中国汉族人群雌激素受体基因多态性及其与血脂关系的研究

目的：研究雌激素受体（ER）基因多态性在中国汉族正常人群中的分布及其与血脂的关系。方法：应用聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）方法,观察118名正常汉族人ER基因型,同时检测血脂并探讨两者的关系。结果：正常汉族人群中ER基因型以xx型、Pp型和Ppxx型出现频率最高,男女间差异不显著,且基因间血脂水平比较差异无显著性（P＞0．05）。与其它种族比较,ER基因型在中国正常人群中的分布与日本、韩国较为接近,而与瑞典、美国、意大利人群中的分布差异显著。结论：ER基因多态性与血脂水平无相关性,但在不同种族间分布有明显的差异,这种差异可能是导致一些疾病在不同种族间的发生、转归和预后不同的遗传因素之一。     

中国南方汉族人群DNA错配修复酶hMSH2基因遗传多态性分析

目的 获取DNA错配修复酶hMSH2基因在中国南方汉族人群中的基因型和基因频率等群体遗传学资料。方法 收集163名中国南方汉族人群的基础资料及血液标本，抽提血液DNA，用多重PCR法扩增hMSH2基因第6、第7外显子，并进行单链构象多态性分析及DNA序列分析。结果 检测出hMSH2基因第7外显子上的C18、A82、B39 3种基因突变类型，频率分别为0．0184、0．0031、0．0031，经检验符合Hardy—Weinberg平衡(P＞0．05)；C18型突变杂合度最高(0．0361)。结论 中国南方汉族人群中hMSH2基因第7外显子上存在3种突变型等位基因，其中C18型突变频率最高，是一种有用的遗传标记。     

中国汉族人群DC-SIGN和DC-SIGNR基因遗传多态性

目的了解中国汉族人群DC-SIGN和DC-SIGNR基因颈区重复序列的遗传多态性分布，获得相应位点的汉族人群的遗传学数据。方法应用PCR技术、琼脂糖凝胶电泳结合测序对DC-SIGN和DC-SIGNR基因的颈区重复序列分型，计算DC-SIGNR的多态信息含量。结果DC-SIGN多态性低，颈区绝大多数为等位基因7重复，该等位基因频率为0．9808，但亦检出少量的等位基因4、5、6、8等变异，而美国白人只含有等位基因6、8变异；DC-SIGNR存在高度多态性，多态信息含量为0．5312，存在4、5、6．7、8、9等位基因，检出16种基因型。6／5、7／4、7／5、7／6、7／7、9／5、9．／7、9／9基因型和5、6、7、9等位基因频率在中国汉族人群和美国白人中的分布构成差异有统计学意义（P〈0．01），与美国白人比较，中国汉族人群似乎存在更多的插入突变。结论中国汉人的DC-SIGN和DC-SIGNR基因型分布和基因频率与美国白人相比其差异有统计学意义，并有其独特的群体遗传学特征。     

广东汉族人群MICA和MICB微卫星多态性分布

目的　调查广东地区汉族人群 MICA基因第 5外显子和 MICB基因第 1内含子微卫星多态性分布。方法　应用聚合酶链反应和荧光 ( 6 - FAM)自动化检测技术 ,对广东地区共 10 6名无亲缘关系样本进行 MICA和 MICB微卫星基因分型 ,并计算这两个微卫星的基因频率、基因型频率、个体鉴别力、期望杂合性、多态性信息含量和非父排除率。结果　MICA和 MICB微卫星基因型分布符合 Hardy- Weinberg平衡。MICA A5基因频率最高为 0 .2 877,A4基因频率则最低为 0 .132 1;A5 - 5 .1( 14 .15 % )和 A5 - 5 ( 10 .38% )基因型分布频率较高。 MICB CA14等位基因频率最高为 0 .32 5 5 ,CA19、CA2 8等位基因频率最低为0 .0 0 4 7,未检出 CA2 7。 CA14 - CA14 ( 14 .15 % )基因型分布频率较高。结论　 MICA基因第 5外显子和MICB基因第 1内含子微卫星适合作为中国人群的遗传标志 ,用于人类学、遗传疾病基因连锁分析、法医学亲子鉴定和个体识别等研究领域     

中国汉族人群2型糖尿病易感性相关基因多态性

2型糖尿病(type 2 diabetes mellitus,T2DM)的发病与多个基因累加效应及多种环境因素相关.已在中国汉族人群中研究过的与T2DM易感性相关的基因多态性包括:全基因组相关研究中的CDKAL1、CDKN2A/B、SLC30A8、IGF2BP2、HHEX、FTO 以及KCNQ1基因;脂联素基因;核呼吸因子基因;葡萄糖激酶基因;肿瘤坏死因子α基因等.探索这些易感基因可以为人类治疗T2DM起到极大的推动作用.但至今已明确的基因依然很少,国内外的研究结果不尽相同,尚需进一步地深入研究.     

中国汉族人群DNA修复基因XRCC1多态性

-RFLP)对汉族人群XRCC1基因多态性进行检测.     

补体C6 T1674C单核苷酸多态性在中国汉族人群中的分布

目的获得人类补体第六成分(C6)T1674C多态性在中国汉族人群的分布特征。方法采用聚合酶链反应-单链构象多态性(polymerase chain reaction-single strand conformation polymorphism PCR-SSCP)结合核酸测序方法检测150例中国四川泸州汉族人群C6基因T1674C的基因型频率及等位基因频率。结果基因型TT、TC、CC的频率分别为44.67%、23.33%、32.00%,等位基因T、C频率分别为56.33%和43.67%,其基因型频率分布符合Hardy-weinberg平衡定律,个人识别机率为61.7%。结论中国汉族人群C6基因T1674C多态性个人识别能力高,重复性好,在人类遗传学研究及法医学个人识别中有较好的应用价值。     

中国汉族人群TNF-α基因启动子区的多态性研究

目的：研究中国汉族人群TNF-α基因启动子区的基因多态性。方法：采用PCR-SBT（PCR Sequencing Based Typing）方法进行TNF-α基因启动子区的多态检测。结果：采用PCR-SBT方法可以成功获得TNF-α基因启动子区的多态性结果并能够发现新的多态性位点；本次研究发现中国汉族人群TNF-α基因启动子区的多态性位点有：-1031、-863、-857、-572、-308、-238、-204和-163，其中-572和-204的多态性位点为首次报道；我国汉族人群该区域的核酸差异性为（11.00±0.46）×10-4，低于非洲人群；与Malawi人群相比，我国汉族人群-1031C、-308A、-238A出现频率较低，而-857T的频率却较高；与Gambian人群相比，-863A和-857T出现频率较高，-308A出现频率较低；我国汉族人群TNF-α基因启动子区的-1031C、-863A、-857T与-572C、-308A、-238、-204C、-163C有相关性。结论：采用PCR-SBT方法可以成功对TNF-α基因启动子区的基因多态性进行研究，我国汉族人群TNF-α基因启动子区的基因多态性可能存在独特的特点。     

汉族人群血管紧张素原基因的新单核苷酸多态性位点

应用改进的PCR－SSCP技术、多种聚丙烯酰胺凝胶电泳和PCR产物直接测序等方法，分析人的血管紧张素原（AGT）基因启动子区5远侧端的单核苷酸多态性（SNP）。在非变性胶上，发现不同样品的PCR产物（双链DNA分子）电泳迁移率不同；而在变性胶上，对应的单链DNA分子电泳迁移率相同；PCR产物直接测序的结果表明，在同一PCR扩增片段中同时存在两个SNPs位点（G－1074T，A－1179G）；通过476个不同样品的实验结果，进一步证实两个SNPs位点处于完全的连锁不平衡关系。GenBank同源性比较结果显示：A－1179G为中国汉族人群所特有。     

SDF1基因一个多态位点在中国人群中的分布

关于趋化因子受体与人免疫缺陷病毒（ｈｕｍａｎｉｍｍｕｎｏｄｅｆｉｃｉｅｎｃｙｖｉｒｕｓ，ＨＩＶ）的相关性研究于１９９５年起步，迅速成为当前ＨＩＶ研究热点。１９９６年，Ｏｂｅｒｌｉｎ等［１］和Ｂｌｅｕｌ等［２］发现了基质细胞衍生因子（ｓｔｒｏｍａｌｄｅｒｉｖｅｄｆａｃｔｏｒ１，ＳＤＦ１）作为趋化因子受体ＣＸＣＲ４的配体在ＣＤ＋淋巴细胞和ＨＩＶ１的融合中起作用，它是嗜淋巴细胞ＨＩＶ１株感染的体外潜在抑制因子，可阻断ＨＩＶ１侵入人体的通路。本实验的目的是观察ＳＤＦ１基因多态性在中国不同地区汉族…     

Association of the ARL15 rs6450176 SNP and serum lipid levels in the Jing and Han populations

The association of ADP-ribosylation factor-like 15 (ARL15) rs6450176 single nucleotide polymorphism (SNP) and serum lipid profiles has never been studied in the Chinese population. The present study was undertaken to detect the association of ARL15 rs6450176 SNP and several environmental factors with serum lipid levels in the Jing and Han populations. Genotypes of the SNP were determined in 726 unrelated subjects of Jing nationality and 726 participants of Han nationality. The genotypic and allelic frequencies of the SNP in Jing but not in Han were different between males and females (P < 0.001 and P < 0.05; respectively). The G allele carriers in Han had lower serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) B levels, and higher ApoA1/ApoB ratio than the G allele non-carriers (P < 0.05-0.01). The G allele carriers in Jing had lower serum TC, high-density lipoprotein cholesterol (HDL-C), ApoA1, ApoB levels and higher ApoA1/ApoB ratio than the G allele non-carriers (P < 0.05 for all). Subgroup analyses showed that the G allele carriers had lower TC and LDL-C levels in Han males; lower LDL-C and ApoB levels in Han females; lower ApoB levels and ApoA1/ApoB ratio in Jing males; and lower LDL-C levels in Jing females than the G allele non-carriers (P < 0.05-0.01). Multiple linear regression analysis showed that serum TC, LDL-C, ApoB levels and the ApoA1/ApoB ratio in Han; and TC, HDL-C and ApoA1 levels in Jing were correlated with the genotypes of the ARL15 rs6450176 SNP (P < 0.05-0.001). Serum lipid parameters were also associated with several environmental factors in both ethnic groups. These findings indicated that there may be a racial/ethnic- and/or sex-specific association of the ARL15 rs6450176 SNP and serum lipid levels.     

北方地区汉族消化道疾病中CYP2C19基因多态性分析

目的探讨中国北方地区汉族消化道疾病患者中CYP2C19基因多态性的频率分布及其与消化道疾病的相关性。方法采用数字荧光分子探针杂交法测定1 429例北方汉族消化道疾病的CYP2C19基因型,并根据其药物代谢活性分为超快代谢(ultra-rapid metabolizer,UM)型、快代谢(extensive metabolizer,EM)型、中间代谢(intermediate metabolizer,IM)型和慢代谢(poor metabolizer,PM)型四种。结果 CYP2C19等位基因*1、*2、*3和*17的频率分别为64.3%、29.7%、4.9%和1.0%。CYP2C19 UM型患者占1.2%(17例),EM型占41.5%(593例),IM型占45.3%(647例),PM型占12.0%(172例)。幽门螺旋杆菌总体感染阳性率为75.3%,不同CYP2C19代谢型患者的感染阳性率差异无统计学意义。在非萎缩性胃炎、萎缩性胃炎、消化性溃疡、反流性食管炎、Barrett食管和胃癌等消化道疾病之间CYP2C19的代谢型分布差异无统计学意义。10例胃癌患者中有8例为IM型。结论 CYP2C19 IM型和EM型是北方地区汉族消化道疾病中常见的代谢类型,CYP2C19*2、*3及PM型的频率高于欧洲人群,而CYP2C19*17及UM型频率低于欧洲人群。     

Association between the MARS rs6782181 polymorphism and serum lipid levels

Little is known about the association between the muscle Ras (MRAS) gene rs6782181 polymorphism and serum lipid levels. The aim of the present study was to investigate the association between the MRAS rs6782181 polymorphism and serum lipid levels in the Mulao and Han populations. A total of 632 subjects of Han and 629 unrelated subjects of Mulao nationalities were randomly selected from our previous stratified randomized samples. Genotypes of the MARS rs6782181 polymorphism were determined via polymerase chain reaction and restriction fragment length polymorphism. The subjects with GG genotype had higher serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein (Apo) B levels in Han, and higher serum TC and LDL-C levels in Mulao than the subjects with AA/AG genotypes (P < 0.05-0.01). Subgroup analyses showed that the subjects with GG genotype had higher TC, TG, high-density lipoprotein cholesterol (HDL-C), LDL-C, ApoAI and ApoB in Han males, lower ApoAI and the ratio of ApoAI to ApoB in Han females; and higher LDL-C levels in Mulao males but not in Mulao females than the subjects with AG/AA genotypes. The association of the MARS rs6782181 polymorphism and serum lipid levels is different between the Mulao and Han populations, or between males and females in the both ethnic groups. There may be an ethnic- and/or sex-specific association between the MRAS rs6782181 polymorphism and serum lipid levels in our study populations.     

Long non-coding RNA POLR2E rs3787016 is associated with the risk of papillary thyroid carcinoma in Chinese population

Long non-coding RNAs (LncRNAs) have been shown to be involved in cancer tumorigenesis and progression. Single nucleotide polymorphisms (SNPs) in the lncRNAs also play a vital role in carcinogenesis. We here explored the association between POLR2E rs3787016 and risk of papillary thyroid carcinoma (PTC) in a Chinese population, which was followed by a meta-analysis of POLR2E rs3787016 and cancer risk in Chinese population. A total of 409 PTC patients and 800 healthy individuals were enrolled in the present study. The POLR2E rs3787016 was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and was confirmed by sequencing. The POLR2E rs3787016T allele increased the PTC risk in Chinese population, particular in Chinese females. The meta-analysis further revealed that POLR2E rs3787016T allele was associated with an increased cancer risk in Chinese population. Collectively, the POLR2E rs3787016 may be used as a genetic biomarker to predict cancer risk in Chinese population.     

Solute carrier family 11 member 1 genetic polymorphisms rs17235409 and rs3731865 associate with susceptibility to extremity post-traumatic osteomyelitis in a Chinese Han population

Genetic variations in the solute carrier family 11 member 1 (SLC11A1) gene have been implicated in developing inflammatory disorders. However, it is still unclear whether such polymorphisms contribute to the pathogenesis of post-traumatic osteomyelitis (PTOM). Therefore, this study investigated the roles of genetic variations of the SLC11A1 gene (rs17235409 and rs3731865) in PTOM development in a Chinese Han cohort. The SNaPshot method was used for genotyping 704 participants (336 patients and 368 controls) for rs17235409 and rs3731865. Outcomes revealed that rs17235409 increased the risk of PTOM occurrence by dominant (p = .037, odds ratio [OR] = 1.44) and heterozygous models (p = .035, OR = 1.45), implying AG genotype as a risk factor for PTOM development. In addition, patients with AG genotype had relatively higher levels of inflammatory biomarkers than those with AA and GG genotypes, especially for the white blood cell count and C-reactive protein. Despite no statistically significant differences achieved, rs3731865 may reduce the PTOM susceptibility, suggested by the results of dominant (p = .051, OR = 0.67) and heterozygous (p = .068, OR = 0.69) models. In short, rs17235409 confers an elevated chance of developing PTOM, with AG genotype as a risk factor. Whether rs3731865 involves in the pathogenesis of PTOM requires further investigations.     

广西人群miRNA-107基因多态性分布特征及其与血脂的关系

目的探讨miR-107基因单核苷酸多态性(SNP)位点rs2296616 C/T在广西地区健康人群中的分布特点,对比其在不同种族间基因型及等位基因频率分布的差异,并进一步探讨rs2296616 C/T位点单核苷酸多态性(SNP)与血脂水平的相关性。方法采用多重单碱基延伸SNP分型技术(multiplex SNa Pshot)和DNA测序法,检测372例广西健康人rs2296616 C/T位点的多态性,用7600生化仪检测其血脂相关指标,并用统计学方法分别比较rs2296616C/T位点多态性在各种族人群间的分布差异及不同基因型间的血脂水平差异。结果广西人群miR-107基因rs2296616 C/T位点存在TT(91.1%)和CT(8.9%)两种基因型及T(95.6%)和C(4.4%)两种等位基因。该位点的基因型和等位基因型频率在广西人群不同性别间的比较,差异无统计学意义(P>0.05)。其基因型和等位基因频率与人类基因组单体型图(Hap Map)所公布的欧洲人、日本人、非洲人、印第安人和墨西哥人分型数据相比较,差异均有统计学意义(P<0.05),但与北京汉族人群比较,差异无统计学意义(P>0.05)。rs2296616 C/T位点两种基因型人群血脂之间比较,携带TT基因型人群的高密度脂蛋白胆固醇(HDL-C)与CT组比较,差异具有统计学意义(P<0.05)。结论广西人群miR-107基因rs2296616 C/T位点多态性与其他种族人群之间比较存在不同程度的差异;rs2296616 C/T位点多态性与HDL-C水平高低有关。     

The Association of Mitofusion-2 Gene Polymorphisms with Susceptibility of Essential Hypertension in Northern Han Chinese Population

Background: Mitofusion-2 (Mfn2) played an important role in regulating vascular smooth muscle cells proliferation, insulin resistance and endoplasmic reticulum stress, which were found to be involved in the development of hypertension. So we inferred that the Mfn2 gene may participate in the pathogenesis of hypertension. The aim of this study was to determine whether common single nucleotide polymorphisms (SNPs) in Mfn2 gene were associated with essential hypertension (EH) in northern Han Chinese.Methods: We genotyped 6 tagging SNPs of Mfn2 gene (rs2336384, rs2295281, rs17037564, rs2236057, rs2236058 and rs3766741) with the TaqMan assay in 626 hypertensive patients and 618 controls.Results: Logistic regression analysis indicated that CC+CA genotype of rs2336384 and AA+AG genotype of rs2236057 were significantly associated with increased risk of EH (OR=1.617, P=0.005; OR=1.418, P=0.031, respectively). GG genotype of rs2236058 and GG+CG genotype of rs3766741 were found to be significantly associated with decreased risk of EH (OR=0.662, P=0.023; OR=0.639, P=0.024).When stratified by gender, for rs2336384, rs2236057 and rs2236058, significant association was observed in males, but not in females. Haplotype analysis indicated that the CCAACC haplotype was positively correlated with EH and there was a negative correlation between ACAGGG haplotype and EH.Conclusions: This study demonstrated that Mfn2 gene polymorphisms were associated with essential hypertension in northern Han Chinese population, especially in male subjects.     

Distribution of MICA haplotypes in a Chinese Han population

The MICA gene encodes nonclassical major histocompatibility complex class I molecules, centromeric to HLA-B and telomeric to HLA-DRB1. The MICA genes are polymorphic. The immune response against MICA may correlate with a decrease in graft survival after transplantation. However, data on the frequency of MICA polymorphisms in different populations are limited. In this study, we determined MICA allelic frequencies in a Han population living in Guangdong Province in south China. A total of 15 MICA alleles were identified using sequence-based typing. The most frequent allele was MICA*010 (22.22%), followed by MICA*002:01(18.56%), MICA*008:01(16.32%), and MICA*019(14.93%). The MICA null gene (MICA*Del) exhibited a frequency of 1.743% in this population. MICA and HLA, MICA-HLA-B, and MICA-HLA-A/HLA-B/HLA-DRB1 haplotype frequencies were estimated. The most common 2-, 3- and 4-locus haplotypes were HLA-B*40:01-MICA*008:01 (13.70%), HLA-A*11:01-B*40:01-MICA*008:01(8.25%), and HLA-A*33:03-B*58:01-DRB1*03:01-MICA*002:01(5.22%). A new MICA allele, MICA*061, was identified and appears to be evolutionarily related to MICA*012:01. This study provides high-resolution information on the distribution of haplotypes with MICA, HLA-A, HLA-B, and HLA-DRB1 in China. This information should help determine the mechanisms underlying diseases and allotransplant rejection associated with MICA polymorphisms in the southern Chinese Han population.     

父亲生育年龄与子女罹患精神分裂症的相关性分析

目的 探讨在汉族人群中生父生育年龄与子女罹患精神分裂症风险的相关性.方法 收集351例精神分裂症患者与199名健康志愿者进行病例对照研究.将患者生父母生育年龄分组,以26～30岁组作为参照组,分别对生父母生育年龄的不同组别进行分类变量的Logistic回归分析,并予被试年龄、性别、生母或生父生育年龄等进行校正.结果 校正后,与生育年龄在26~30岁的父亲相比,31~35岁、36~40岁、≥41岁3个年龄组父亲子女罹患精神分裂症的OR值分别为3.834、8.805和11.619(P<0.05);父亲生育年龄≤25岁时,子女罹患精神分裂症的OR值为0.877(P>0.05).生母各生育年龄组P值无统计学意义.结论 生父生育年龄与子女罹患精神分裂症显著相关;生父生育年龄越大,子女罹患精神分裂症的风险越高.推测这一风险作用的生物学机制是随着男性年龄的增长,生殖细胞的分化成熟过程中会不断积累新发突变或父系基因印迹异常.

Abstract：

Objective To investigate whether advanced paternal age is related to an increased risk of schizophrenia in Chinese Han population. Methods A case-control design study was performed. Three hundred and fifty-one patients with schizophrenia and 199 unrelated healthy volunteers were recruited. By using Logistic regression, paternal age was divided into five categories, and maternal age into four categories. Setting the paternal age of 26-30 years as reference, the OR, P values and 95% CI of the other paternal age categories were analyzed, respectively. The participant's sex, age and parental age at birth were used as covariants for adjusting confounding effects. Results The OR for schizophrenia in offspring whose paternal age at birth of 31-35 years, 36-40 years, and ≥41 years categories were 3.834, 8.805, and 11.619 respectively. The advanced maternal age had no significant effects on the risk for schizophrenia in offspring. Conclusion The advanced paternal age was associated with elevated risk for schizophrenia in offspring among a Han Chinese population. Putative biological mechanisms may include accumulated de novo mutations and alterations in epigenetic regulations with aging in spermatogenesis.