VNTR polymorphism of human IL1RN in Chinese Han and She ethnic populations

Interleukin 1 receptor antagonist (IL‐1Ra) is an important anti‐inflammatory molecule encoded by the IL1RN gene. The polymorphism of IL1RN characterized by variable numbers of an 86 bp tandem repeat (VNTR) sequence in intron 2 has been described. Moreover, frequencies of the IL1RN alleles vary among different ethnics. In the present study, we analysed the IL1RN polymorphism in intron 2 in 256 Chinese Han and 252 Chinese She individuals. Four alleles including IL1RN*1, *2, *3 and IL1RN*4 were identified in this study. Data revealed that the distribution of the IL‐1RN genotypes and allele was significantly different between the two Chinese populations (P < 0.001). Among them, 66.8% (171/256) and 86.5% (218/252) were homozygous for the allele IL‐1RN*1 in Chinese Han and She individuals respectively. Homozygosity for allele IL‐1RN*2 was only observed in Chinese Han with the percentage of 0.8% (2/256). Heterozygosity for IL‐1RN*1/2, IL1RN*1/3 and IL1RN*1/4 was 30.9% (79/256), 0.4% (1/256) and 1.2% (3/256) in Chinese Han, whereas only heterozygosity for IL‐1RN*1/2 was found in Chinese She (13.5%, 34/252). Frequencies of the most common allele IL‐1RN*1 and IL‐1RN*2 were 83.0% and 16.2% for Chinese Han and 93.3% and 6.7% for Chinese She respectively. The rare allele IL‐1RN*3 and IL‐1RN*4 was only observed in the Chinese Han population with the frequency of 0.2% and 0.6% respectively. Our findings suggested that the ethnic background plays an important role in IL‐1Ra gene variation in different populations.     

中国苗族、布依族、土族和独龙族群体中细胞色素P450 2C19基因座遗传多态性分析

目的 研究细胞色素P450 2C19（cytochrome P450 2C19,CYP2C19）在中国4个民族群体中的基因型和基因频率。方法 采用聚合酶链反应与限制性片段长度多态性技术，分析了无血缘关系的苗族、布依族、土 和独龙族人群的基因型。结果 CYP2C19＊2突变基因在苗族、布依族、土圹和独龙族人群中的频率分别为0.292、0.329、0.315和0.349。4个群体经检验均符合Hardy-Weinberg平衡（P＞0.05）。结论 中国苗族、布族、土族和独龙族人群的CYP2C19＊2突变基因频率与欧洲、非洲人群差异较大，而与亚洲人群相近。     

我国汉族人群α1基因数目可变串联重复序列分布特征的研究

目的：研究我国汉族人群免疫球蛋白α1基因中3个数目可变串联重复序列(VNTR)多态性分布特征，及其与已报道的高加索人群相比较的特点。 方法: 从现存数据库中寻找α1基因内的3个VNTR位点，即α1基因3’端的hs1,2增强子内的VNTR1、其上游6 Kb 的VNTR2和位于α1基因第5外显子的E5VNTR。 提取201例广东汉族人基因组DNA，PCR分别扩增含上述3个VNTR位点片段，2%－3％凝胶电泳分带鉴定基因型，并以测序证实。 结果: 与高加索人群比较我国汉族人群α1基因 VNTR1多态性分布特征表现为：C（3次重复）等位基因频率明显升高（10.0% vs 1.0%）， A（1次重复）等位基因频率偏低（30.3% vs 36.1%-39.4%）, 差异显著（χ2=72.85，P＜0.01）。 基因型BB占37.8％， AB占32.3％，AA占12％，BC占11.4％, AC占4.5％, CC占2.0％， BC、AC基因型分布频率显著高于高加索人群，而AB型分布频率显著低于高加索人群（χ2=73.77，P＜0.01）。另外两个数据库中报道的VNTR位点（VNTR 2及E5VNTR）在我们所测人群中呈均一分布,PCR产物长度分别为136 bp(VNTR 2)和535 bp(E5VNTR)。 结论: 我国汉族人群α1基因 VNTR多态性分布与基因组数据库中基于高加索人群的资料不尽相同，其中Iα1 hs1,2 VNTR1多态性不同于高加索人群，突出表现为C等位基因频率及BC、AC基因型频率显著高于高加索人群。而VNTR2和E5VNTR在被检人群中未见多态性。本研究弥补了现存数据库中缺乏我国汉族人群相应数据的不足, 同时为以α1基因为候选基因找寻疾病基因的研究提供了可靠的数据。     

中国四个人群中MICA基因多态性研究

目的：了解中国４个人群中ＭＩＣＡ基因第５外显子（ＧＣＴ）ｎ位点的遗传２多态性并从遗传学的角度提供白马藏族起源的初步证据。方法：４１１个无血缘关系个体的血标本或唾液标本分别采自四川平武县白巴藏族、西藏拉萨和云南中甸县藏族、成都地区汉族以及四川茂县羌族。以１对跨越ＭＩＣＡ基因第５外显子ＧＣＴ重复序列区的引物扩增基因组ＤＮＡ,产物用变性聚丙烯酰胺凝胶电泳分离,银染显色分析。结果：在４个群体中均检测出５种已报道的等位片段,并均以Ａ５最常见,在白马藏族、藏族、成都汉族和羌族中的频率分别为０．３２５、０．３４５、０．３９０和０．３１９。Ａ５．１在成都汉族和羌族中占第２位,频率分别为０．２３０和０．２９３,Ａ４和Ａ９在白马藏族和藏族中分别占第２位,频率分别为０．２５４和０．２７２。上述各等位基因分布在４个群体中存在差异,尤其     

广西壮族人群ICAM-1基因多态性及血清水平与脑梗死关系的研究

探讨细胞间黏附分子1(ICAM-1)基因K469E多态性各等位基因及基因型在广西壮族脑梗死患者中的分布频率,初步分析其基因及血清水平与脑梗死的关系。采用聚合酶连反应-限制性片段长度多态性(PCR-RFLP)和DNA序列测定法检测19例脑梗死及210例对照者ICAM-1基因第6外显子K469E多态性,同时采用酶联免疫吸附试验(ELISA)检测脑梗死和对照者血清ICAM-1水平。脑梗死组ICAM-1血清水平显著高于对照组(P<0.01),ICAM-1基因K469E基因频率和等位基因频率在脑梗死组和对照组比较差异有显著性(P<0.05),等位基因频率的相对风险分析发现,E等位基因携带者患脑梗死的风险是K等位基因的1.454倍(OR=1.454,95%CI1.090～1.940),携带E等位基因的脑梗死患者ICAM-1血清水平显著高于不携带者(503.31±141.32)ng/ml和(489.80±122.43)ng/ml,(P<0.01)。ICAM-1基因K469E多态性与脑梗死的发病具有相关性,E等位基因可能是广西地区壮族人脑梗死发病的遗传易感基因,携带E等位基因的个体可能通过促进ICAM-1的高度表达进而增加脑梗死的发病风险。     

Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels

Interleukin-1-receptor antagonist (IL-1RA) modulates the biological activity of the proinflammatory cytokine interleukin-1 (IL-1) and could play an important role in the pathophysiology of inflammatory and metabolic traits. We genotyped seven single nucleotide polymorphisms (SNPs) that capture a large proportion of common genetic variation in the IL-1RN gene in 1256 participants from the Invecchiare in Chianti study. We identified five SNPs associated with circulating IL-1RA levels with varying degrees of significance (P-value range=0.016-4.9 x 10(-5)). We showed that this association is likely to be driven by one haplotype, most strongly tagged by rs4251961. This variant is only in weak linkage disequilibrium (r(2)=0.25) with a previously reported variable number of tandem repeats polymorphism (VNTR) in intron-2 although a second variant, rs579543, that tags the VNTR (r(2)=0.91), may also be independently associated with IL-1RA levels (P=0.03). We found suggestive evidence that the C allele at rs4251961 that lowers IL-1RA levels is associated with an increased IL-1beta (P=0.03) level and may also be associated with interferon -gamma (P=0.03), alpha-2 macroglobulin (P=0.008) and adiponectin (P=0.007) serum levels. In conclusion, common variation across the IL-1RN gene is strongly associated with IL-1RA levels.     

中国汉族和维吾尔族MRC1基因多态性与肺结核病的相关性

目的 探讨中国汉族和维吾尔族人群MRC1基因多态性与肺结核病易感性的联系. 方法 应用PCR和DNA测序技术,对中国汉族454例和维吾尔族595例人群的MRC1基因的第7号外显子6个SNPs(G1186A、G1195A、T1212C、C1221G、C1303T和C1323T)基因型及基因频率分布进行检测,并进行连锁不平衡分析. 结果 中国汉族人群中G1186A位点等位基因G型分布频率在肺结核病组和正常健康组之间存在显著差异(P =0.037;OR =0.76;95％ CI:0.58～0.98);AG基因型在两组之间存在显著性差异(P ＜0.01;OR=0.57;95％ CI:0.37 ～0.87).在年龄和性别校正后,G1186A位点在显性(P＜0.01;OR=0.59;95％ CI:0.40～0.87)、超显性(P =0.045;OR =0.69;95％ CI:0.47～0.99)和加性模式(P =0.041;OR=0.76;95％ CI:0.59 ～0.99)时,与肺结核病存在显著相关性.在维吾尔族人群中G1186A位点的等位基因G的分布频率在两组之间的分布具有显著性差异(P =0.031;OR=1.29;95％CI:1.02 ～ 1.62);基因型分析发现AA基因型在两组之间也存在显著性差异(P=0.033;OR=1.64;95％ CI:1.04～2.60);在年龄和性别校正后,G1186A位点在加性模式下与肺结核病存在相关性(P=0.033;OR=1.28;95％ CI:1.02～1.61).连锁不平衡分析发现,构建的单体型GGTCCT(P=0.032;OR =0.75;95％ CI:0.57 ～0.97)和GGTCCC(P=0.044;OR=0.57;95％ CI:0.33 ～0.99)与肺结核病存在显著的相关性. 结论 MRC1基因G1186A位点与中国人群肺结核病相关.     

IL-1 receptor antagonist gene polymorphism in idiopathic recurrent spontaneous abortion in a Chinese Han population

Interleukin-1 receptor antagonist (IL-1Ra) has been supposed to play important roles in pregnancy. The purpose of this study was to evaluate the association between the polymorphisms of IL-1Ra gene (IL1RN) variable number tandem repeat (VNTR) in intron 2 with idiopathic recurrent spontaneous abortion (RSA). Ninety-two RSA patients and hundred normal women with at least one live birth and no history of miscarriage were included in the study. Frequencies of the IL1RN alleles and genotypes were determined. Data revealed that the prevalence of IL1RN allele and genotype was not significant between the RSA and control group (all P > 0.05). Our finding indicated that the polymorphism VNTR of IL1RN gene in intron 2 may not be a risk factor for RSA in the Chinese Han population.     

VNTR3' polymorphism of apoliproprotein B gene in obese people

Apolipoprotein B (apo B) is the major component of LDL, VLDL and chylomicrons. Variations of lipid concentrations in obese people result from obesity, nutritional and genetic factors. Many genetic polymorphisms of the apo B have been described, associated with variation of lipid concentrations. The aim of the present study was to assess the effect of VNTR3' polymorphism of the apoB gene on lipid and lipoprotein concentrations in overweight subjects. 234 unrelated outpatients (160 women and 74 men, aged 39.3 y 10.5; BMI: 32.8 kg/m2 4.7) were recruited. Using the polymerase chain reaction followed by electrophoresis in polyacrylamide gels, 15 different alleles have been identified. Among them four have been observed less than 5 times in our study. Alleles with 21, 25, 35 and 42 repeats have been observed once. The most frequent is VNTR36 allele (38%), followed by alleles 34, 30, 48, and 46 repeats whose frequencies are 20, 9, 8, and 7% respectively. The possible association between alleles of the VNTR3' of the apoB and anthroprometric and lipid variables was examined. Subjects with 50 repeat allele had significantly higher BMI, and subjects with 32 repeat allele had significantly higher HDL-C and ApoAI levels. Our study confirms in the obese subjects, results published in the general litterature, and shows that the apoB has an important role in the metabolism of plasma lipids and most particulary its gene variants.     

中国人内源性高甘油三酯血症载脂蛋白E基因多态性的研究

目的 探讨中国人内源性高城油三酯血症（endogenous hypertriglyceridemia,HTG)患者载脂蛋白E（apolipoprotein E,apoE)基因多态性及其与血脂和载脂蛋白水平的关系。方法 采用聚合酶链反应－限制性片段长度多态性分析方法,分别对225例HTG患者及230名血脂正常者的apoE基因型、空腹血脂及载脂蛋白AⅠ、AⅡ、B100、CⅡ、CⅢ、E进行了分析。结果 HTG患者的体重指数(BMI)` 清甘油三酯（TG）、总胆固醇（TC）、非高密度脂蛋白胆固醇（nHDLC)水平较对照组显著升高,血清高密度脂蛋白胆固醇（HDLC）则显著降低（P＜0．001）,并伴有载脂蛋白水平的异常。HTG组与对照组apoE基因型及等位基因频率分布均以E3／3和ε3最高,HTG组的ε2等位基因有增高的趋势（P＞0．05）。对照组ε2等位基因携带者血清TG和apoE水平较ε3和ε4等位基因携带者显著升高（P＜0．001）,其低密度脂蛋白胆固醇（LDLC）水平及apoE/ApoC Ⅲ比值则显著降低（P＜0．001）。结论 ε2等位基因与血清TG和apoE水平升高及LDLC水平降低有关,apoE/apoC Ⅲ比值降低可能与HTG患者血TG水平升高有关。     

Implication of IL-33 gene polymorphism in Chinese patients with Alzheimer's disease

Interleukin-33 (IL-33), a newly described member of the IL-1 family, is located on chromosome 9p24, a chromosomal region of interest in Alzheimer's disease (AD) defined by many genome-wide studies. Three intronic rs1157505, rs11792633, and rs7044343 single nucleotide polymorphisms (SNPs) within IL-33 have recently been reported to be associated with risk of AD in Caucasian populations. In order to assess the involvement of the IL-33 polymorphisms in the risk of developing late onset AD (LOAD), we analyzed the genotype and allele distributions of these 3 polymorphisms in 704 Han Chinese subjects. The minor alleles of the rs11792633 polymorphism within IL-33 was significantly associated with a reduced risk of LOAD (odds ratio [OR] = 0.73, p = 0.005). Furthermore, rs11792633 polymorphism was still strongly associated with LOAD (dominant model: OR = 0.67, p = 0.015; recessive model: OR 0.57, p = 0.021; additive model: OR = 0.71, p = 0.004) after adjusting for age, gender, and the apolipoprotein E (APOE) ε4 status. Our results support the evidence that genetic variants of IL-33 affect susceptibility to LOAD in Han Chinese.     

Human dopamine transporter gene polymorphism (VNTR) and alcoholism

The dopamine transporter (DAT1) is responsible for taking released dopamine back up into presynaptic terminals and terminating dopaminergic activity. It has been shown that cocaine binds to the dopamine transporter and blocks dopamine reuptake in a fashion that correlates with cocaine reward and reinforcement. To determine the role of this gene in the development of alcoholism, we have used two approaches, relative risk and haplotype relative risk. The relative risk approach involved 162 alcoholic probands who were categorized into type I and type II, and 89 unrelated normal controls. In the haplotype relative risk approach, 29 trios (father, mother, and proband) were genotyped with dopamine transporter gene polymorphism. Comparison of allele frequencies between total alcoholics, subtypes of alcoholics, and normal controls were negative. The results of haplotype relative risk, differences between alleles transmitted and nontransmitted, were also negative. However, both approaches produced similar results. Therefore, we concluded that the VNTR polymorphism in DAT1 gene is not associated with alcoholism susceptibility genes in our samples. Am. J. Med. Genet. 74:480–482, 1997. © 1997 Wiley-Liss, Inc.     

Indian ethnic populations characterized by dopamine (D4) receptor VNTR polymorphism

BACKGROUND: The human dopamine receptor D4 gene (DRD4) contains a 48-bp tandem repeat in exon 3 and shows alleles varying between repeats 2 and 11. The gene shows a high level of expression in the prefrontal cortex of the brain and association of particular alleles of this locus with various neuropsychiatric and personality disorders have been reported. OBJECTIVE: The present study reports allele frequency distribution at the DRD4 variable number tandem repeat (VNTR) locus among five ethnic populations of India. This background information is fundamental to the field of pharmacogenetics for disease susceptibility and association studies. SUBJECTS AND METHODS: Three hundred and thirty two healthy unrelated adult individuals belonging to five ethnic groups: Konkanastha Brahmins, Marathas, Ezhavas, Nairs and Muslims, have been typed. Genomic DNA, extracted from peripheral blood, was PCR amplified using a two-enzyme system. The use of ALF Express DNA sequencer was found to be helpful for large-scale population genotyping. Statistical analysis was performed using the POPGENE and DISPAN programs. RESULTS: A total of eight alleles ranging from repeat 2 to repeat 9 were observed. Allele 4 was the predominant allele among all the five populations, consistent with the data on other world populations. A rare allele 9 was detected exclusively among Marathas. The observed heterozygosity was low, ranging from 0.38 to 0.54 while other parameters like Polymorphism Information Content (PIC) and Power of Discrimination (PD) showed moderate values. The populations were in genetic equilibrium when tested under Hardy-Weinberg expectations. CONCLUSION: The allele frequency estimates for DRD4 provided here will contribute towards developing an informative database for this functionally relevant locus. This will prove useful when studying the association between genetic factors and pathogenesis of disease in Indian populations and will address the concern of biased results of association due to population admixtures.     

IL-1β基因多态性对RA患者PBMC IL-1β mRNA表达的影响

目的:探讨类风湿关节炎(RA)患者中白细胞介素-1β(IL-1β)基因多态对IL-1β mRNA表达的影响。方法: 应用荧光定量RT-PCR技术检测不同IL-1β基因型的RA病人外周血单个核细胞(PBMC)中IL-1β mRNA表达量的差异。结果: 携带IL-1β(-511)纯合子等位基因2组RA病人PBMC表达IL-1β mRNA量明显较非纯合子及正常人组为高(均P<0.01)。结论: IL-1β基因多态性改变对IL-1β mRNA的表达产生影响,IL-1β(-511)纯合子等位基因2促进了IL-1β mRNA的表达。     

IL-1基因多态性对类风湿关节炎病情及IL-1蛋白表达影响

目的:探讨白细胞介素-1α(IL-1α)和白细胞介素-1β(IL-1β)基因多态性对类风湿关节炎(RA)病情及对IL-1β产生的影响。方法:检测136例RA病人及102例正常人的IL-1等位基因分布,其中72例病人系已明确患病2年内出现关节破坏者,IL-1基因多态性检测采用PCR-RFLP法,同时分析不同类型基因型病人外周血单个核细胞受刺激后分泌IL-1β水平的不同。结果:IL-1α等位基因1、2的频率和携带率在RA组及正常人组无显著差异。IL-1β纯合子等位基因2频率在2年内出现骨侵蚀组明显高于2年内未出现骨侵蚀组,IL-1β纯合子等位基因2携带病人组具有较高的血沉及关节肿胀、压痛指数,从携带IL-1β纯合子等位基因2病人中分离出的外周血单个核细胞经脂多糖刺激后分泌的IL-1β量明显高于其它组病人。结论:RA与IL-1β基因多态显著相关,IL-1β等位基因2促进IL-1β分泌,IL-1β等位基因2的检测可作为预测RA严重性的一个有用指标。     

中国人群IL-1R1基因变异及其对跨膜区功能影响的预测

目的　检测中国人白细胞介素 1Ⅰ型受体基因 (interleukin 1receptortypeⅠ ,IL 1)调控区和编码区的单核苷酸多态性 (singlenucleotidepolymorphisms ,SNPs) ,并初步探讨其可能对中国人IL 1R1的功能影响。方法　采用直接测序的方法检测基因的 5′区、编码区、部分内含子区和 3′区 ,以确定中国人群中IL 1R1基因SNP的位置和类型 ,用生物信息学方法对编码区SNP的功能进行了预测。结果　在 964 3bp的测序长度中 ,共发现了 16个SNP ,包括 5′区 4个 ,内含子区 4个 ,编码区 1个 ,3′非编码区 7个。其中一个SNP能引起IL 1R1跨膜区氨基酸的替代 ,生物信息学分析显示它能够引起跨膜区结构的改变。结论IL 1R1基因变异可能对IL 1R1的功能产生影响。     

Indian ethnic populations characterized by dopamine (D4) receptor VNTR polymorphism

Background:?The human dopamine receptor D4 gene (DRD4) contains a 48-bp tandem repeat in exon 3 and shows alleles varying between repeats 2 and 11. The gene shows a high level of expression in the prefrontal cortex of the brain and association of particular alleles of this locus with various neuropsychiatric and personality disorders have been reported.

Objective:?The present study reports allele frequency distribution at the DRD4 variable number tandem repeat (VNTR) locus among five ethnic populations of India. This background information is fundamental to the field of pharmacogenetics for disease susceptibility and association studies.

Subjects and methods:?Three hundred and thirty two healthy unrelated adult individuals belonging to five ethnic groups: Konkanastha Brahmins, Marathas, Ezhavas, Nairs and Muslims, have been typed. Genomic DNA, extracted from peripheral blood, was PCR amplified using a two-enzyme system. The use of ALF?Express DNA sequencer was found to be helpful for large-scale population genotyping. Statistical analysis was performed using the POPGENE and DISPAN programs.

Results:?A total of eight alleles ranging from repeat 2 to repeat 9 were observed. Allele 4 was the predominant allele among all the five populations, consistent with the data on other world populations. A rare allele 9 was detected exclusively among Marathas. The observed heterozygosity was low, ranging from 0.38 to 0.54 while other parameters like Polymorphism Information Content (PIC) and Power of Discrimination (PD) showed moderate values. The populations were in genetic equilibrium when tested under Hardy–Weinberg expectations.

Conclusion:?The allele frequency estimates for DRD4 provided here will contribute towards developing an informative database for this functionally relevant locus. This will prove useful when studying the association between genetic factors and pathogenesis of disease in Indian populations and will address the concern of biased results of association due to population admixtures.

Résumé. Le gène D4 récepteur de la dopamine humaine (DRD4) contient un tandem répété de 48-bp en exon 3 et présente des allèles variant entre les répétitions 2 et 11. Le gène présente un niveau élevé d’expression dans le cortex frontal du cerveau et on a fait état de diverses affections neuropsychiatriques et de troubles de personnalité en association avec les gènes de ce locus.

Objectif: Cette étude concerne la distribution de fréquence allélique du nombre variable de répétitions de tandem (VNTR) au locus DRD4 dans cinq populations ethniques de l’Inde. Cette information d’arrière plan est fondamentale pour les études de susceptibilité et d’associations pathologiques en pharmacogénétique.

Sujets et méthodes: On a typé 332 adultes sains et non apparentés, appartenant à cinq groupes ethniques : Konkanastha Brahmin, Maratha, Ezhava, Nair et des musulmans. L’ADN génomique extrait du sang périphérique, a été amplifié par PCR au moyen d’un système de deux enzymes. L’utilisation du séquenceur d’ADN ALF^TM a été efficace pour le génotypage à grande échelle. Les analyses statistiques ont été effectuées à l’aide des programmes POPGENE et DISPAN.

Résultats: On a observé au total huit allèles, variant de la répétition 2 à la répétition 9, l’allèle 4 étant prédominant dans les cinq populations, en accord avec les données mondiales. Un rare allèle 9 a été trouvé chez Maratha exclusivement. L’hétérozygosité observée est faible, variant de 0,38 à 0,54, tandis que d’autres paramètres tels le Contenu d’Information Polymorphique et le Pouvoir de Discrimination présentent des valeurs modérées. Les populations testées par rapport aux proportions de Hardy-Weinberg apparaissent en équilibre génétique.

Conclusion: Ces estimations de fréquences alléliques pour DRD4 contribueront au développement d’une base de données sur ce locus. Ceci sera utile pour l’étude de l’association entre facteurs génétiques et pathogenèse dans les populations indiennes et nourrira le problème des biais de résultats d’association dus aux mélanges de populations.

Zusammenfassung.Hintergrund: Das menschliche Dopaminrezeptor-D4-Gen (DRD4) enthält ein 48-bp-Tandem-Repeat in Exon 3 und zeigt Allele, die zwischen den Repeats 2 und 11 variieren. Das Gen zeigt eine starke Ausprägung im präfrontalen Cortex des Gehirns, und es wurden Beziehungen zwischen besonderen Allelen dieses locus und verschiedenen neuropsychiatrischen und Persönlichkeitsstörungen berichtet.

Vorhaben: Die vorliegende Untersuchung berichtet über die Verteilung der Allelhäufigkeiten am DRD4-VNTR-locus (variable number tandem repeat, VNTR, verschiedene Anzahl von Tandem-Repeats) bei fünf ethnischen Bevölkerungsgruppen in Indien. Diese Hintergrundinformation ist wesentlich auf dem Gebiet der Pharmakogenetik für Krankheitsanfälligkeit und Assoziationsstudien.

Probanden und Methoden: 332 gesunde, nicht verwandte Personen aus fünf ethnischen Gruppen, Konkanastha Brahmins, Marathas, Ezhavas, Nairs und Moslems, wurden typisiert. Genomische DNS aus peripherem Blut wurde PCR-amplifiziert unter Verwendung eines 2-Enzymsystems. Die Verwendung von ALF?Express DNA Sequencer wurde als hilfreich bei der genetischen Typisierung größerer Bevölkerungsgruppen angesehen. Statistische Analysen wurden mit POPGENE- und DISPAN-Programmen durchgeführt.

Ergebnisse: Insgesamt wurden acht Allele mit Repeats zwischen 2 und 9 beobachtet. Das Allel 4 war unter allen fünf Populationen vorherrschend, passend zu Daten von anderen Völkern dieser Erde. Ein seltenes Allele 9 wurde ausschließlich bei den Marathas gefunden. Die beobachtete Heterozygotie war niedrig und reichte von 0,38 bis 0,54, während andere Parameter wie der Gehalt an Information betreffend Polymorphismus (Polymorphic Information Content) und die Unterscheidbarkeit (Power of Discrimination) mäßige Ausprägungen zeigten. Die Populationen waren bei Prüfung unter Hardy–Weinberg-Erwartungen im genetischen Äquilibrium.

Zusammenfassung: Die hier vorgenommene Schätzung der Allelhäufigkeit für DRD4 wird zur Entwicklung einer informativen Datenbasis für diesen funktionell bedeutsamen locus beitragen. Dies wird sich als hilfreich für die Untersuchung der Beziehung zwischen genetischen Faktoren und der Pathogenese von Krankheiten in der Indischen Bevölkerung erweisen und wird Bedenken berücksichtigen hinsichtlich möglicher Beeinflussung von Ergebnissen aufgrund ethnischer Durchmischung.

Resumen. Antecedentes: El gen D4 del receptor de la dopamina humana (DRD4) contiene una repetición en tándem de 48 pares de bases (pb) en el tercer exón y muestra alelos que varían entre 2 y 11 repeticiones. El gen muestra un elevado nivel de expresión en el córtex pre-frontal del cerebro y se ha señalado la asociación de alelos particulares de este locus con varios trastornos neuro-psiquiátricos y de la personalidad.

Objetivo: El presente estudio informa sobre la distribución de frecuencias alélicas en el polimorfismo de repetición en tándem de número variable (VNTR) del locus DRD4, en cinco poblaciones étnicas de la India. Esta información es fundamental en el campo de la farmacogenética para los estudios sobre susceptibilidad a enfermedades y de asociación.

Sujetos y métodos: Se tiparon 332 individuos adultos sanos, no emparentados, procedentes de cinco grupos étnicos, los Konkanastha, Brahmins, Marathas, Ezhavas, Nairs y Musulmanes. El ADN genómico, extraído de sangre periférica, se amplificó mediante PCR utilizando un sistema bi-enzimático. Se comprobó que el uso del secuenciador de ADN ALF?Express era útil para genotipar poblaciones a gran escala. Los análisis estadísticos se realizaron utilizando los programas POPGENE y DISPAN.

Resultados: Se observó un total de ocho alelos que oscilaban entre 2 y 9 repeticiones. El alelo 4 fue el predominante en las cinco poblaciones, lo que era consistente con los datos de otras poblaciones del mundo. Se detectó un alelo 9 raro exclusivamente entre los Marathas. La heterozigosidad observada era baja, oscilando entre 0,38 y 0,54, mientras otros parámetros como el Contenido de Información Polimórfica (Polymorphic Information Content) y el Poder de Discriminación (Power of Discrimination) mostraron valores moderados. Las poblaciones estaban en equilibrio genético cuando se las testó bajo las condiciones de Hardy-Weinberg.

Conclusión: Las estimaciones de las frecuencias alélicas para el gen DRD4 proporcionadas en este estudio, contribuirán al desarrollo de una base de datos informativa sobre este locus funcionalmente relevante. Esto será útil cuando se estudie la asociación entre los factores genéticos y la patogénesis de la enfermedad en poblaciones indias, y para tratar la inquietud por los resultados sesgados de asociación debidos a las mezclas de población.     

中国汉族人群IL-1RA基因多态性及其与宫颈癌的相关性研究

目的 研究位于白细胞介素1受体拮抗剂基因（interleukin-1 receptor antagonist, IL-1RA）第二个内含子中可变串连重复序列（variable number of tandem repeats, VNTR）多态性在中国3个汉族人群中的分布情况,并探讨其与宫颈癌的发生关系。方法 采用PCR方法分别对3个汉族人群206例个体以及42例宫颈癌患者和45例对照进行多态性检测,扩增产物进行2％的琼脂糖电泳。结果 三个汉族群体的基因型以A1/A1和A1/A2最为常见。等位基因以A1频率最高,A2次之,群体间的差异是不显著的（P＞0.05）。与美、英高加索人群相比,A1 的频率明显偏高,A2明显偏低,而与非洲黑人相近。在宫颈癌患者和正常对照人群中,该多态位点的等位基因和基因型频率均无统计学意义（P＞0.05）。结论 IL-1RA第二个内含子中 VNTR多态性在不同种族间的分布存在着明显的差异,但与中国东北地区宫颈癌的发生可能无直接相关性。     

Characterization of a VNTR polymorphism in the coding region of the CEL gene

Human carboxyl ester lipase (CEL) secreted by the pancreas into the duodenum is a glycoprotein playing an essential role in the intestinal processing of cholesterol and lipid-soluble vitamins. The gene encoding CEL was known to contain a tandemly repeated sequence of the 11-amino-acid motif in the C-terminal region. We characterized its polymorphic features and found that there are five different alleles in Japanese populations and six in Caucasians. The allele containing 16 repeats is the most common in both populations. Although the distribution of the alleles seemed to be different in the two populations, the difference was not statistically significant. This polymorphism may influence the function of this enzyme and be a useful genetic marker to study diseases associated with cholesterol absorption. Received: December 26, 2001 / Accepted: January 30, 2002     

中国南方汉族和苗族人群hPARP1基因遗传多态性

目的检测人类聚腺苷二磷酸核糖聚合酶1[poly（ADP-ribose）polymerase 1，PARP1]基因的基因型和基因频率在中国南方汉族和苗族人群中的分布。方法收集187名中国南方汉族和210名苗族人的血液DNA，用PCR法扩增hPARP1基因4个外显子，并进行单链构象多态性分析。结果用PCR成功扩增出第12、13、16、17外显子，片段长度分别为253bp、313bp、175bp、362bp，在187名中国南方汉族和210名苗族人群中，分别有3人和9人检测出hPARP1基因第12、13、16和17外显子上各有1种基因突变，分别为Phe548Ser、Ala683Ser、Asp798Tyr、His808Arg。结论中国南方汉族和苗族人群中hPARP1基因第12、13、16和17外显子上存在突变型等位基因。