IRF6基因rs642961位点多态性与非综合征性唇裂伴或不伴腭裂的相关性研究

目的探讨中国北方人群干扰素调节因子6(IRF6)基因rs642961位点多态性与非综合征性唇裂伴或不伴腭裂(NSCL±P)的相关性。方法收集中国北方人群88个病例核心家庭和116个正常儿童作对照,用四引物扩增受阻突变体系聚合酶链反应(tetra-primer ARMS-PCR)的方法,进行IRF6基因rs642961检测;用人群关联研究、传递不平衡检验(TDT)、单倍型相对风险率(HHRR)、家庭为基础的关联检验(family-based association test,FBAT)等进行统计分析。结果子代、父亲、母亲三个亚组人群的IRF6基因rs642961位点的基因型在NSCL±P组与对照组的分布差异具有统计学意义(P<0.05),OR值及其95%可信区间均不包含1,提示IRF6基因rs642961位点的变异能增加NSCL±P发病的危险。核心家庭资料TDT和HHRR的结果均显示有统计学差异(P<0.05),FBAT分析提示可能存在加性传递模式(P<0.05),进一步支持IRF6基因rs642961位点的突变和NSCL±P发生相关。结论在中国北方人群中,IRF6基因rs642961位点多态性与NSCL±P发病相关。     

MTHFR基因多态性与非综合征性唇腭裂的遗传易感性

目的　探讨 MTHFR基因热敏感性多态性在非综合征性唇腭裂 (NSCL / P)发病以及遗传易感性中的作用。方法　应用聚合酶链反应 -限制性片段长度多态性 (PCR- RFL P)方法检测 MTH-FR热敏感性基因型 ;对 2 9个 NSCL / P核心家庭进行以父母为对照的病例对照研究 ,计算 TDT和HHRR;另外对该 2 9例 NSCL / P患儿及其父母和 5 8例正常儿童及其父母进行了成组病例对照研究 ,分别计算 MTHFR热敏感性纯合突变对 NSCL / P的比值比。结果　核心家庭分析显示 TDT(χ2 ) =3.5 6 ,P >0 .0 5 ,HHRR(成组χ2 ) =1.6 9,P >0 .0 5 ;患儿及其母亲、父亲 MTHFR热敏感性纯合突变对 NSCL / P的相对危险度 OR值分别为 0 .72、1.11和 0 .75 ,P >0 .0 5。结论　 MTHFR基因热敏感性多态性可能不是 NSCL / P的遗传易感性因素     

黔北人群MTHFR基因A1298C位点多态性与非综合征性唇腭裂的相关性研究

目的探讨黔北人群MTHFR基因A1298C位点的多态性及其与非综合征性唇腭裂的相关性。方法采用PCR和测序方法对45个对照组和60个NSCL/P病例组核心家系MTHFR基因A1298C位点进行扩增和测序;对样本群体进行Hardy-Weinberg遗传检测,对两组人群进行基因型频率、等位基因频率比较及OR分析;对病例组进行HHRR和TDT检验。结果对照组和病例组均符合Hardy-Weinberg平衡法则(P0.05);对照组与病例组子代和父亲的A1298C位点基因型和等位基因频率分布差异均无统计学意义(P0.05),而两组的母亲A1298C位点基因型及等位基因频率分布有统计学差异(P0.05),母亲携带C突变等位基因可能有利于降低子代罹患唇腭裂的风险;病例组双亲与子代的基因型和等位基因频率差异均无统计学意义(P0.05);MTHFR基因A1298C多态性与非综合征性唇腭裂无显著相关性(P0.05)。结论 MTHFR基因A1298C位点多态性可能与黔北地区人群区非综合征性唇腭裂的发生没有相关性。     

神经管畸形儿及其父母还原叶酸载体基因多态性的 FBAT关联研究

目的：探讨神经管畸形（neural tube defects, NTDs）儿及其父母的还原叶酸载体基因（reduced folate carrier gene, RFC1）A80G多态性在NTDs发生危险中的作用,为探讨NTDs遗传易感标记物提供流行病学依据。方法：应用聚合酶链反应-限制性片段长度多态性（PCR?鄄RFLP）技术,检测104例NTDs儿及其父母和100例健康对照儿及其父母的RFC1 A80G多态性,利用病例-父母对照研究中传递/不平衡检验（TDT检验）和以家系为基础的关联检验（FBAT检验）分析NTDs儿的父母RFC1基因A80G多态性与NTDs发生危险的关联,及其在子代中传递的作用强度。结果：患儿父母均为杂合子GA/GA的比例高达36.36%,NTDs患儿成为纯合子GG的概率为25%时具有统计学意义（P＜0.05）,表明患儿接受父母遗传的G等位基因的概率均为25%,并有发生NTDs危险的可能。NTDs的TDT检验结果显示,患儿父母传递等位基因G的危险性是传递等位基因A危险性的1.56 倍（95%CI：1.07~2.28）,认为该基因在亲代和NTDs子代间存在传递失衡现象。FBAT检验中,不论显性模型还是隐性模型,均未发现等位基因G与NTDs的发生危险存在关联,该结果与上述病例-父母对照研究TDT检验结果不一致。结论：虽然TDT检验中G等位基因与NTDs发生危险有关,但FBAT检验未发现G等位基因与NTDs发生危险存在关联,应进一步加大核心家系数量验证该结果。     

还原叶酸载体基因多态性与先天性心脏病和唇腭裂关联的研究

目的 检验还原叶酸载体基因(RFC1)A80G多态性与先天性心脏病(CHD)和唇腭裂之间的关联,为寻找CHD和唇腭裂危险因素的遗传易感标志物提供流行病学依据。方法 采用RFLP-PCR方法,对67个CHD患儿家庭、82个唇腭裂患儿家庭和100个正常儿童家庭成员的外周血DNA进行RFC1第80位SNP检测,利用核心家庭标本进行以家庭为基础的关联检验(FBAT),并分析了子代RFC1基因型与母亲孕期前后增补叶酸的相互作用。结果 不增补叶酸的母亲生育CHD儿的危险高于增补叶酸的母亲(OR=2 68,95％CI:1 14-6 41),即母亲孕期未增补叶酸与CHD发生危险的关联有统计学意义(x2=6.213,P=0 013);在FBAT检验中,RFC1 G等位基因与CHD发病危险有统计学关联(Z=2 140,P<0 05),表明RFC1 G等位基因可能是CHD发病的遗传易感基因,未发现唇腭裂与RFC1之间的统计学关联。结论 RFC1 G等位基因可能是CHD发生的遗传易感基因之一,子代RFC1基因GG或GA基因型、母亲孕期叶酸缺乏可能增加CHD的发病危险。     

干扰素调节因子-6基因多态性与非综合征性唇腭裂易感性的Meta分析

目的评价干扰素调节因子-6(IRF-6)基因G820A多态性与非综合征性唇腭裂(NSCL/P)易感性的关系。方法计算机检索中国学术期刊数据库、中国生物医学文献数据库、万方学术期刊数据库、PubMed、Medline及Science Direct等,选择IRF-6基因G820A多态性与NSCL/P易感性有关的病例对照研究。采用Rev Man5.3软件进行统计分析。结果共纳入研究15项包括7470例研究对象。Meta分析结果显示,在亚洲和美洲人群中,携带G等位基因的个体罹患NSCL/P的风险均高于携带A等位基因的个体(G vs.A:OR=1.53,95%CI 1.40～1.68;GG vs.GA:OR=1.67,95%CI 1.47～1.90;GG vs.AA:OR=2.02,95%CI 1.64～2.49;GG vs.GA+AA:OR=1.74,95%CI 1.54～1.96;GG+GA vs.AA:OR=1.61,95%CI 1.33～1.96),差异均具有统计学意义。结论 IRF-6基因G820A多态性是亚洲和美洲人群发生非综合征性唇腭裂的危险因素。     

还原叶酸载体基因多态性与神经管畸形关联的父母-病例对照研究

目的对神经管畸形（NTDs）发病危险和还原叶酸载体基因（RFC1）A80G多态性进行关联研究，为寻找NTDs的遗传易感标志物提供流行病学依据。方法采用RFLP—PCR方法．对104例NTDs儿及其父母和99名正常儿童及其父母的外周血DNA进行RFC1第80位SNP检测，对核心家庭基因型进行病例对照研究，对NTDs杂合子父母G等位基因进行传递不平衡检验（TOT）。结果NTDs儿G等位基因频率高于对照儿，OR值为1．64（95％CI：1．08～2．49）；GG基因型的患儿发生NTDs危险高于AA基因型（OR=2．56，95％CI：1．04～6．36）；TDT结果显示，RFC1等位基因G与NTDs之间存在关联（x^2=5．2364，P〈0．05），携带G等位基因发生NTDs的危险是非携带者的1．56倍（95％CI：1．07～2．28）。结论发现在中国人群中RFC1基因多态性与NTDs存在关联，初步表明该基因G等位基因可能是NTDs发生的遗传易感基因之一。     

TGFA基因多态性与NSCL/P的遗传易感性

目的:探讨中国汉族人TGFA基因的多态性对非综合征性唇腭裂的遗传易感性的作用。方法:76例核心家庭和60例正常对照儿童的TGFA基因型,采用病例对照研究和传递不平衡检验进行分析。结果:病例对照研究结果表示:(2χ=7.77,P<0.05),TDT(2χ=5.26,P<0.05))。结论:TGFA C2等位基因在NSCL/P中存在连锁不平衡,TGFA基因多态性可能是中国汉族人NSCL/P的遗传易感性因素。     

转化生长因子α基因多态性和父亲吸烟的交互作用与唇腭裂发生的关联研究

目的探讨中国部分地区人群非综合征型唇裂伴或不伴腭裂（nsCL／P）与转化生长因子α基因（TGFα）TaqI位点多态性之间的关系,及其与父亲吸烟之间的交互作用。方法采用PCR-RFLP方法,对170个nsCL／P核心家庭成员DNA标本进行TGFα TaqI突变位点的基因型检测。利用TDT检验分析该突变与nsCL／P发生之间的关系,采用TDT检验的logistic回归模型分析TGFα基因突变与父亲吸烟之间的交互作用。结果未发现TGFα TaqI突变的致病C2等位基因在nsCL／P核心家庭成员中存在传递不平衡,但是父亲吸烟的nsCL／P核心家庭中C2C1基因型的父母将致病的C2等位基因传递给子代的频率是父亲不吸烟的nsCL／P核心家庭父母的约1／5（0．062～0．711）,控制其他环境因素后发现,父亲是否吸烟与TGFα TaqI突变位点C2等位基因传递之间是偏离乘法模型的负交互作用OR=0．102（0．017～0．619）。结论父亲是否吸烟与中国部分地区人群TGFα基因突变存在交互作用,但还有待于进一步研究加以验证。     

HMGB1基因多态性与豫北地区肺结核易感性的相关性

目的探讨高迁移率族蛋白1(HMGB1)单核苷酸多态性与豫北地区肺结核患者易感性的相关性。方法选取2017年1—12月新乡医学院第一附属医院被确诊为肺结核的320例患者为结核组,该院同时期300名健康体检者为对照组。采用PCR技术和Sanger测序对结核组和对照组的HMGB1 rs1412125(-1615A/G)、rs1045411(+1177G/A)、rs2249825(+3814C/G)位点进行基因分型,通过对两组等位基因频率、基因型频率及四种遗传模型(共显性、显性、隐性和超显性)分析,研究HMGB1基因多态性与肺结核的易感性。结果所有位点的基因型分布均符合Hardy-Weinberg平衡。两组间+1177G/A位点等位基因频率差异具有统计学意义(OR=1.485,95%CI:1.110～1.986,P=0.007),其基因型分布差异也具有统计学意义(P0.05);+1177G/A位点的共显性模型中,与GG基因型相比,AG基因型(OR=1.447,95%CI:1.025～2.041,P=0.035)和AA基因型(OR=2.812,95%CI:0.985～8.033,P=0.045)与肺结核的易感性相关;+1177G/A位点的显性模型[(AG+AA)vs GG,OR=1.524,95%CI:1.090～2.131,P=0.014]也与肺结核的易感性相关;在+1177G/A位点的隐性模型和超显性模型中,两组间差异无统计学意义(P0.05)。在-1615A/G和+3814C/G位点两组间等位基因及基因型分布差异均无统计学意(P0.05)。结论 HMGB1基因rs1045411(+1177G/A)位点多态性可能与肺结核的易感性相关,其等位基因A可能是肺结核的易感基因,携带rs1045411(+1177G/A)A等位基因可能增加患肺结核的风险。     

Genetic variation of infant reduced folate carrier (A80G) and risk of orofacial defects and congenital heart defects in China

PURPOSE: This study was designed to investigate whether the risks of congenital heart defects (CHD) and orofacial defects were influenced by a polymorphism of the offspring's RFC1 or by an interaction between the RFC1 gene and maternal periconceptional use of folic acid. METHODS: A case-control study was conducted. A total of 82 families with a child affected by cleft lip with or without cleft palate (CLP), 67 families with a child-affected by CHD, and 100 nonmalformed control families were genotyped using PCR-RFLP. RFC1 G allele was tested through family-based association test. RESULTS: Among mothers who did not use folic acid, the risks of 4.03 (95% CI = 1.33-12.77) for the G80/G80 genotype and 4.14 (95% CI = 1.06-16.82) for the G80/A80 genotype were observed relative to the A80/A80 genotype for CHD offspring. In family-based association tests (FBAT), offspring carrying the G allele for RFC1 is at increased risk for CHD (Z = 2.140, p < .05). No significant association was found between either RFC1 genotype or maternal folic acid supplementation and the risks of CLP. CONCLUSIONS: Our findings suggest that the RFC1 G allele is likely to be an important candidate gene in folate transport and to be associated with risk for CHD. This study found modest evidence for a gene-nutrient interaction between offspring RFC1 genotype and periconceptional intake of folic acid on the risk of congenital heart defects.     

Familial aggregation of serum total cholesterol: a population-based family study in eastern Finland

BACKGROUND: The Finnish population has a high risk of coronary heart disease, which is associated to a high population level of serum total cholesterol (CHOL) already evident at early ages. The study investigated the familial aggregation of CHOL in a sample of families with young offspring from eastern Finland. METHODS: Fifteen-year-old offspring were examined during 1996-1997 and their biological parents were examined during 1993-1994. A total of 224 children were invited and 184 families participated, of which 123 were included in the analysis with complete data. The main outcome measure was the CHOL (millimoles per liter). RESULTS: Significant positive familial correlations of CHOL were found for the pairs of mother/offspring (r = 0.35, P < 0.001, n = 111), father/offspring (r = 0.29, P = 0.007, n = 82), mother/daughter (r = 0.46, P = 0.001, n = 49), mother/son (r = 0.27, P = 0.036, n = 62), and father/daughter (r = 0.35, P = 0.035, n = 36). The adjustments for the offspring's gender and body mass index (BMI) and the parent's age, BMI, education, and family history of acute myocardial infarction did not alter these results. There was a higher proportion of the offspring in the highest quartile of CHOL when the mother had CHOL > or =5 mmol/L (OR = 3.26, 95% CI = 1.2-8.9, n = 111). CONCLUSIONS: The study confirmed the familial aggregation of CHOL. The consistent CHOL association between the mother and the offspring may indicate the key role of the mother for the primary prevention of hypercholesterolemia.     

新疆维、汉两民族非综合征性唇腭裂IRF6基因多态性分析

目的:探讨非综合征性唇腭裂(NSCL/P)干扰素调节因子6(IRF6)rs2013162位点单核苷酸多态性(SNP)在新疆维、汉两民族内和民族间基因型和等位基因型的频率差异。方法:抽取100例NSCL/P患者作为NSCL/P组(维吾尔族50例、汉族50例),对照组100例(维吾尔族50例、汉族50例),运用聚合酶链式反应-限制性片段长度多态性(PCR-RELF)技术来分析IRF6基因的多态性,病例-对照研究分析两组基因型和等位基因型频率及两民族内和民族间频率的差异。结果:rs2013162位点GG基因型和等位基因G和T频率在NSCL/P组和对照组中分布差异有统计学意义(P<0.05),维、汉两民族内rs2013162位点维吾尔族中GG和TT基因型及等位基因G和T分布差异有统计学意义(P<0.05),维、汉两民族间rs2013162位点NSCL/P组中维吾尔族GG和TT基因型和等位基因G的频率均高于汉族,两民族间基因型和等位基因型分布差异均无统计学意义(P>0.05)。结论:新疆维、汉族NSCL/P与rs2013162位点GG基因型及等位基因G存在相关性。     

RF6基因多态性与黔北人群非综合征性唇腭裂的相关性研究

目的 探讨黔北地区人群IRF6基因rs2235371和rs2235373 SNP位点的多态性及其与非综合征性唇腭裂的相关性。方法 采用PCR和测序方法对153个对照儿童和123个NSCL/P儿童的IRF6基因中2个SNP位点rs2235371和rs2235373进行扩增和测序;对样本群体进行Hardy-Weinberg平衡分析,比较2组人群的基因型频率、等位基因频率及OR分析;两位点连锁不平衡分析。结果 对照组与病例组人群rs2235371基因型均含有GG、GA和AA型,rs2235373位点均含有CC、CT和TT型。对于2个位点,对照组和病例组均符合Hardy-Weinberg平衡法则(P＞0.05)。2组人群中,rs2235371和rs2235373位点的等位基因和基因型差异均有统计学意义(P＜0.05);rs2235371位点GGvsGA的OR值(95%CI) =1.725(1.025～2.902),GGvsAA的OR值(95%CI) = 2.100(1.109～4.328);rs2235373位点CCvsTT的OR值(95%CI) = 2.263(1.348～5.015),CTvsTT的OR值(95%CI) = 2.061(1.108～2.169);(P＜0.05)。rs2235371和rs2235373位点存在连锁不平衡,GC单倍型是主要的单倍体型,对NSCL/P均有致病风险,OR值(95%CI)= 1.722(1.219～2.431), (P＜0.05)。结论 在黔北地区人群中,IRF6基因 rs2235371和rs2235373位点均具有多态性;rs2235371位点的GG基因型和rs2235373位点的CC、CT基因型与NSCL/P的发生有相关性;rs2235371和rs2235373位点存在连锁不平衡,GC单倍型对NSCL/P有致病风险。     

父母超重肥胖与儿童代谢指标异常聚集性的关系

目的 探讨父母超重肥胖与儿童代谢指标异常聚集性的关系,为心血管病危险因素的防控提供科学依据。方法 2017年11月-2018年1月采用方便整群抽样的方法,以山东省淄博市桓台县某所小学作为调查点,将身体测量、问卷调查和血生化检测均完整的1 280名6~11岁儿童作为研究对象。分析父母超重肥胖与儿童代谢指标异常及其聚集性的关系。结果 父母一方和双方均超重肥胖的检出率分别为55.6%和19.8%。儿童代谢指标异常(腹型肥胖、血压偏高)及其聚集性(2项和≥3项代谢指标异常)检出率在父母不同体重状态组间差异有统计学意义(P<0.05或<0.001)。与父母均体重正常的儿童相比,父母一方超重肥胖儿童存在腹型肥胖(OR＝2.00)和1项代谢指标异常(OR＝1.47)的危险性较高(P<0.05或<0.001),而双方均超重肥胖儿童存在腹型肥胖(OR＝3.08)、血压偏高(OR＝1.74)和代谢异常指标聚集(OR＝1.64~4.60)的危险性更高(P<0.05或<0.001)。结论 父母超重肥胖与儿童腹型肥胖、血压偏高和代谢指标异常聚集性存在关联。这提示应该对有父母超重肥胖史的高危儿童进行重点干预。     

上海市10~17岁青少年超重肥胖检出率及相关因素研究

【目的】 调查上海市10~17岁青少年超重及肥胖检出率及分布情况,分析相关影响因素。 【方法】 用国家“十一五”支撑代谢综合征项目样本中上海市横向部分7 737名青少年体格评估数据,分别采用中国(WGOC)及国际(IOTF)青少年超重肥胖标准计算超重肥胖检出率,比较两标准差异,并分析超重肥胖的影响因素。 【结果】 上海市10~17岁青少年超重、肥胖检出率分别为:11.9%、6.2%,总超重率18.1%(WGOC标准);13.6%、3.6%,总超重率17.2%(IOTF标准)。按WGOC标准,男女生超重、肥胖检出率分别为男:17.5%、7.7%; 女6.0%、4.6%。单因素中性别、年龄、出生体重、家庭收入、父母生育年龄、父母吸烟史、父母超重史、母饮酒史、父亲学历、父系高血压/糖尿病/高血脂/冠心病/脂肪肝史及母系脂肪肝史等17项是青少年超重的影响因素,多因素分析:性别(OR＝3.376,P＜0.001)、年龄(OR＝1.736,P＜0.001)、家庭收入(OR＝1.467,P＝0.001,)、母生育年龄(OR＝0.704,P＝0.023)、父超重(OR＝1.545,P＜0.001)、母超重(OR＝3.14,P＜0.001)、父系高血脂史(OR＝1.293,P＝0.018)是青少年超重的影响因素。 【结论】 上海市有近1/5的青少年超重肥胖,居国内较高水平。性别、年龄、家族史等是青少年超重肥胖的主要危险因素。     

Moderation and Mediation in the Relationship Between Mothers'' or Fathers'' Serious Psychological Distress and Adolescent Substance Use: Findings from a National Sample

PURPOSE: This study estimated percentages of adolescents living with a mother or father with serious psychological distress (SPD), and examined moderation and mediation of the relationships between mother or father SPD and adolescent substance use. METHODS: We analyzed data from nationally representative samples of adolescents interviewed with their mothers (n = 4734) and fathers (n = 3176) in the combined 2002 and 2003 National Surveys on Drug Use and Health (NSDUHs). RESULTS: An estimated 4.1% of adolescents living with their father had a father with SPD during the past year, and 11.5% of adolescents living with their mother had a mother with SPD during this time period. A positive association was found between mothers' SPD and adolescent binge drinking (OR = 1.49, 95% CI = 1.01-2.21), but no association was found between fathers' SPD and adolescent binge drinking. Mothers' SPD was associated with increased risk of binge drinking among adolescents aged 14-15 years (OR = 2.52, 95% CI = 1.38-4.60), and fathers' SPD was associated with lowered risk of binge drinking among black adolescents (OR = .08, 95% CI = .01-.79). A positive association was found between mothers' SPD and adolescent illicit drug use (OR = 1.55, 95% CI = 1.08-2.23), but no association was found between fathers' SPD and adolescent illicit drug use. Mothers' SPD was associated with increased risk of illicit drug use among female adolescents (OR = 2.14, 95% CI = 1.24-3.70) and among adolescents of white ethnicity (OR = 1.78, 95% CI = 1.19, 2.68). Parental involvement partially mediated the relationship between mothers' SPD and daughters' illicit drug use; mothers' SPD was associated with lower levels of parental involvement, which in turn were associated with an increased probability of daughters' illicit drug use. CONCLUSIONS: Overall, parents' SPD is associated differentially with adolescent substance use depending on the gender of parent and adolescent, adolescent age, race/ethnicity, and substance used. Parental involvement appears to be one mechanism through which mothers' SPD influences daughters' illicit drug use. Future research should further consider the interindividual effects of parents' SPD and associated parenting behaviors on adolescent risk behaviors.