93例儿童血脂谱水平与ApoB基因多态性关系的研究

目的观察儿童血脂谱水平与载脂蛋白Ｂ（ＡｐｏＢ）基因变异的关系。方法对９３名８～１１岁汉族儿童进行了ＡｐｏＢ基因ＸｂａⅠ位点多态性基因型频率及基因型与血脂谱水平关系的研究。结果此人群中ＸｂａⅠ位点优势等位基因Ｘ－频率为０．９６７，少见等位基因Ｘ＋频率为０．０３３；Ｘ－Ｘ＋基因型者（此人群中无Ｘ＋Ｘ＋者）血浆总胆固醇、低密度脂蛋白－胆固醇（ＬＤＬ－ｃｈ）水平均值（４．５９和２．９８ｍｍｏｌ／Ｌ）显著高于Ｘ－Ｘ－基因型者（３．８４和２．３２ｍｍｏｌ／Ｌ），全部６例Ｘ－Ｘ＋者中的４例，其总胆固醇和／或ＬＤＬ－ｃｈ测定值分别超过了Ｐ９０，显示了Ｘ＋等位基因与高血浆胆固醇水平的联系。结论ＡｐｏＢ基因ＸｂａⅠ位点多态性与儿童血脂谱水平有一定程度的关联，有可能是儿童血脂谱水平异常的遗传标志之一。     

Apolipoprotein A-I positively associated with diabetes in women independently of apolipoprotein E genotype and apolipoprotein B levels

ObjectiveGiven the elevated apolipoprotein (apo) A-I level enhancement of type 2 diabetes among Turks, the interrelation among it, apoB, and apoE genotype with respect to the likelihood of diabetes and metabolic syndrome (MetS), and the role of gender need further investigation.MethodsA random sample of Turkish adults genotyped for apoE with measured serum apoB and apoA-I concentrations was studied cross-sectionally. Apo ?2/?4 genotype was excluded to avoid confounding. MetS was identified by modified criteria of the Adult Treatment Panel III.ResultsAmong 1673 participants, ?3 homozygotes prevailed in 74%, apoE2 (?2/?3, ?2/?2) in 12%, and apoE4 (?3/?4, ?4/?4) in 13%. Low-density lipoprotein cholesterol and apoB levels were significantly lower and apoE concentrations higher in the apoE2 than in the remaining groups. ApoA-I levels in female subjects were significantly higher than in the E4 group. Multivariable analysis for determinants of apoB showed apoE genotype, serum apoE, C-reactive protein, apoA-I, and triacylglycerol levels to be major independent covariates. Logistic regression analyses for MetS, adjusted for potential confounders, revealed that apoB is linked to MetS in men independently of serum triacylglycerols and apoE2 group, whereas that in women in the apoE2 group was associated with MetS by mediation by triacylglycerols or apoB. The independent inverse association of apoA-I with MetS was considered apparent. Multi-adjusted likelihood of diabetes was associated only with triacylglycerol levels and, in women, with apoA-I (odds ratio 1.43, 95% confidence interval 1.10–1.86, per 1 SD increment).ConclusionThe confirmed positive association of serum apoA-I with diabetes in Turkish women is independent of apoE genotype and apoB levels.     

学龄儿童载脂蛋白CⅢ基因变异与血脂谱的关系研究

为了解载脂蛋白CⅢ基因多态性与学龄儿童血脂谱变异的关系 ,对 30 8名在校儿童 (7～ 11岁 )进行血脂水平测定及载脂蛋白CⅢ基因SacⅠ位点多态性检测 (PCR RFLP方法 )。结果表明载脂蛋白CⅢ基因SacⅠ位点杂合突变型 (+ - )检出率为 48 7% ,纯合突变型 (+ +)检出率为 7 5 % ,其等位基因 (+)频率为31 8% ,高于上海 (12 % )及白种人 (6 % ) ,与日本人 (34 % )接近 ,提示遗传变异有人群及种族差异 ;不同基因型儿童血脂水平比较显示 ,纯合突变基因型儿童的TG水平高于野生型 (P <0 0 5 ) ;高甘油三酯组 (+ +)基因型频率为 30 0 % ,高于对照组 6 7% (P <0 0 5 ) ;ApoCⅢ SacⅠ位点 (+)等位基因可使TG水平升高0 0 31mmol L。结果提示 ,载脂蛋白CⅢ基因SacⅠ位点突变与儿童甘油三酯血症水平升高相关     

Major locus inheritance of apolipoprotein B in Utah pedigrees

A major locus that determines levels of apolipoprotein B (apoB) was revealed by likelihood analysis on 331 members of 36 pedigrees. The major locus explained 43.2% of the observed variance, with the remainder attributed to random environmental factors. Estimated mean apoB levels (mg/dl) were 110.5 +/- 2.5, 141.9 +/- 4.4, and 208.1 +/- 11.5 for low homozygotes, heterozygotes, and high homozygotes, respectively. The corresponding genotypic frequencies were 0.718, 0.259, and 0.023. The apoB locus explained 13% and 14% of the variance in total and low-density-lipoprotein cholesterol levels, respectively. Persons with elevated apoB had normal to high levels of total serum cholesterol and triglyceride and low to normal levels of high-density lipoprotein and apolipoprotein A-I. Sixteen members of three of the pedigrees were heterozygous for familial hypercholesterolemia (FH). Their apoB levels were estimated as 35.72 +/- 7.16 mg/dl above the apoB genotypic means, assuming that the two loci act independently. Therefore, two major loci, the FH locus and the apoB locus, affect two levels, apoB and LDL cholesterol.     

Variants of developmental genes (TGFA,TGFB3, and MSX1) and their associations with orofacial clefts: a case-parent triad analysis

We selected 262 case-parent triads from a population-based study of orofacial clefts in Norway, and examined variants of developmental genes TGFA, TGFB3, and MSX1 in the etiology of orofacial clefts. One hundred seventy-four triads of cleft lip cases (CL+/-P) and 88 triads of cleft palate only cases (CPO) were analyzed. There was little evidence for an association of any of these genes with CL+/-P. The strongest association was a 1.7-fold risk with two copies of the TGFB3-CA variant (95% CI=0.9-3.0). Among CPO cases, there was a 3-fold risk with two copies of the TGFA TaqI A2 allele, and no increase with one copy. Assuming this to be a recessive effect, we estimated a 3.2-fold risk among babies homozygous for the variant (95% CI=1.1-9.2). Furthermore, there was strong evidence of gene-gene interaction. While there was only a weak association of the MSX1-CA variant with CPO, the risk was 9.7-fold (95% CI=2.9-32) among children homozygous for both the MSX1-CA A4 allele and the TGFA A2 allele. No association of CPO with the TGFA variant was seen among the other MSX1-CA genotypes. In conclusion, no strong associations were found between CL+/-P and variants at these three genes. There was a possible recessive effect of the TGFA TaqI variant on the risk of CPO, with a 3-fold risk among children homozygous for the variant. The effect of this TGFA genotype was even stronger among children homozygous for the MSX1-CA A4 allele, raising the possibility of interaction between these two genes.     

单纯性肥胖儿童载脂蛋白E基因多态性的频率分布及其对血脂的影响研究

【目的】 探讨单纯性肥胖儿童载脂蛋白E(apolipoprotein E, ApoE)基因多态性的频率分布及对其血脂谱水平的影响。 【方法】 采用基因测序方法对100例单纯性肥胖儿童及100例正常对照组儿童进行ApoE基因多态性测定,另外抽取空腹静脉血作甘油三酯(triglyceride, TG)、胆固醇(total cholesterol, TC)、高密度脂蛋白(high-density lipoprotein cholesterol, HDL)、低密度脂蛋白(low-density lipoprotein cholesterol, LDL)、载脂蛋白A(apolipoprotein A, ApoA)、载脂蛋白B(apolipoprotein B, ApoB)检测,观察不同基因型和等位基因的分布情况,并与血脂的相关性进行分析。 【结果】 基因型E3/3频率分布最高,在70%之上,而含E3的杂合子(E2/3和E3/4)居中,二者之和超过20%,E2/2和E4/4表型的频率最低;与对照组比较,实验组肥胖儿童E2型等位基因有较高水平的TG(P＜0.05),E3型有较高的TG、TC、LDL水平和较低HDL、ApoA水平(P＜0.01),E4型有较高的TG、AopB水平和较低的HDL、ApoA水平(P＜0.05);肥胖组儿童中,与E3相比较,E4具有较高的TG、ApoB值和较低的HDL值,差异有统计学意义(P＜0.05),而E2具有较低的TC、LDL和ApoB水平,但是差异无统计学意义;携带不同等位基因的肥胖儿童的血脂异常率为E4＞E3＞E2(P＜0.01)。 【结论】 ApoE3/3是分布频率最高的基因型,ApoE4等位基因是血脂异常的风险基因之一,与肥胖儿童的血脂异常存在显著相关性。     

环境与apoE基因对肥胖儿童血脂水平影响的因素分析

目的 研究肥胖儿童血脂水平的影响因素,为高危儿童早期干预提供临床依据。方法 本实验为病例对照研究,对两组分别进行体格测量、家族相关病史、饮食及生活方式情况问询,并抽取空腹静脉血作甘油三酯(triglyceride,TG)、胆固醇(total cholesterol,TC)、高密度脂蛋白(high-density lipoprotein,HDL)、低密度脂蛋白(low-density lipoprotein,LDL)、载脂蛋白A(apolipoprotein A,apoA)、载脂蛋白 B(apolipoprotein B,apoB)检测,另外对两组儿童进行载脂蛋白E(apolipoprotein E,apoE)基因多态性等位基因测定,从环境和基因两方面分析影响肥胖儿童血脂的因素。结果 与对照组比较,肥胖儿童有较高的血脂异常率;父母高血脂、心血管家族史、高脂肪饮食和运动等对血脂异常的影响差异有统计学意义(P＜0.05);不同等位基因对血脂的影响不同,apoE3型等位基因有较高的TG、TC、LDL水平和较低HDL、apoA水平,apoE4型有较高的血TG、apoB水平和较低的HDL、apoA水平(P＜0.05)。肥胖儿童组内比较,以apoE3为参照,apoE2等位基因呈现出较低水平的TC、LDL和apoB(P＞0.05),而apoE4则具有较高的TG、apoB水平和较低的HDL水平(P＜0.01); 结论 父母高脂血症、心血管家族史、父母肥胖史、高脂肪饮食、运动及aopE基因多态性是肥胖儿童血脂异常的影响因素,其中apoE4等位基因是血脂异常的风险基因之一,与肥胖儿童的血脂异常存在显著相关性。     

脂蛋白脂酶基因多态性与高脂血症和肥胖的膳食易感性研究

目的:探讨脂蛋白脂酶(1ipoprotein lipase,LPL)基因PvuⅡ位点多态性在人群中的分布及其与血脂、体质指数和膳食因素的关系。方法:用聚合酶链反应和限制性片段长度多态性方法(PCR-RFLP)检测上海156名高脂血症和154名血脂正常的成年人的LPL-PvuⅡ位点多态性,同时对研究对象进行体格检查、膳食调查及血脂谱项目测定。结果:⑴高脂血症组和血脂正常组人群的基因型P+P+、P+P-和P-P-及等位基因P+和P-构成比差异无显著性意义,三种基因型及P+和P-在性别上无显著性差别。⑵P-P-基因型与非P-P-基因型的BMI水平有显著的统计学差异,P+P+型的BMI水平最高,控制相关影响因素后这种相关性仍然存在(P<0.05)。⑶膳食调查结果显示高脂血症人群中不同基因型的总能量、碳水化合物摄入量有差异。结论:LPL基因PvuⅡ位点P+等位基因研究对象的BMI和总能量、碳水化合物摄入量较高,此位点多态性不足以构成高脂血症的遗传危险因素。     

Lack of evidence for linkage between low-density lipoprotein subclass phenotypes and the apolipoprotein B locus in familial combined hyperlipidemia.

Low-density lipoprotein (LDL) subclass phenotype B, characterized by a predominance of small, dense LDL particles, appears to be a genetically influenced risk factor for coronary heart disease. Phenotype B, as determined by gradient gel electrophoresis, appears to be inherited in a manner consistent with the presence of a single major genetic locus, based on complex segregation analysis. Familial combined hyperlipidemia (FCHL) is a disorder characterized by elevations in total plasma cholesterol and/or triglyceride levels in probands and family members, variable lipoprotein phenotypes over time, and elevations in apolipoprotein B levels. Because apo B is the primary protein component of LDL particles, the present study was undertaken to determine whether LDL subclass phenotypes are controlled by the APOB locus in FCHL families. The evidence against linkage was very strong based on lod score analyses (total lod = -13.3), under assumptions that LDL subclass phenotypes are influenced by a major genetic locus and that the mode of inheritance and penetrance functions are known. Other methods requiring fewer assumptions also provided evidence against linkage, although the strength of this evidence was weaker. Thus the results demonstrate that the proposed gene responsible for LDL subclass phenotypes is unlikely to be the APOB gene in families with FCHL.     

脂蛋白脂酶基因多态性与代谢综合征的膳食易感性研究

目的探讨脂蛋白酯酶(lipoprotein lipase,LPL)基因Ser447Stop位点多态性在人群中的分布以及与代谢综合征(metabolic syndrome,MS)和膳食因素的关系。方法用聚合酶链反应和限制性片段长度多态性方法(PCR-RFLP)方法检测222名MS人群以及222名正常对照人群的LPL基因Ser447Stop位点多态性,同时对研究对象进行体格检查、生化指标测定和膳食调查。结果(1)SS、SX和XX三种基因型的频率分别为85.6%,13.3%和1.1%,符合Hardy-Weinberg定律。MS人群和对照人群的基因型SS、SX、XX及等位基因Ser447和Stop447构成比无差异,三种基因型及等位基因Ser447和Stop447在性别上无显著差异。(2)调整性别和年龄后,三种基因型的甘油三酯(TG)水平差异有显著性意义,SS型的TG最高,XX型的TG最低。(3)调整性别、年龄和体质指数后,三种基因型的蛋白质和碳水化合物摄入差异有显著性。(4)调整性别、年龄和体质指数后,不同基因型人群的蛋白质摄入与血清TG水平的负相关性有显著性意义。结论LPL基因Ser447Stop位点多态性与血清TG水平有关,与蛋白质摄入量有关联:该位点多态性可能会影响对于MS人群膳食干预的易感性。     

载脂蛋白B基因多态性与儿童血脂谱变异的关系

为了解载脂蛋白B(apoB)基因变异与儿童血脂谱的关系 ,对 30 8名 7～ 11岁在校儿童 (男 15 1人 ,女15 7人 )进行了血脂谱测定及apoB基因XbaⅠ位点多态性检测 (PCR RFLP方法 ) ,结果表明 :30 8名受检儿童基因型分布符合Hardy Weinberg遗传平衡定律 ,其中杂合突变型 (+ - )检出率为 13 3% ,未见纯合突变型(+ +) ;等位基因 (+)频率为 0 0 6 7,与国内报道相近 (0 0 33) ,但远低于白种人频率 (0 5 0 ) ;杂合突变型 (+ - )儿童低密度脂蛋白胆固醇水平为 2 17mmol L ,与野生型 (- - )儿童 (2 2 1mmol L)相比无明显差异 (P >0 0 5 ) ;高胆固醇组与正常组儿童apoB XbaⅠ位点基因型分布差异无显著性 (P >0 0 5 )。本研究未显示apoB XbaⅠ位点变异与儿童血脂谱有明显关联 ,这可能与样本大小、研究对象的选择等有关 ,而且正常儿童血脂谱受多基因遗传控制 ,单个基因位点的作用常是“微效”的 ,有待于在不同的人群中进行更广泛的研究及多基因多位点联合分析。     

A Period 2 genetic variant interacts with plasma SFA to modify plasma lipid concentrations in adults with metabolic syndrome

Genetic variants of Period 2 (PER2), a circadian clock gene, have been linked to metabolic syndrome (MetS). However, it is still unknown whether these genetic variants interact with the various types of plasma fatty acids. This study investigated whether common single nucleotide polymorphisms (SNPs) in the PER2 locus (rs934945 and rs2304672) interact with various classes of plasma fatty acids to modulate plasma lipid metabolism in 381 participants with MetS in the European LIPGENE study. Interestingly, the rs2304672 SNP interacted with plasma total SFA concentrations to affect fasting plasma TG, TG-rich lipoprotein (TRL-TG), total cholesterol, apoC-II, apoB, and apoB-48 concentrations (P-interaction < 0.001-0.046). Carriers of the minor allele (GC+GG) with the highest SFA concentration (>median) had a higher plasma TG concentration (P = 0.001) and higher TRL-TG (P < 0.001) than the CC genotype. In addition, participants carrying the minor G allele for rs2304672 SNP and with a higher SFA concentration (>median) had higher plasma concentrations of apo C-II (P < 0.001), apo C-III (P = 0.009), and apoB-48 (P = 0.028) compared with the homozygotes for the major allele (CC). In summary, the rs2304672 polymorphism in the PER2 gene locus may influence lipid metabolism by interacting with the plasma total SFA concentration in participants with MetS. The understanding of these gene-nutrient interactions could help to provide a better knowledge of the pathogenesis in MetS.     

北京市城区学龄儿童载脂蛋白E多态性与血脂谱水平的关系

目的 了解载脂蛋白E（ApoE)基因多态性与儿童血脂谱水平的关系。方法 采用聚合酶链反应－限制性内切酶图谱分析法,对307名7－11岁在校儿童进行血脂谱水平测定及ApoE基因多态性检测.结果 307名儿童最常见基因型E3／3检出率为54．7％,其他基因型依次为E4／3（23．8％）、E4／4（9．1％）、E3／2（8．1％）、E4／2（3．9％）、E2／2（0．3％）,不同性别基因型构成的差异无显性;常见等位基因E3频率为70．7％,E4、E2分别为23．0％和6．4％,其中E4频率明显高于国内其他报道,E2频率接近于国内报道;男童E4／3、E3／3基因型总胆固醇（TC,4．19、4．29、3．41mmol/L)、低密度脂蛋白－胆固醇（LDL－C）、载脂蛋白AI（ApoA I)、载脂蛋白B（ApoB)水平高于E3／2基因型,E4／2基因型TC（4．28和3．42mmol/L)、ApoA I水平高于E3／2基因型,女童不同基因型血脂谱水平的差异无显性;高胆固醇组与正常组儿童ApoE-Hha I位点基因型分布比较差异无显性;ApoE2可使TC水平降低0．377mmol/L,LDL-C水平降低0．329mmol/L。结论 ApoE基因多态性与男童血清胆固醇水平相关,E2等位基因携带TC、LDL－C、ApoB水平最低。     

Modeling of HLA class II susceptibility to Type I diabetes reveals an effect associated with DPB1.

In this report, we present evidence that the HLA class II DPB1 locus (or a locus with alleles in linkage disequilibrium with DPB1) contributes to Type I diabetes (IDDM) susceptibility in addition to the contribution of the HLA DR and DQ loci. The marker association segregation chi-square (MASC) method, which fits both genotype frequency and affected sib-pair identity-by-descent (IBD) distributions, was applied to 257 sib pairs affected with IDDM. Fitting DR-DQ as the sole HLA susceptibility loci was strongly rejected. Next, we considered the DPB1 contribution to disease susceptibility. Published reports indicate a predisposing role for alleles DPB1*0301 and DPB1*0202, including our previous stratification analyses of association data on this sample. IDDM probands were stratified into those not carrying the alleles DPB1*0301 and DPB1*0202 (group DPB1-A), and those carrying at least one copy of either allele (group DPB1-B). Both groups of probands have almost identical frequencies of DR and DQ haplotypes but significantly different IBD distributions in the subset of families with probands who do not carry the highly predisposing DR3/DR4 genotype. In these data, DPB1 (or a locus in linkage disequilibrium), in addition to DR-DQ, is involved in IDDM susceptibility and affects IBD in the HLA region. Addition of DPB1 in a genetic model of IDDM gives a better fit to the data than consideration of DR-DQ alone. Our results are consistent with previous reports implicating DPB1 in IDDM susceptibility.     

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。     

白细胞介素-8基因多态性与呼吸道合胞病毒诱发的急性支气管炎相关性研究

目的 探讨白细胞介素-8(IL-8)基因多态性与呼吸道合胞病毒诱发的急性支气管炎发生发展的相关性,为预测疾病发展提供科学依据。方法 2017年3－9月选取本院收治的80例呼吸道合胞病毒诱发的急性支气管炎患儿(病例组)以及30名健康儿童(对照组),根据疾病严重程度,将病例组分为轻症组(n=52)与中重症组(n=28)。采用酶联免疫吸附试验(ELISA)法检测三组受试者血清IL-8表达;采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术测定三组受试者IL-8基因-251、781多态性位点基因型,计算基因型频率与等位基因频率并进行比较。结果 对照组受试者血清IL-8表达[(4.35±0.84)] pg/ml低于其余两组,轻症组[(7.63±1.31)] pg/ml低于中重症组[(10.22±1.85)] pg/ml(P<0.05)。对照组受试者IL-8基因-251位点AA基因型频率(6.67%)低于其余两个病例组(23.08%、28.57%)(P<0.05)。对照组受试者IL-8基因-251位点A等位基因频率(33.33%)低于其余两个病例组(51.92%、55.38%)(P<0.05)。连锁分析结果显示,IL-8基因-251位点A等位基因与781位点C等位基因为紧密连锁,其共同组成的AC单体型与呼吸道合胞病毒诱发的急性支气管炎疾病易感性以及严重程度相关。结论 IL-8基因-251、781位点的AC单体型与呼吸道合胞病毒诱发的急性支气管炎发生发展相关。     

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。     

胆固醇酯转运蛋白基因多态性与肥胖及对膳食干预的影响

目的探讨胆固醇酯转运蛋白(CETP)基因多态性与肥胖的关系及其对肥胖膳食干预的影响。方法从血凝块中提取DNA,用聚合酶链反应和限制性片段长度多态性方法(PCR-RFLP)检测上海340名成年人的CETP基因TaqIB位点多态性;对研究对象进行体格检查并测定血脂;对其中的肥胖人群进行膳食干预,分析CETP基因多态性对干预效果的影响。结果(1)B1B1、B1B2和B2B2三种基因型的频率分别为35·6%、47·9%和16·5%,符合Hardy-Weinberg定律;B1等位基因为优势等位基因;肥胖组人群和正常组的基因型构成差异无显著性,控制相关影响因素后结果相同。(2)三种基因型的高密度脂蛋白(HDL)水平差异有显著性,B2B2型的HDL水平最高。控制环境影响因素后这种相关性仍然存在。(3)B1B2型膳食干预后HDL水平明显升高,这与其他基因型显著不同;控制基线HDL水平和性别因素后基因型对HDL水平改变没有影响。结论CETP-TaqIB位点B2B2基因型具有较高的血清HDL水平,成年肥胖人中此位点多态性无特殊性;基线HDL水平影响不同基因型的HDL对膳食干预的反应。     

Distribution and Determinants of Plasma Homocysteine Levels in Rural Chinese Twins across the Lifespan

Plasma homocysteine (Hcy) is a modifiable, independent risk factor for cardiovascular disease (CVD) and is affected by both environmental and genetic factors. This study aimed to describe the gender- and age-specific distribution of Hcy concentration for 1117 subjects aged 10–66 years, a subset of a community-based rural Chinese twin cohort. In addition, we examined environmental and genetic contributions to variances in Hcy concentration by gender and age groups. We found that the distribution pattern for Hcy varied by both age and gender. Males had higher Hcy than females across all ages. Elevated Hcy was found in 43% of male adults and 13% of female adults. Moreover, nearly one fifth of children had elevated Hcy. Genetic factors could explain 52%, 36% and 69% of the variation in Hcy concentration among children, male adults and female adults, respectively. The MTHFR C677T variant was significantly associated with Hcy concentrations. Smokers with the TT genotype had the highest Hcy levels. Overall, our results indicate that elevated Hcy is prevalent in the children and adults in this rural Chinese population. The early identification of elevated Hcy will offer a window of opportunity for the primary prevention of CVD and metabolic syndrome.     

高迁移率族蛋白B1多态性与肺癌化疗患者肺部感染严重程度的相关性

目的探讨高迁移率族蛋白B1(HMGB1)多态性和血清表达与肺癌化疗患者肺部感染及其严重程度的关系。方法选择2018年3月-2020年1月商丘市第一人民医院肿瘤内科收治的晚期肺癌化疗患者118例作为研究对象,根据其化疗期间是否发生肺部感染分为感染组(n=57)及非感染组(n=61)。采用聚合酶链式扩增反应(PCR)对两组患者外周血HMGB1 rs1412125(T>C)、HMGB1 rs2249825(C>G)进行基因分型,分析感染组HMGB1不同基因型患者、C-反应蛋白(CRP)、降钙素原(PCT)水平及肺部感染严重程度评分(Pneumonia severity index,PSI)。结果感染组HMGB1 rs1412125位点CC基因型、C等位基因频率, rs2249825位点GG基因型、G等位基因频率均显著高于非感染组(P<0.05);校正性别、年龄等因素后,多元Logistic回归结果显示,HMGB1 rs1412125位点CC基因型、C等位基因,rs2249825位点GG基因型、G等位基因是本地区晚期肺癌化疗患者肺部感染的危险因素;感染组患者HMGB1 rs1412125位点CC型血清HMGB1、CRP、PCT水平及PSI评分均高于TT型及TC型(P<0.05),感染组患者HMGB1 rs2249825位点GG型血清HMGB1、CRP、PCT水平及PSI评分高于CG型及CC型(P<0.05)。结论 HMGB1 rs1412125位点、HMGB1 rs2249825位点多态性与本地区肺癌化疗患者肺部感染易感性及严重程度有关,HMGB1 rs1412125位点CC型、HMGB1 rs2249825位点GG型为易感基因型。