MTR基因rs1805087位点多态性与非综合征性唇腭裂的关联性研究

目的:研究蛋氨酸合成酶(methionine synthase,MTR/MS)基因rs1805087位点单核苷酸多态性与山西人群非综合征性唇腭裂(NSCL/P)的相关性。方法:采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法对135个NSCL/P核心家庭、150例正常新生儿及其母亲的MTR基因rs1805087位点多态性进行检测;用人群关联研究、病例组核心家庭的传递不平衡检验(TDT)和单体型的相对危险度(HHRR)进行统计分析。结果:本研究中GG基因型较少,故将AG和GG基因型合并后与AA基因型比较。病例组子代及母亲和对照组之间,基因型分布和等位基因频率比较,差异均无统计学意义(P>0.05);唇裂组和唇腭裂组子代及母亲基因型分布和等位基因频率,与对照组差异均无统计学意义(P>0.05);病例组核心家庭分析,TDT检验χ2=0.083,P>0.05,HHRR分析χ2=0.112,P>0.05,说明携带有突变基因G并不能增加NSCL/P的发病风险。结论:本研究结果未显示MTR基因rs1805087位点多态性与山西人群非综合征性唇腭裂之间存在相关性。     

肌节同源盒-1基因A448T多态性与山西部分人群非综合征性唇腭裂发病的相关性

目的 探讨肌节同源盒(msx)-1基因A448T的多态性与山西部分人群非综合征性唇腭裂(NSCL/P)发病间的关系.方法 以聚合酶链反应-限制性片段长度多态性方法行msx-1基因A448T的多态性检测,并行其遗传统计分析.结果 msx-1等位基因频率在对照组和NSCL/P组之间的差异有显著性统计学意义(P＜0.01),对照组T位点频率明显高于NSCL/P组(对照组0.55,NSCL/P组0.26).结论 msx-1/A448T(rs13127820)基因的多态性与山西部分人群NSCL/P发病可能相关,此位点的T等位基因在NSCL/P的发生中可能起保护效应.     

山西人群MTHFR基因rs1801133位点多态性与非综合征性唇腭裂的关联性研究

目的:研究亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)基因rs1801133位点多态性与非综合征性唇腭裂(NSCL/P)的关系。方法:采用聚合酶链反应-限制性片段长度多态性方法,检测334例非综合征性唇腭裂患者和314例正常对照组的MTHFR基因rs1801133位点的多态性。结果:MTHFR基因rs1801133位点基因型频率分布符合Hardy-Weinberg平衡;MTHFR基因rs1801133位点基因型及等位基因的分布在NSCL/P组与对照组之间均无统计学意义(P>0.05)。结论:MTHFR基因rs1801133位点多态性与山西人群非综合征性唇腭裂的发生无关。     

亚甲基四氢叶酸还原酶C677T多态性与非综合征性唇腭裂的关系

目的研究亚甲基四氢叶酸还原酶基因C677T多态性与非综合征性唇腭裂的关系。方法利用聚合酶链反应-限制性片段长度多态性方法（PCR-RFLP）,在168例非综合征性唇腭裂患者和192名正常对照中,对MTHFR基因C677T单核苷酸多态性（SNP,rs1801133）进行检测。利用拟合优度卡方检验,分析基因型分布频率是否符合Hardy-Weinberg平衡定律;应用UNPHASED软件包分析多态性位点与非综合征性唇腭裂的相关性。结果MTHFRC677T多态性基因型频率分布符合Hardy-Weinberg平衡;MTHFR C677T等位基因分布在NSCL／P组与对照组之间有显著性差异（P〈0.05）,正常组中T等位基因的频率明显高于NSCL／P组。结论MTHFR C677T多态性位点在中国人群中与非综合征性唇腭裂形成的发生相关联。     

叶酸代谢相关基因与非综合征性唇腭裂的关系

目的：研究叶酸代谢相关基因在中国华北人群中与非综合征性唇腭裂的关系。方法：利用聚合酶链反应-限制性片段长度多态性方法,在115例非综合征性唇腭裂患者和192名正常对照个体中,对CBS和SHMT1基因2个单核苷酸多态性（SNP）rs397589和rs1979276进行检测。利用拟合优度卡方检验,分析基因型分布频率是否符合Hardy-Weinberg平衡定律;应用UNPHASED软件包分析单个基因多态性位点以及基因-基因相互作用与非综合征性唇腭裂的相关性。结果：2个基因上的SNP位点基因型频率分布均符合Hardy-Weinberg平衡;等位基因分布在NSCL/P组与对照组之间无显著性差异;rs397589TT和rs1979276TT基因型能增加NSCL/P患病风险（OR=2.60,95%CI=0.43-15.87;OR=1.62,95%CI=0.22-11.70）;携带rs397589GT-rs1979276CT个体在患者中的频率高于对照组（χ2=4.780,P=0.029）。结论：CBS和SHMT1基因相互作用可能参与非综合征性唇腭裂的发生。     

MSX1基因多态性与山西地区非综合征性唇腭裂的相关性研究

目的:研究MSX1基因外显子区rs13127820(M146L)、rs62636562(A274V)位点多态性与非综合征性唇腭裂(non-syn-dromic cleft lip with or without cleft palate,NSCL/P)的关系。方法:通过聚合酶链反应-限制性片段长度多态性方法,检测243例非综合征性唇腭裂(NSCL/P)患者和292例正常对照者全血标本中MSX1基因rs13127820(M146L)、rs62636562(A274V)位点的多态性。结果:MSX1基因位点rs13127820(M146L)、rs62636562(A274V)基因型频率分布符合Hardy-Weinberg平衡;MSX1基因位点rs13127820(M146L)、rs62636562(A274V)等位基因频率分布在NSCL/P组与对照组之间差异有统计学意义(P<0.05)。结论:结果显示MSX1基因位点多态性与NSCL/P的发生有关。     

叶酸代谢相关基因多态性与山西地区非综合征性唇腭裂的相关性研究

目的:研究叶酸代谢相关基因MTHFR基因rsl801133、MTHFD1基因rs2236225位点多态性与非综合征性唇腭裂(NSCL/P)的关系。方法:通过聚合酶链反应-限制性片段长度多态性方法,检测265例NSCL/P患者和276例正常对照者的MTHFR基因rsl801133、MTHFD1基因rs2236225位点的多态性。结果:MTHFR基因rsl801133位点、MTHFD1基因rs2236225位点的基因型频率分布符合Hardy-Weinberg平衡;MTHFR基因rsl801133位点、MTHFD1基因rs2236225位点的等位基因频率分布在NSCL/P组与对照组之间差异无统计学意义(P>0.05)。结论:MTHFR基因rsl801133位点、MTHFD1基因rs2236225位点的多态性与NSCL/P的发生无关。     

染色体10q25位点多态性与中国非综合征性唇腭裂的关联研究

目的:研究染色体10q25上2个单核苷酸多态性(single nucleotide polymorphisms,SNP)位点rs7078160、rs4752028与中国人群非综合征性唇腭裂(non-syndromic cleft lip with or without cleft palate,NSCL/P)发病的相关性。方法:收集180例NSCL/P患者作为病例组,并按照表型分为单纯唇裂组、唇腭裂组、单纯腭裂组,将单纯唇裂组和单纯腭裂组合并为唇/腭裂组;选取360名健康人作为对照组。采集病例组和对照组的外周血血样并提取DNA。对上述2个SNP设计引物,PCR扩增其序列,通过二代测序进行基因型分型。利用SPSS19.0软件包中的χ2检验对病例组与对照组的基因型以及等位基因频率进行分析。结果:rs7078160的等位基因频率在唇/腭裂组与对照组中的差异最为显著(P=0.008,OR=1.500,95%CI=1.116~2.016),rs4752028位点的等位基因频率在唇/腭裂组和对照组间亦存在显著差异(P=0.028,OR=1.424,95%CI=1.041~1.948)。结论:染色体10q25区域的rs7078160和rs4752028位点与中国人群非综合征性唇腭裂的发病相关。     

DHFR基因rs11742688位点单核苷酸多态性与中国东北人群唇腭裂相关性研究

目的：探讨二氢叶酸还原酶（DHFR）基因 rs11742688位点单核苷酸多态性与中国东北部人群的非综合征唇腭裂（NSCL／P）的相关性。方法：采用聚合酶链－限制性片段长度多态性方法检测东北地区220例 NSCL／P 及其父母（其中包括138例完整的核心家系）,180例正常儿童作为对照组,进行 HW 平衡检验,用 SPSS 统计学软件对病例组和对照组进行检验及计算 OR 值和95％可信区间。结果：病例对照研究结果显示,东北地区单纯唇裂和唇腭裂 rs11742688位点的 TT 基因型频率差异无显著性（χ2＝0．439,P ＞0．05）。结论：DHFR rs11742688位点 T 等位基因与东北人群的 NSCL／P 无相关性。     

宁夏回汉族人群中FOXE1基因多态性与非综合征型唇腭裂的相关性研究

目的:探讨宁夏回汉人群FOXE1基因rs3758249、rs10217225和rs4460498位点单核苷酸多态性与非综合征型唇腭裂发病的相关性。方法:收集宁夏地区回、汉族非综合征型唇腭裂患者207例,其中回族69例,汉族138例;正常对照组292例,其中,回族72例,汉族220例。采用PCR-RFLP方法检测FOXE1基因rs3758249、rs10217225和rs4460498多态位点的基因型,进行病例对照分析。结果:在回汉人群中,与正常对照组比较,单纯唇裂组和唇腭裂组rs3758249、rs10217225和rs4460498多态位点基因型和等位基因频率存在统计学差异(P0.05);而在单纯腭裂组差异无显著性(P0.05)。分别对汉族和回族人群内病例对照分析,发现唇裂并唇腭裂组rs3758249、rs10217225和rs4460498多态位点基因型在汉族和回族人群中的均存在差异性(P0.05)。病例组内进行回、汉族基因型比较,发现rs10217225多态性在宁夏地区回、汉患者中存在差异性(P0.05),而rs3758249、rs4460498差异没有显著性。结论:在宁夏回汉族人群中,FOXE1基因的rs3758249、rs10217225和rs4460498位点单核苷酸多态性与非综合征型唇腭裂存在相关性;回汉族人群间基因型没有统计学差异。     

VAX1 gene associated non-syndromic cleft lip with or without palate in Western Han Chinese

ObjectiveNon-syndromic cleft lip with or without palate (NSCL/P) is one of the most common human birth defects, it results from multiple genetic and environmental risk factors. Recently, GWA studies identified associations between NSCL/P and two genetic risk loci, rs7078160 and rs4752028, at VAX1.DesignCurrently, we tried to investigate the roles of the two loci among 302 NSCL/P trios (129 non-syndromic cleft lip only (NSCLO) trios and 173 non-syndromic cleft lip and cleft palate (NSCLP) trios) from Western Han Chinese. The two SNPs were genotyped by SNPscan method; Hardy–Weinberg equilibrium test, allelic TDT and parent-of-origin effect were performed by PLINK software, and genotypic TDT and haplotype by FBAT software.ResultsAllelic TDT analysis revealed allele A at rs7078160 was over-transmitted among NSCL/P group (P = 0.0086, OR_transmission = 1.36, 95%CI: 1.08–1.72). Parent-of-origin effect analysis revealed a paternal special over-transmission of allele A at rs708260 in NSCL/P group (P = 0.0079). Haplotype AC of rs7078160-rs4752028 was significant over-transmitted in the NSCL/P group.ConclusionsOur study firstly confirmed that allele A at rs7078160 at VAX1 gene was a risk factor for NSCL/P in Western Han Chinese population.     

中国北方人群非综合征性唇腭裂与BMP4基因多态性的关系

目的探讨BMP4基因rs17563多态性与中国北方人群非综合征性唇腭裂的相关性。方法使用聚合酶链反应-限制性内切酶片段长度多态性分析(PCR-RFLP)方法,在116例非综合征性唇腭裂患者和123名健康对照中,对BMP4基因单核苷酸多态性进行检测。利用SPSS13.0软件分析BMP4基因多态性与非综合征性唇腭裂的相关性。结果 BMP4基因型频率分布符合Hardy-Weinberg平衡。在非综合征性唇腭裂组中CC纯合子明显高于健康对照组,差异有统计学意义(P<0.001)。结论 BMP4基因rs17563多态性可能与中国北方人群非综合征性唇腭裂的发生相关。     

宁夏回汉族人群Wnt3基因单核苷酸多态性与非综合征型唇腭裂相关性的研究

目的 探讨宁夏回汉族人群中Wnt3基因rs142167和rs7216231位点单核苷酸多态性（SNP）与非综合征型唇腭裂（NSCL/P）的相关性。方法 收集宁夏地区回汉族人群非综合征型唇腭裂患者371例为病例组,其中汉族患者166例,回族患者205例;收集患者父亲196例,患者母亲224例,其中150例患者为NSCL/P核心家系;258例健康新生儿为对照组,其中汉族190例,回族68例。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测Wnt3基因多态位点rs142167和rs7216231基因型,对比分析2组的基因型和等位基因,并进行传递不平衡检验（TDT）和以家系为基础的相关性检验（FBAT）分析。结果 回汉族人群病例组与对照组比较及其民族分层比较,唇裂、腭裂、唇腭裂及总病例组rs142167和rs7216231位点均无统计学差异（P＞0.05）。TDT分析结果显示：rs142167和rs7216231位点的等位基因均不存在过传递（P＞0.05）。FBAT分析结果显示：单倍型G-G具有统计学意义（P<0.05）。结论 Wnt3基因多态性与宁夏地区回汉族人群非综合征型唇腭裂不存在相关性。     

Association between BMP4 gene polymorphisms and cleft lip with or without cleft palate in a population from South China

ObjectivePrevious studies have suggested an association between several polymorphisms of the BMP4 gene and susceptibility to non-syndromic cleft lip with or without cleft palate (NSCL/P) in various populations. However, this association may vary according to ethnic group and the form of NSCL/P. This study analyzed the association between the BMP4 gene polymorphisms rs762642, rs17563, and rs10130587 with the risk of cleft lip only (CLO), cleft palate only (CPO), and cleft lip with palate (CLP) in a population from South China.MethodsThis case-control study included 165 patients with NSCL/P (53 patients with CPO, 52 with CLO, and 60 with CLP) and 52 healthy volunteers. Peripheral blood samples were collected from all subjects to genotype the rs762642, rs17563, and rs10130587 polymorphisms by direct sequencing. Genotype and allelic frequencies of these polymorphisms were compared between healthy volunteers and patients with various forms of NSCL/P.ResultsThe genotype and allelic frequencies of rs762642 differed significantly between subgroups (CPO and CLP) and normal controls, whereas a significant difference was observed only in the CLO subgroup for the rs17563 polymorphism and in the CLO and CLP groups for the rs10130587 polymorphism. In addition, we identified a novel association of a BMP4 gene polymorphism, which was in linkage disequilibrium with the rs10130587 polymorphism, with CLO and CLP.ConclusionThe BMP4 gene polymorphisms rs762642, rs17563, and rs10130587 exhibit different associations with different forms of NSCL/P, suggesting that different forms of NSCL/P may have different etiologies.     

TCN2基因与非综合征性唇腭裂的关系

目的研究叶酸代谢相关基因TCN2与中国人群中非综合征性唇腭裂的关系。方法通过聚合酶链反应-限制性片段长度多态性,在108例非综合征性唇腭裂患者和184名正常对照个体中,对TCN2基因2个单核苷酸多态性（SNP）（rs10418和rs1801198）进行检测。利用拟合优度卡方检验,分析基因型分布频率是否符合Hardy-Weinberg平衡定律;应用UNPHASED软件包分析单个单核苷酸多态性位点以及两个位点单倍型与非综合征性唇腭裂的相关性。结果 2个SNP位点基因型频率分布均符合Hardy-Weinberg平衡;等位基因分布和单倍型组合在非综合征性唇腭裂患者与对照组之间无显著性差异;rs10418 TT基因型能增加非综合征性唇腭裂患病风险。结论 TCN2基因rs10418 TT基因型是非综合征性唇腭裂的危险因素。     

MTHFR基因单核苷酸多态性与新疆地区维吾尔族非综合征性唇腭裂的相关性研究

目的:探讨MTHFR基因rs1801133、rs3818762、rs1801131、rs1476413、rs1994798位点单核苷酸多态性与新疆地区维吾尔人群非综合征型唇腭裂的相关性。方法:研究对象均为新疆地区世居维吾尔族,病例组非综合征性唇腭裂患者100例,对照组为60例因上呼吸道感染而住院的儿童,用DNA二代测序技术对目标区域进行测序,进行遗传学分析。结果:在新疆维吾尔人群中,与对照组相比,NSCL/P组rs1801133、rs3818762、rs1801131、rs1476413、rs1994798位点基因型及等位基因频率分布差异无统计学意义。连锁不平衡分析显示:以上5个位点位于同一个单倍体域,rs3818762和rs1476413等2个位点存在较强的连锁不平衡(r²=0.938,D’=1)。单倍型分析可推测出最常见的单倍体型共5种:GCTAA>GCTAG>CTGGG>GCTGG>GCGGG,5种单倍体型在病例组与对照组间分布差别无统计学意义。结论:MTHFR基因rs1801133、rs3818762、rs1801131、rs1476413、rs1994798等5个位点基因型及等位基因频率在患儿与正常人之间比较没有统计学意义。     

Homozygote C/C at rs12543318 was risk factor for non‐syndromic cleft lip only from Western Han Chinese population

Non‐syndromic cleft lip with or without cleft palate (NSCL/P) is a complex disorder, and it results from both of the genetic modifiers and environmental factors, with genetic modifiers contributes to it more than environmental factors. GWASs made great progress in identifying the candidate genes for NSCL/P, but the findings need to be replicated in other populations. In this study, we selected eleven SNPs from recent GWASs and GWAS meta‐analysis to investigate their associations among 308 NSCL/P trios (134 non‐syndromic cleft lip only (NSCLO) trios and 174 non‐syndromic cleft lip with cleft palate (NSCLP) trios) from Han Chinese population. All SNPs were genotyped using SNPscan method and analyzed the data with FBAT, PLINK, and R package. Allelic TDT analysis showed that allele A at rs12543318 was associated with NSCLO trios (P = .0032, OR = 0.57, 95% CI: 0.39‐0.83), and parent‐of‐origin effect analysis indicated that allele A at rs12543318 was significantly maternally undertransmitted among NSCLO (P = .0046), which implied the potential influence of genomic imprinting; global TDT further confirmed this association. Individual genotypic TDT showed homozygote C/C at rs12543318 was overtransmitted among NSCLO (Z = 3.79, P = .00015) and NSCL/P groups (Z = 3.83, P = .00013), which indicated that it could increase the risk to have cleft babies. Our findings indicated that rs12543318 was associated with NSCLO from Western Han Chinese population, which will give new scientific evidence for later researches in the etiology of NSOCs.