This meta-analysis indicates that rs6311 and rs6313 polymorphisms of 5-HT_2AR are not associated with schizophrenia. However, the rs6313 polymorphism is associated with schizophrenia in studies in which the minor allele is C.     

Lack of association of LINGO1 rs9652490 and rs11856808 SNPs with familial essential tremor

Background: Essential tremor (ET) is a frequent movement disorder with a substantial family aggregation. A genome‐wide association study has recently shown that LINGO1 gene variants are associated with increased risk of ET. Methods: We intended to replicate these findings by genotyping rs9652490 and rs11856808 in a series of 226 familial ET subjects and 1117 healthy controls from referral movement disorder clinics in Spain. Results: We were unable to replicate the association between LINGO1 variants and familial ET. Conclusions: Our results indicate that the LINGO1 variants analyzed are not a major risk factor for developing familial ET in our population, which suggests the existence of other unknown genetic risk factors responsible for familial ET in the Spanish population.     

脂联素基因单核苷酸多态rs266729、 rs2241766、rs822396与老年缺血性 脑血管病亚型相关性研究

目的 探讨中国北方青岛地区汉族人群脂联素（adiponectin,ADIPOQ）基因多态性与老年缺血性脑血
管病发病的相关性。
方法 入组年龄大于60岁的老年缺血性脑血管病患者,按急性卒中治疗低分子肝素试验（Trial
of Org 10172 in Acute Stroke Treatment,TOAST）分型,选取大动脉粥样硬化性（large artery
atherosclerosis,LAA）和小动脉闭塞性（small artery occlusion,SAO）两种亚型患者,其中LAA 144例,
SAO 221例;402例同期查体者进行病例对照研究。对比两组的ADIPOQ基因多态性。
结果 rs266729（-11377C/G）的基因型分布在LAA组、SAO组与对照组3组中有显著差异（P =0.036）。
3组中两两比较显示,SAO组中rs266729（-11377C/G）GG基因型分布显著高于对照组（P =0.009）;在
隐性［P =0.004,比值比（odds ratio,OR）=2.478,95%可信区间（confidence interval,CI）=1.31～4.70］、
累加模式（P =0.003,OR 2.680,95%CI 1.39～5.15）下,rs266729（-11377C/G）基因型分布在SAO组与
对照组中也有显著差异,G 等位基因能增加SAO型缺血性脑血管病的风险,但在显性模式下差异无显
著性。rs822396（-3964A/G）、rs2241766（-45T/G）的基因型分布在LAA组、SAO组与对照组3组中均
无显著差异。
结论 rs266729（-11377C/G）G 等位基因与老年缺血性脑血管病发病相关,其G 等位基因变异可增
加老年患者SAO型缺血性脑血管病的风险。     

Fetuin-A基因多态性(rs4917,rs4918)与动脉粥样硬化性脑梗死的关系

目的探讨辽宁地区汉族人群胎球蛋白A(fetuin-A)基因的rs4917和rs4918多态性与动脉粥样硬化性脑梗死(atherosclerotic cerebral infarction,ACI)的相关性。方法纳入ACI患者167例作为病例组,135例同期体检的健康人作为正常对照组。通过改良多重连接酶反应技术(improved multiplex ligation detection reaction,IMLDR)检测fetuin-A基因rs4917和rs4918多态性。应用多因素Logistic回归分析研究基因多态性与ACI的相关性。结果病例组与对照组rs4917和rs4918基因型分布差异有统计学意义(P0.05);病例组患者rs4917的T等位基因频率和rs4918的G等位基因频率与对照组相比差异有统计学意义(P0.01);进一步构建显性模型和隐性模型,在隐性模型下两组差异有统计学意义(P0.01);在平衡了ACI各危险因素后,Logistic回归分析显示在隐性模型下rs4917及rs4918仍与ACI易感性相关(OR 3.039,P=0.017,95%CI 1.217~7.589)。结论 fetuin-A基因rs4917及rs4918多态性与辽宁地区汉族人群ACI易感性相关;rs4917的T/T基因型及rs4918的G/G基因型可能是辽宁地区汉族人群ACI的危险因素。     

GPX3启动子rs8177404、rs8177406、rs8177412基因多态性与脑梗死的相关性研究

目的 探讨血浆谷胱甘肽过氧化酶(Plasma Glutathione Peroxidase,GPX3)启动子rs8177404、rs8177406、m8177412位点基因多态性与脑梗死的相关性.方法 运用聚合酶链反应-连接酶检测方法(PCR-LDR)对94例脑梗死患者和80例健康对照者进行GPX3启动子基因多态性分析.结果 脑梗死组患者中rs8177404、rs8177406、rs8177412位点同时携带C等位基因高于对照组(P<0.05).经多项非条件logistic回归分析提示GPX-3启动子rs8177404、rs8177406、rs8177412同时携带C等位基因成为脑梗死的独立危险因素.结论 GPX3启动子rs8177404、rs8177406、rs8177412基因多态性与脑梗死的发生有一定的关系,可能是脑梗死的一个重要危险因素.     

rs5848 polymorphism and serum progranulin level

ObjectiveTo assess the influence of rs5848 polymorphism in serum progranulin (PGRN) level in a cohort of subjects with Alzheimer and related dementias from a tertiary referral clinic.BackgroundMutations in the GRN gene cause autosomal dominant frontotemporal dementia (FTD) with TDP-43 pathology (FTLD-TDP) through haploinsufficiency. It has recently been shown that homozygous carriers of the T allele of rs5848 have an elevated risk of developing FTD, and this polymorphism may play a role in the pathogenesis of other dementia by modifying progranulin level. We hypothesize that genotype of rs5848 may influence serum PGRN level in AD, FTD, and other dementias.MethodsBlood samples were obtained from patients with cognitive impairment and dementia referred to a tertiary dementia clinic, as well as samples from a cohort of healthy controls. Serum PGRN level was measured using an ELISA assay, and rs5848 genotype was determined by a TaqMan assay.ResultsWe found that rs5848 SNP significantly influenced serum PGRN level, with TT genotype having the lowest levels, and CC as the highest. This relationship is observed in each of the subgroups. We also confirmed that GRN mutation carriers had significantly lower serum PGRN levels than all other groups.ConclusionsThe rs5848 polymorphism significantly influences serum PGRN with TT carriers having a lower level of serum PGRN then CT and CC carriers. This is consistent with the finding that miR-659 binding to the high risk T allele of rs5848 may augment translational inhibition of GRN and alter risk of FTD and possibly other dementias.