TPM1基因相关多态性与中国北方汉族人群非综合征性唇腭裂的相关研究

目的：分析TPM1基因上游功能区3个单核苷酸多态性（single nucleotide polymorphisms, SNPs）位点与中国北方人群非综合征性唇腭裂（nonsynodromic orofacial clefts, NSOC）的关联。方法：通过对335个NSOC样本及572个健康对照样本外周血DNA的研究对目的位点行聚合酶链反应（polymerase chain reaction, PCR）扩增、DNA测序、基因分型。利用PubMed数据库（https://www.ncbi.nlm.nih.gov/pubmed）采集相关多态性位点基本信息。使用SHEsis在线软件、SPSS 20.0软件对SNPs位点的等位基因频率、基因型及单体型进行分析研究。结果：TPM1相关rs1873147、rs7179658和rs4775599完全连锁,rs1873147在唇腭裂（cleft lip and palate, CLP）组与健康对照组之间的等位基因频率差异有统计学意义（P=0.035）。结论：TPM1相关rs7179658、rs1873147和rs477559与中国北方汉族人群NSOC可...     

GCH1基因多态性与黑龙江人群非综合征性唇腭裂的关联研究

目的为了评估GCH1基因多态性在不同民族不同地区非综合征性唇腭裂中的作用,本实验研究GCH1基因在黑龙江地区与NSCL/P相关敏感性的关系。方法收集了GCH1基因研究组血样314例对照组和280例NSCLP患者作为研究对象,运用SNaPshot的方法GCH1基因的3个SNPs位点(rs17128050,rs8004018,和rs17128077)进行基因分型。对样本的等位基因和基因型频率进行分析,采用卡方检验(χ~2检验)。统计学分析全部采用SAS v9.1.3统计学软件,P<0.05认为差异有统计学意义。结果结果显示,GCH1 rs17128050(P=0.04)、GCH1 rs8004018(P=0.02)与对照组有显著性差异;CLP组GCH1 rs17128050(P=0.03)、GCH1 rs8004018(P=0.02)与对照组比较有显著性差异。结论本实验研究证明GCH1基因单核苷酸多态性与黑龙江人群非综合征性唇腭裂之间有显著相关。     

转化生长因子-α基因多态性与山东汉族人非综合征性唇腭裂的关系

目的 研究转化生长因子-α（TGF-α）基因多态性与山东汉族人非综合征性唇腭裂的关系。方法 应用多聚酶链反应（PCR）结合限制性酶切方法，对98例非综合征性唇腭裂患者与101例正常人进行TGF-α基因突变检测分析。结果 非综合征性唇腭裂患者的C2等位基因频率比正常对照组明显增高，有显著性差异（P<0.05）；有家族
史的患者，其TGF-α基因型与无家族史患者比较有显著性差异（P<0.05）。结论 TGF-α基因的突变与山东汉族人非综合征性唇腭裂的发生有相关性, 对有家族史的患者的影响可能更明显。     

非综合征性唇腭裂与同源异型盒基因1多态性的相关性研究

目的采用聚合酶链反应- 单链构象多态性（PCR- SSCP）方法研究同源异型盒基因（MSX）1外显子1的编码区，探讨非综合征性唇腭裂（NSCL/P）患者MSX1基因外显子1的编码区内是否存在基因突变。方法采用聚合酶链反应（PCR）和单链构象多态性（SSCP）方法，以45名健康人为对照组，45名NSCL/P患者作为研究对象，分析MSX1基因多态性。结果SSCP分析显示NSCL/P患者（45名）与对照组（45名）样本的电泳速率相同，提示无多态性存在。结论MSX1基因外显子1未发现多态性的存在，其与NSCL/P患者之间无明显相关性。     

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。     

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。     

THADA基因多态性与非综合征性唇腭裂的相关性研究

目的:探讨中国北方人群甲状腺腺瘤相关基因(THADA) rs7590268、rs13035011和rs6729902位点单核苷酸多态性(SNPs)与非综合征性唇腭裂(NSCL/P)的相关性。方法:应用聚合酶链式反应-连接酶检测反应(PCR-LDR)检测方法,在335例NSCL/P患者和525例健康体检者中,对THADA基因的rs7590268、rs13035011和rs6729902位点进行检测。结果:rs7590268和rs6729902多态性位点等位基因频率在唇裂组与对照组间的分布差异有统计学意义(P＜0.05),rs13035011位点基因型及等位基因频率在病例组和对照组间的分布差异无统计学意义。结论:THADA基因的rs7590268和rs6729902位点单核苷酸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。     

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.     

汉族人转化生长因子-α基因多态性与环境因素和非综合征性唇腭裂的关系

目的研究汉族人转化生长因子- α（TGF- α）基因多态性与环境因素和非综合征性唇腭裂（NSCL/P）的关系。方法通过问卷调查获得所有研究对象母亲孕早期感染史、孕期服药史及叶酸补充等资料。应用多聚酶链反应（PCR）结合限制性酶切方法，确定199例NSCL/P患者与203例正常人的基因型。将基因型与孕早期感染史、孕期服药史及叶酸补充因素进行分析。结果NSCL/P患者的C2等位基因频率比正常对照组明显增高，其差异有统计学意义（P<0.05）。孕早期感染、孕期服药及不补充叶酸的孕妇发生NSCL/P增多。C1C2基因型与孕早期感染、孕期服药和叶酸补充3个因素有交互作用。结论TGF- α基因的突变与汉族人NSCL/P的发生有相关性，孕早期感染史、孕期服药史及叶酸补充等环境因素与NSCL/P的发生有关。含有C2等位基因的个体对孕早期感染、孕期服药和叶酸缺乏3个危险因素更为敏感。     

非综合征性唇腭裂候选基因的研究进展

非综合征性唇腭裂是人类常见的先天性畸形之一,分为非综合征性唇裂或伴腭裂和单纯性腭裂,是一种多基因多因素遗传性疾病,常见的非综合征性唇腭裂相关性候选基因有干扰素调节因子6、亚甲基四氢叶酸还原酶、转化生长因子、肌节同源盒基因1和视黄酸受体仅等。本文就最常见的候选基因位点与非综合征性唇腭亵关系的研究进展作一综述。     

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.     

宁夏地区非综合征型唇腭裂环境因素的研究

目的 探讨宁夏地区非综合征型唇腭裂（NSCL/P）发病相关环境因素。方法 采用病例对照研究方法纳入NSCL/P患者453例,正常新生儿452例。对研究对象进行问卷调查,利用SPSS 16.0统计软件对数据进行卡方检验和Logistic回归分析。结果 NSCL/P患病类型构成比为唇裂︰唇裂合并腭裂︰腭裂=1︰2.02︰1.51。Logistic回归分析显示妊娠期发生异常、妊娠期感染、流产史、孕前孕中服用药物、饮茶、吸烟、饮酒、居住地附近工厂为危险因素（P<0.05）。单胎、早孕反应、食用豆制品食物、水果为保护因素（P<0.05）。结论 加强母亲孕期饮食均衡,避免感染、流产、服用药物以及不良生活习惯对降低NSCL/P的发生具有重要意义。     

No evidence for a role of CRISPLD2 in non-syndromic cleft lip with or without cleft palate in an Italian population

Non-syndromic cleft lip with or without cleft palate (NSCLP) is a malformation with variable phenotypes, resulting from a mixture of genetic and environmental factors. Some studies have supported a role for the 16q24 region and its candidate gene, CRISPLD2, in clefting. A replication study is necessary to confirm these findings. The aim of the present study was to test, by genetic linkage and association analyses, whether the candidate gene, CRISPLD2, represents a risk factor for NSCLP. The analysis of 39 multigenerational families provided formal exclusion of a linkage between NSCLP and the CRISPLD2 locus under different genetic models and non-parametric analyses. The family-based study of 239 unrelated probands and their parents revealed no association between any particular allele or haplotype and NSCLP. Therefore, the present investigation did not support the hypothesis of the involvement of CRISPLD2 in NSCLP malformation, at least with regard to the Italian population.     

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目的    研究亚甲基四氢叶酸还原酶（MTHFR）基因 C677T多态性与山东地区非综合征性唇腭裂（NSCL／P）的相关性。方法    于2008 年 9月在山东省优生技术重点实验室采用聚合酶链反应-限制性片段长度多态性（ PCR-RFLP）分析,对2006 年8月至2008年8月曾在齐鲁医院治疗的来自山东地区NSCL／P患儿家庭34户和健康查体的正常儿童家庭46户的家庭成员MTHFR基因的C677T基因型进行检测。结果    携带T等位基因的父母,其子代患NSCL／P的危险性是不携带T等位基因父母的子代的2.420倍;母子都是TT突变纯合子,子代患NSCL／P的危险性是母子为非TT纯合子的4.162倍;子代是TT突变纯合子患NSCL／P的危险性是非TT纯合子的3.812倍。结论    山东地区NSCL／P与MTHFR基因 C677T的多态性相关,与父母的基因型存在联系;T基因在母子组合的研究中有统计学意义,父母传递给子代的T等位基因对后代的患病有重要作用。     

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.     

非综合征唇裂伴或不伴腭裂对口腔健康相关生活质量的影响

目的 探讨非综合征唇裂伴或不伴腭裂对口腔健康相关生活质量的影响。方法 回顾分析2017年1月—2019年6月山东省菏泽市立医院收治的非综合征唇裂伴或不伴腭裂90例患儿的临床资料,其中唇裂不伴腭裂52例（唇裂不伴腭裂组）,唇裂伴腭裂38例（唇裂伴腭裂组）;选择同期我院口腔科常规口腔检查、口腔健康的40例儿童作为对照组,所有入组者均进行口腔健康检查。应用问卷调查法评估口腔健康对日常生活的影响,采用SPSS 22.0软件包对口腔健康与日常生活质量的相关性进行Spearman相关分析。结果 唇裂不伴腭裂组与唇裂伴腭裂组在龋失补指数（DMFT）、功能牙数目（TH）、咬合牙对、龋齿牙数、LOA≥6 mm牙数间差异具有统计学意义（P<0.05）;唇裂不伴腭裂组与唇裂伴腭裂组的DMFT、TH、咬合牙对、龋齿牙数、LOA≥6 mm牙数均显著高于对照组（P<0.05）;唇裂伴腭裂组OIDP量表各条目得分、OIDP总分显著高于唇裂不伴腭裂组（P<0.05）;唇裂不伴腭裂组OIDP量表各条目得分、OIDP总分显著高于对照组（P<0.05）。采用Spearman法分析临床口腔健康指数与OIDP分数的相关关系,唇裂不伴腭裂组与唇裂伴腭裂组DMFT、MT与根龋牙数、LOA≥6 mm牙数与OIDP分数呈负相关;咬合牙对与OIDP分数呈正相关（P<0.05）。结论 非综合征唇裂伴或不伴腭裂的口腔健康对日常生活质量均有不同程度影响。     

Non-syndromic cleft lip with or without cleft palate in Asian populations: Association analysis on three gene polymorphisms of the folate pathway

ObjectiveOrofacial clefts (OFCs) are one of the most common birth defects in humans. They are the subject of a number of investigations aimed at elucidating the bases of their complex mode of inheritance involving both genetic and environmental factors. Genes belonging to the folate pathway have been among the most studied. The aim of the investigation was to replicate previous studies reporting evidence of association between polymorphisms of folate related genes and the occurrence of non-syndromic cleft lip with or without cleft palate (NSCL/P), using three independent samples of different ancestry: from Tibet, Bangladesh and Iran, respectively.DesignSpecifically, the polymorphisms rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS, were tested.ResultsA decreased risk of NSCL/P was observed in patients presenting the C677T variant at MTHFR gene (relative risk for heterozygotes = 0.53; 95% confidence interval [C.I.] = 0.32–0.87). The investigated polymorphisms mapping at TCN2 and CBS genes did not provide any evidence of association.ConclusionOverall, these results indicate that NSCL/P risk factors differ among populations and confirm the importance of testing putative susceptibility variants in different genetic backgrounds.     

RFC1 and non-syndromic cleft lip with or without cleft palate: An association based study in Italy

The molecular basis of orofacial development is largely unknown and needs to be unravelled. Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial malformation, with an incidence of about 1/700 live births, although variable according to ethnicity. Being a multifactorial disease, it arises as a result of an interplay between genetic and environmental factors. Several approaches have been developed to identify susceptibility genes. Genes belonging to the folate/homocysteine pathway are attracting increasing interest because folate supplementation before and during early pregnancy can reduce the risk of NSCL/P. We performed a family based association study in order to assess if a genetic variant of RFC1 could be involved in NSCL/P onset.We genotyped 404 unrelated probands and their relatives for three biallelic polymorphic variants (rs1051266, rs4818789 and rs3788205), that were selected because they produced conflicting results on previous investigations.Evidence of association was found between the investigated polymorphisms and NSCL/P in our sample of the Italian population, albeit with weak significance levels.Results from this investigation provided a support of previous studies suggesting a role of RFC1 in NSCL/P aetiology, reinforcing the concept that genetic predisposition to NSCL/P varies enormously within different ethnic groups.     

Gene-gene interaction for nonsyndromic cleft lip with or without cleft palate in Chilean case-parent trios

ObjectiveNonsyndromic cleft lip with or without cleft palate (NSCL/P) is a birth defect for which several genes susceptibility genes been proposed. Consequently, it has been suggested that many of these genes belong to common inter-related pathways during craniofacial development gene-gene interaction. We evaluated the presence of gene-gene interaction for single nucleotide polymorphisms within interferon regulatory factor 6 (IRF6), muscle segment homeobox 1 (MSX1), bone morphogenetic protein 4 (BMP4) and transforming growth factor 3 (TGFB3) genes in NSCL/P risk in Chilean case-parent trios.DesignFrom previous studies, we retrieved genotypes for 13 polymorphic variants within these four genes in 152 case-parent trios. Using the trio package (R) we evaluate the gene-gen interaction in genetic markers pairs applying a 1°-of-freedom test (1df) and a confirmatory 4°-of-freedom (4df) test for epistasis followed by both a permutation test and a Benjamini-Hochberg test for multiple comparisons adjustment.ResultsWe found evidence of gene-gene interaction for rs6446693 (MSX1) and rs2268625 (TGFB3) (4df p = 0.024; permutation p = 0.015, Benjamini-Hochberg p = 0.001).ConclusionsA significant gene-gene interaction was detected for rs6446693 (MSX1) and rs2268625 (TGFB3). This finding is concordant with research in animal models showing that MSX1 and TGFB3 are expressed in common molecular pathways acting in an epistatic manner during maxillofacial development.