No evidence of association between structural polymorphism at the dopamine D3 receptor locus and alcoholism in the Japanese

Dopaminergic systems mediate reward mechanisms and are involved in reinforcing self-administration of dependence-forming substances, including alcohol. Studies have reported that polymorphisms of the dopamine D2 receptor, whose structure and function are similar to those of the dopamine D3 receptor, increase the susceptibility to alcoholism. These observations led to the examination of the possible association between a structural polymorphism of the D3 receptor gene and alcoholism. Genotyping results, employing a PCR-RFLP method, showed no difference in allele and genotype frequencies of the D3 BalI polymorphism (Ser⁹/Gly⁹) between Japanese alcoholics and controls. Moreover, these frequencies were not altered in alcoholics with inactive aldehyde dehydrogenase-2 (ALDH2), a well-defined negative risk factor for alcoholism. These results strongly suggest that the dopamine D3 receptor is not associated with alcoholism. © 1996 Wiley-Liss, Inc.     

No association between neutrophil FcgammaRIIa allelic polymorphism and anti-neutrophil cytoplasmic antibody (ANCA)-positive systemic vasculitis.

ANCA, implicated as having a pathogenic role in systemic vasculitis, can activate tumour necrosis factor-alpha (TNF-alpha)-primed neutrophils by cross-linking surface-expressed ANCA antigens with neutrophil FcgammaRIIa receptors to release reactive oxygen species. The FcgammaRIIa receptor exists as polymorphic variants, R131 and H131, which differ in their ability to ligate human IgG2 and IgG3. Neutrophils homozygous for the FcgammaRIIa-H131 allotype bind more efficiently to IgG3 than the FcgammaRIIa-R131 allotype and are the only human FcgammaR which bind IgG2. Our aim was to determine whether the homozygous FcgammaRIIa-H131 individuals are more susceptible to developing ANCA-associated systemic vasculitis and nephritis due to differential IgG binding and activation. FcgammaRIIa allotype was determined by both allele-specific polymerase chain reaction (PCR) and Southern blotting with allele-specific oligonucleotide probes end-labelled with 32P-gammaATP, after PCR amplification of genomic FcgammaRIIa DNA in 107 Caucasian patients with ANCA+ vasculitis (of whom 89 had renal disease) and 100 ethnically matched controls. Phenotyping of neutrophil FcgammaRIIa alleles was confirmed in some patients by quantitative flow cytometry using murine MoAbs 41H16 and IV.3. Of the patients with ANCA+ systemic vasculitis, 75 had ANCA with specificity for proteinase 3 and 32 with specificity for myeloperoxidase. Overall, no skewing in FcgammaRIIa allotypes was seen in patients compared with controls. No significant increase of the FcgammaRIIa-H131 allotype was found amongst patients irrespective of ANCA specificity, and no association between the FcgammaRIIa allotype and nephritis was found. Our data suggest that the FcgammaRIIa receptor allotype is not a major factor predisposing to the development of ANCA+ systemic vasculitis, or to nephritis.     

儿茶酚-O-甲基转移酶Vall58Met和汉族精神分裂症的关联/连锁分析

目的：探讨儿茶酚－Ｏ－甲基转移酶（ＣＯＭＴ）第１５８位密码子从缬氨酸到蛋氨酸的错义突变（Ｖａｌｌ５８Ｍｅｔ）多态性与精神分裂症的关系。方法：在４２个至少包含２名符合ＩＣＤ－１０精神分裂症诊断标准的患病同胞、父母存活的汉族家系中,对ＣＯＭＴＶａｌｌ５８Ｍｅｔ多态标记进行检测。结果：１）ＣＯＭＴ等位基因频度和基因型频度在父母组、非患病同胞组和患病同胞组之间无差异,在三组男女性别之间以及在精神分裂症不     

Lack of association between atopy and RsaI polymorphism within intron 2 of the PcεRI-β gene in a Spanish population sample

Background The B genotype of RasI polymorphism located within intron 2 of the Fc-lgE receptor I (Fc.Rl) gene was previously found to be increased in atopic patients from a Japanese population sample.
Methods We studied these A/B genotypes in 70 Spanish atopic patients, and the results were compared to those of 51 nonatopic controls. RasI polymorphisms were studied by specific digestion of polymerase chain reaction fragments followed by polyacrylamide gel electrophoresis. Results The polymorphism frequency (A/A: 25/70, A/B: 28/70, B/B: 17/70) found in patients did not differ from the frequency in nonatopic control subjects.
Conclusions We did not find RasI polymorphisms associated with atopic disease. The genetic findings in atopy and asthma may be very different according to ethnic and local characteristics, and they must be carefully verified in difFerent population samples.     

Association between early onset and organ manifestations of systemic lupus erythematosus (SLE) and a down-regulating promoter polymorphism in the MBL2 gene

The serum concentration of mannose-binding lectin (MBL) is genetically determined by a series of allelic polymorphisms in the MBL2 gene. Since several polymorphisms of the MBL2 gene have been suggested to be risk locus for systemic lupus erythematosus (SLE), we investigated MBL2 polymorphisms in 315 SLE patients from Hungary and 182 geographically matched healthy controls. Within the group of patients, we found that homozygotes for an MBL2 down-regulating promoter polymorphism at position -221 (YA to XA) (rs7096206) were significantly (p=0.017) younger at diagnosis than the other patients. The frequency of juvenile-onset SLE (相似文献   

DICER and DROSHA gene expression and polymorphisms in autoimmune thyroid diseases

Dicer and Drosha are RNase III enzymes that are necessary for the biogenesis of most miRNAs. However, there are no reports on the association of Dicer and Drosha with the pathogenesis of autoimmune thyroid disease (AITD). We genotyped DICER rs3742330A/G and rs1057035T/C as well as DROSHA rs644236C/T and rs10719C/T polymorphisms in 255?Hashimoto's disease (HD) patients, in 255 Graves' disease (GD) patients and in 128 healthy controls by the polymerase chain reaction (PCR)- restriction fragment length polymorphism (RFLP) method. We also examined the expression of DICER and DROSHA gene in peripheral blood mononuclear cells (PBMCs) by quantitative RT-PCR (qRT-PCR) methods. The TT genotype of the DICER rs1057035 polymorphism was less frequent in GD patients (p?=?0.0098) than in healthy subjects. The CC genotype of DROSHA rs644236 polymorphism were more frequent in GD patients than in HD patients (p?=?0.0171). The gene expression of DICER was lower in patients with AITD compared with that in control subjects (p?=?0.0064) and was lower in patients with GD in remission than in patients with intractable GD (p?=?0.0213). In addition, the expression of DROSHA was lower in patients with AITD than that in control subjects (p?p?=?0.0440). In conclusion, the DICER rs1057035 TT genotype and DROSHA rs644236?CC genotype were associated with the development of GD and the differentiation between GD and HD, respectively. The expression levels of DICER and DROSHA genes were low in AITD and differed depending on the intractability of GD and the severity of HD, respectively.     

Association of tumor necrosis factor receptor 2 (TNFR2) polymorphism with susceptibility to systemic lupus erythematosus

Multiple genetic as well as environmental factors are considered to be involved in the development of systemic lupus erythematosus (SLE). A number of previous studies have suggested a possible role for tumor necrosis factor (TNF) in the pathogenesis of SLE. In addition, one of the candidate loci suggested by the genome-wide linkage analysis corresponds to the chromosomal position encompassing the TNF receptor 2 gene (TNFR2). The purpose of this study was to analyze the polymorphism of TNFR2 and its possible association with the susceptibility to SLE, using the case-control association analysis. Polymorphism screening of the exons containing previously reported nonsynonymous base substitutions was carried out by the polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) method, using genomic DNA from 81 Japanese patients with SLE and 207 healthy individuals. Two alleles were present in exon 6, coding for methionine (196M) and arginine (196R) at position 196. 30 of 81 patients (37.0%) with SLE were positive for the 196R allele, which was significantly more frequent compared with 39 of 207 healthy individuals (18.8%) (chi2=10.6, df=l, P=0.001, odds ratio=2.53, 95% CI: 1.45-4.43). Genotype analysis revealed that the presence of one 196R allele was sufficient for rendering susceptibility. The association of 196R allele with SLE was independent from that of HLA-DRB1*1501. In conclusion, the TNFR2 196R allele was found to be significantly associated with the susceptibility to SLE in the Japanese population. Further population and functional studies will be of particular importance to establish TNFR2 as one of the susceptibility genes to SLE.     

注意缺陷多动障碍与儿茶酚-O-甲基转移酶基因Val158Met多态性的关联分析

目的探讨注意缺陷多动障碍(attention-deficit hyperactivity disorder,ADHD)汉族患儿与儿茶酚-O-甲基转移酶(catechol-O-methyltransferase,COMT)基因第158位密码子G→A点突变所引起的缬氨酸→甲硫氨酸(Val158Met)的错义突变多态性的关系.方法采用聚合酶链反应-限制性片段长度多态性技术,分析了117例符合DSM-Ⅳ诊断标准的上海汉族ADHD患儿与105例正常健康对照组的COMT基因的Val158Met多态性位点频率.结果 ADHD组的A等位基因频率为25.21%,而对照组为23.81%,两组差异无显著性(χ2=0.5197, P＞0.05). COMT各基因型的分布频率在ADHD和对照组之间的差异也无显著性(P＞0.05).结论汉族儿童注意缺陷多动障碍COMT基因Val158Met多态性可能与ADHD无关联.     

Arg753Gln polymorphism of the human Toll-like receptor 2 gene from infection to disease in pediatric tuberculosis

The aim of this study is to examine the occurrence of the Arg753Gln polymorphism of the Toll-like receptor 2 (TLR2) gene in Turkish children with pulmonary and/or extrapulmonary tuberculosis (TB) disease compared with that in healthy children with latent TB infection (LTBI) and to assess the risk of progression from LTBI to active TB disease in children. The Arg753Gln polymorphism of the TLR2 gene was studied in 198 TB patients compared with 200 ethnically and age-matched children with LTBI. The culture confirmed TB patients were more frequently Arg753Gln heterozygous [odds ratio (OR) 5.05, 95% confidence interval (95% CI) 2.61-9.76, p = 0.00], and Gln allele frequency was significantly higher in the patient group (13.86% vs 3.5%, OR 4.40, 95% CI 2.34-8.30, p = 0.00). We also showed that the frequencies of the heterozygous Arg753Gln genotype and the Gln allele were significantly higher in patients with pulmonary TB alone and in patients with definitive pulmonary plus extrapulmonary TB than in children with LTBI. Our data suggest that the Arg753Gln polymorphism of the TLR-2 gene influences the speed of progression from infection to TB disease in children. Further investigations are needed to clarify whether this polymorphism has a strong impact on susceptibility to TB in children.     

Lack of association of serotonin‐2A receptor gene polymorphism (T102C) with suicidal ideation and suicide

Serotonergic dysfunction has been implicated in the pathophysiology of affective disorders and suicidality. Especially the density of the 5‐HT2A receptor was claimed as being increased in suicidality, proposed as an adaptive upregulation due to reduced serotonergic transmission. Recent studies have shown an association of allele C of the 5‐HT2A‐T102C polymorphism with suicidal ideation in patients with major depression. The purpose of this study was to test whether this proposed marker indicates susceptibility not only to suicidal ideation in depressed patients but also to suicidality as a syndrome. We investigated the 5‐HT2A‐T102C polymorphism in 131 suicide victims with unknown underlying psychiatric diagnoses, 84 patients with major depression with or without suicidal ideation, and 125 healthy controls. We were unable to find any association of genotype or allele frequencies to major depression, suicidal ideation, or suicide as a syndrome. Thus, our results suggest that this polymorphism may not commonly be involved in the susceptibility to suicidality. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:831–835, 2000. © 2000 Wiley‐Liss, Inc.     

Polymorphisms and expression of genes encoding Argonautes 1 and 2 in autoimmune thyroid diseases

The microRNA (miRNA) biogenesis pathway is regulated by specific proteins and enzymes, including Dicer, Drosha, DGCR8, Exportin 5 and the Argonaute (AGO) family. In this study, we investigated the AGO family, which is the primary component of RISC (RNA-induced silencing complex) and directly binds to microRNA. We examined the association of polymorphisms in AGO family genes with AGO expression and with the development and prognosis of autoimmune thyroid diseases. We genotyped AGO1 rs636832A/G, AGO2 rs7005286C/T, AGO2 rs11166985A/G and AGO2 rs2292779C/G polymorphisms in 184 Graves’ disease (GD) patients, 195 Hashimoto’s disease (HD) patients and 122 healthy volunteers using the polymerase chain reaction-restriction fragment length polymorphism method. We also examined the expression of AGO1 and AGO2 mRNAs in peripheral blood mononuclear cells (PBMC) obtained from 52 GD patients, 41?HD patients, and 25 healthy volunteers using quantitative RT-PCR methods. The G allele of AGO1 rs636832 and the A allele of AGO2 rs11166985 polymorphisms were significantly more frequent in GD patients than in healthy controls. The A allele of AGO2 rs11166985 was also significantly more frequent in intractable GD patients than in controls. The C carrier (CC?+?CG genotypes) and C allele of AGO2 rs2292779 polymorphism were significantly more frequent in intractable GD patients than in patients with GD in remission. Expression of AGO1 mRNA in PBMC was significantly higher in AITD patient than in controls, and that of AGO2 mRNA in PBMC was significantly higher in intractable GD patients than in patients with GD in remission. Furthermore, the expression levels of both the AGO1 and AGO2 genes were significantly correlated with the proportions of Th17 cells in PBMC. In conclusion, the polymorphisms of the AGO1 and AGO2 genes, the expression levels of which correlated with the proportion of Th17 cells, were associated with the development and prognosis of GD. The AGO2 rs2292779 C carrier and C allele were associated with the intractability of GD.     

Lack of association between CTLA-4 gene polymorphism and IDDM in Japanese subjects

Susceptibility to insulin-dependent diabetes mellitus (IDDM) is determined by both environmental and genetic factors. The main gene associated with predisposition to IDDM is HLA. Recent studies have described linkage and association of IDDM to the CTLA-4 gene (IDDM12) in Caucasians. CTLA-4 is a candidate gene for T-cell-mediated autoimmune diseases because it is a negative regulator of T-cell proliferation. We investigated the distribution of a CTLA-4 gene polymorphism in 110 Japanese patients with IDDM and 200 control subjects. In 84 patients, we also investigated associations between this CTLA-4 gene polymorphism and GAD65 antibody positivity. An A/G transition at position 49 of exon 1 was analyzed by the polymerase chain reaction-restriction fragment length polymorphism method. GAD65 antibody was detected using a radioligand binding assay. There was no significant difference in the distribution of CTLA-4 alleles in patients and controls and no difference was observed in prevalence of CTLA-4 alleles when GAD65 antibody-positive and -negative individuals in the IDDM groups were compared. The present study did not support an association between the CTLA-4 gene and IDDM in the Japanese population.     

α2-巨球蛋白基因I1000V多态性与散发阿尔茨海默氏病的关联研究

目的近年来有研究发现α2-巨球蛋白基因(α2-macroglobulin，A2M)Ile1000Val多态与阿尔茨海默氏病(Alzheimer’s disease，AD)发病有关联，但也有相悖的研究结果报道。因此．我们利用较大的样本，观察了A2M基因Ile1000Val多态在广州及成都地区汉族老年人中的分布，并探讨其与散发AD的相关性。方法以广州地区257例散发AD患者和242名正常老年人、成都地区112例散发AD患者和113名正常老年人为对象进行病例一对照研究。用聚合酶链反应一限制性片段长度多态性方法分析A2M基因11000V多态性和载脂蛋白E基因(apolipoprotelnE，apoE)多态性。结果(1)在两地合并样本中，AD患者与对照组中等位基因A2M-1000V的频率分别为7．7％与8．7％，广州与成都地区AD患者与对照组中A2M基因I1000V多态的分布差异无统计学意义。(2)散发AD无论按是否伴有apoE—ε4或按发病年龄分成不同亚组后，A2M基因I1000V多态的分布在病例组与对照组之间差异无统计学意义。结论广州与成都汉族人群中A2M基因I1000V多态与散发AD不具有关联。     

Lack of association between TaqI A1 allele of dopamine D2 receptor gene and alcohol-use disorders in Atayal natives of Taiwan

Association studies between the A1 allele of the dopamine D2 receptor (DRD2) gene TaqI A polymorphism and alcoholism remain controversial. A recent study from Japan demonstrated that the A1 allele is associated with severe alcoholism in the Japanese population. We were interested in knowing if this association also exists in the Atayals of Taiwan, who were found to have a higher prevalence of alcohol-use disorders than the Han Chinese in Taiwan. Genotype and allele frequencies were determined in alcohol-abusing, alcohol-dependent, and nonalcoholic control Atayal natives in Taiwan. A1 allele frequencies in alcohol-dependent, alcohol-abusing, and normal control Atayals were 0.39, 0.42, and 0.39, respectively. No difference in A1 allele frequency was found among these three groups. Our data do not support the hypothesis that the A1 allele of the TaqI A polymorphism of the DRD2 gene increases susceptibility to alcohol-use disorders in the Atayals of Taiwan. © 1996 Wiley-Liss, Inc.     

Lack of association between NRAMP1 gene polymorphisms and Trypanosoma cruzi infection

Genetic analysis in mice and humans have established the key role of the human natural resistance-associated macrophage protein 1 (NRAMP1) in resistance to intracellular infections. In the present study we investigated whether four NRAMP1 polymorphisms (5'(GT)n, -236 C-->T, D543N, and 3'UTR deletion) were important in determining the susceptibility to Trypanosoma cruzi infections as well as in the development of chagasic cardiac disease. Genotyping for these variants was assessed in 83 seropositive (asymptomatic, n=51, cardiomyopathic, n=32) and 85 seronegative individuals from a Peruvian population where T. cruzi is endemic. No statistically significant differences either between patients and controls or between asymptomatic and cardiomyopathic individuals were observed with respect to NRAMP1 variants. Our data suggest that the NRAMP1 genetic polymorphism analysed do not play a major role in the pathogenesis of T. cruzi infection in this Peruvian sample.     

Lack of association of the common TaqIB polymorphism in the cholesteryl ester transfer protein gene with angiographically assessed coronary atherosclerosis

The anti-atherogenic effect of cholesteryl ester transfer protein (CETP) genetic variants associated with lowered enzyme activity is controversial. Moreover, in a few studies, this effect has been evaluated in the presence of a certain risk factor constellation. We addressed this issue in a case-control study, where 415 subjects with angiographically documented coronary artery disease (CAD +), 397 subjects without CAD (in 215, CAD was excluded by coronarography (CAD-)), and 188 healthy population controls, were screened for the CETP TaqIB polymorphism. The prevalence of the low-activity TaqIB2 allele was 0.396 in CAD+, and 0.428 and 0.416 in CAD- and population controls, respectively (p = 0.40). Its presence was significantly associated with increased high-density lipoprotein cholesterol (HDL-C) in population controls (1.40 +/- 0.40 mmol/l in B1B1, 1.52 +/- 0.39 mmol/l in B1B2 and 1.58 + 0.46 mmol/l in B2B2; p < 0.03 for trend), but not in the other groups. The CETP TaqIB polymorphism accounted for < 1% of the HDL-C variance in the whole cohort (p = 0.048). After adjustment for other risk factors, the CETP TaqIB2 allele was found not to be associated with significant changes in CAD risk independently of an assumed either dominant (odds ratio (OR) 0.97; 95% confidence interval (CI) 0.66-1.44; p = 0.89) or recessive effect (OR 0.68; 95% CI 0.42-1.12; p = 0.13). The CETP TaqIB polymorphism did not show a significant interaction with other risk factors in influencing CAD risk. Our findings do not support the hypothesis that a genetic variant resulting in lowered CETP activity is associated with reduced risk of coronary atherosclerosis.     

Lack of association between the -2518G/A polymorphism of the MCP-1 gene and ischaemic heart disease: a family-based investigation

Using two recently described family-based tests of association, the possible role of the functional -2518G/A polymorphism in the promoter region of the monocyte chemoattractant protein-1 (MCP-1) gene in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population. One thousand and twelve individuals from 386 families with at least one member prematurely affected with IHD were genotyped for the MCP-1 -2518G/A polymorphism. Using the combined transmission disequilibrium test and the pedigree disequilibrium test, no association between the MCP-1 -2518G/A polymorphism and IHD was found. Our data demonstrate that, in an Irish population, the MCP-1 -2518G/A polymorphism is not strongly associated with IHD.     

The association between COX-2 gene rs5275 polymorphism and Nasopharyngeal carcinoma risk

The overexpression of cyclooxygenase-2 (COX-2) was correlated with the invasion and lymphatic metastasis and with the clinical stage of Nasopharyngeal carcinoma (NPC). The C allele of COX-2 gene rs5275 polymorphism disrupts miR-542-3p function to promote COX-2 overexpression. To examine the role of COX-2 gene rs5275 polymorphism in NPC, we determined COX-2 gene rs5275 polymorphism by using a custom-by-design 48-Plex single nucleotide polymorphism (SNP) Scan^? Kit. We found that C allele or CC genotype of rs5275 polymorphism in COX-2 gene was associated with an increased risk of NPC. In stratified analyses, COX-2 gene rs5275 polymorphism was associated with the risk of NPC among females, smokers, and drinkers. Based on these results, we concluded that COX-2 gene rs5275 variant contributes to NPC risk in a Chinese population. Larger studies with more diverse ethnic populations are needed to confirm these results.     

转化生长因子β2基因多态性与中国汉族先天性心脏病的关联研究

目的 探索转化生长因子β2(transforming growth factor β2,TGFβ2)基因上的一个标签单核苷酸多态性位点(rs6658835)与中国汉族人群先天性心脏病(congenital beart disease,CHD)的相关性.方法 用聚合酶链反应和限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)法检测324例常见先天性心脏病(房间隔缺损144例,动脉导管未闭88例,室间隔缺损92例)以及158名正常对照者TGFβ2基因rs6658835位点的单核苷酸多态性.结果 与正常对照相比,房间隔缺损患者、动脉导管未闭患者基因型及等位基因分布差异无统计学意义(P＞0.05),而室间隔缺损患者的基因型及等位基因分布与正常对照比较差异有统计学意义(P＜0.05).结论 rs6658835位点的单核苷酸多态性与室间隔缺损的易感性存在关联.