BACKGROUND & AIMS: :Tumor necrosis factor superfamily member 4 (TNFSF4) plays a key role in the process of atherosclerosis, a common risk factor for both myocardial and cerebral infarctions. Recent studies indicate that the single nucleotide polymorphism (SNP) rs3850641 in TNFSF4 is associated with higher risk of myocardial infarction, but little is known about the association between TNFSF4 variation and cerebral infarction (CI). A case-control study involving 385 CI patients and 385 age-matched, sex-matched non-CI controls was conducted in a Chinese population, only the most common subtype, atherosclerosis CI, was recruited. Two SNPs of TNFSF4, rs3850641 and rs3861950, were genotyped by the TaqMan SNP genotyping method, and verified partly by genomic DNA sequencing. The results revealed a significant allelic association between rs3861950 and CI (Odds ration = 1.733, 95 % confidence interval = 1.333-2.254, P = 0.000). Genotypic association analysis demonstrated that the CC genotype of rs3861950 confers susceptibility to CI (Odds ration = 2.896, 95 % confidence interval = 1.368-6.132), and it was associated with a significantly higher risk of ischemic stroke (Odds ration = 3.520, 95 % confidence interval = 1.546-8.015, P = 0.003) after adjusting for the other confirmed risk factors such as the history of hypertension, diabetes, CAD, smoking and alcohol drinking. While the odds ratio of the T allele to the C allele was 1.733 (95 % confidence interval: 1.333-2.254). However, there was no significant association between rs3850641 and CI (Odds ration = 1.288, 95 % confidence interval = 0.993-1.670, P = 0.056). TNFSF4 gene polymorphism rs3861950, but not rs3850641, is associated with the risk of atherosclerosis CI in a Chinese population.

背景与目标： : 肿瘤坏死因子超家族成员4 (TNFSF4) 在动脉粥样硬化过程中起关键作用，动脉粥样硬化是心肌和脑梗塞的常见危险因素。最近的研究表明，TNFSF4中的单核苷酸多态性 (SNP) rs3850641与心肌梗死的高风险相关，但对TNFSF4变异与脑梗死 (CI) 之间的关系知之甚少。在中国人群中进行了385例CI患者和385年龄匹配，性别匹配的非CI对照的病例对照研究，仅招募了最常见的亚型动脉粥样硬化CI。TNFSF4的两个SNP，rs3850641和rs3861950，通过TaqMan SNP基因分型方法进行了基因分型，并通过基因组DNA测序进行了部分验证。结果显示rs3861950和CI之间存在显着的等位基因关联 (赔率 = 1.733，95% 置信区间 = 1.333-2.254，P = 0.000)。基因型关联分析表明，rs3861950的CC基因型赋予CI易感性 (赔率 = 2.896，95% 置信区间 = 1.368-6.132)，并且与缺血性中风的风险显着增加相关 (赔率 = 3.520，95% 置信区间 = 1.546-8.015，P = 0.003) 在调整其他已确认的危险因素 (例如高血压，糖尿病，CAD，吸烟和饮酒史) 后。而T等位基因与C等位基因的比值比为1.733 (95% 置信区间: 1.333-2.254)。然而，rs3850641与CI之间没有显着关联 (赔率 = 1.288，95% 置信区间 = 0.993-1.670，P = 0.056)。TNFSF4基因多态性rs3861950 (而非rs3850641) 与中国人群动脉粥样硬化CI的风险相关。

BACKGROUND & AIMS: OBJECTIVE:Statins reduce inflammation and risk of myocardial infarction (MI). Because the myeloid IgA Fc receptor encoded by FCAR mediates inflammation, we hypothesized that the FCAR Asp92Asn polymorphism is associated with risk of MI and that this risk would be modified by pravastatin. METHODS AND RESULTS:In the placebo arm of the Cholesterol and Recurrent Events (CARE) study, male carriers of the 92Asn allele had an adjusted hazard ratio for incident MI of 1.68 (95% CI 1.10 to 2.57); relative risk reduction by pravastatin was 69% in carriers and 12% in noncarriers (P(interaction)=0.007). In the placebo arm of the all-male West of Scotland Coronary Prevention Study (WOSCOPS), carriers had an adjusted odds ratio for incident coronary heart disease (CHD) of 1.46 (90% CI 1.05 to 2.03); for pravastatin compared with placebo treatment, the adjusted odds ratios were 0.55 (95% CI 0.32 to 0.93) in carriers and 0.65 (95% CI 0.51 to 0.83) in noncarriers (P(interaction)=0.55). CONCLUSIONS:Carriers of 92Asn had increased risk of MI in CARE and increased odds of CHD in WOSCOPS. Pravastatin significantly reduced risk in carriers in both CARE and WOSCOPS. A genotype by treatment interaction was observed in CARE but not in WOSCOPS.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:Genetic susceptibility to inflammatory bowel disease is well recognized. There is also increasing evidence for the activation of the mucosal immune system and the production of inflammatory cytokines, i.e., interleukin (IL)-1ra and IL-1beta in the inflammatory bowel disease. The aim of this study was to analyze the IL-1beta and IL-1ra gene polymorphism and linkage disequilibrium coefficient between the different alleles of these genes in patients with Crohn's disease (CD) or ulcerative colitis (UC), according to the severity of the disease.

METHODS:Two hundred twenty-eight inflammatory bowel disease patients (87 UC and 141 CD) were included in this study and compared with 113 unrelated controls. The IL-1beta and IL-1ra gene polymorphism was studied after specific amplification of variable regions by PCR. A penta-allelic polymorphism, corresponding to a VNTR region located in intron 2 of the IL-1ra gene, was analyzed, whereas bi-allelic RFLPs displayed by two restriction enzymes (TaqI and AvaI) at position -511 of the IL-1beta gene were analyzed.

RESULTS:There was no significant difference of genotype distribution between controls and CD or UC patients. However, surgically treated UC patients were characterized by a higher frequency of genotype IL-1ra 1-2 (39 vs 16%, pc < 0.01) compared with nonoperated UC patients. Moreover, nonoperated UC patients displayed a lower frequency of IL-1ra allele 2 than surgically treated UC patients (14 vs 34%, pc < 0.002) or controls (14 vs 30%, pc < 0.005). Furthermore, simultaneous analysis of the IL-1beta and IL-1ra genes that are located in the same region of chromosome 2 revealed that CD patients carrying the IL-1beta allele 2 were more often noncarriers of IL-1ra allele 2 (p < 0.005). Moreover, UC and CD patients were, characterized by a lower frequency of the association of IL-1ra allele 2 and IL-1beta allele 2 compared with controls (8.3 vs 20.3% and 10.6 vs 20.3%, p < 0.03).

CONCLUSIONS:IL-1ra and IL-1beta gene polymorphism analysis from a clinical standpoint might help in defining UC prognosis. However, functional studies at both the circulating and mucosal level with stratification on allele associations, especially IL-1ra allele 2-IL-1beta allele 2 subgroups must be realized before therapeutic implications.

背景与目标： 目的 : 炎症性肠病的遗传易感性已广为人知。也有越来越多的证据表明粘膜免疫系统的激活和炎性细胞因子的产生，即炎症性肠病中的白介素 (IL)-1ra和IL-1beta。本研究的目的是分析克罗恩病 (CD) 或溃疡性结肠炎 (UC) 患者中这些基因的不同等位基因之间的IL-1beta和IL-1ra基因多态性以及连锁不平衡系数。根据疾病的严重程度。
方法 : 本研究纳入了28例炎症性肠病患者 (87 UC和141 CD)，并与113例无关的对照进行了比较。通过PCR对可变区进行特异性扩增后，研究了IL-1beta和IL-1ra基因多态性。分析了五等位基因多态性，对应于位于IL-1ra基因内含子2中的VNTR区域，而分析了IL-1beta基因511位的两种限制酶 (TaqI和AvaI) 显示的双等位基因rflp。
结果 : 基因型分布在对照组和CD或UC患者之间没有显着差异。然而，与非手术UC患者相比，手术治疗的UC患者的特征是基因型IL-1ra 1-2的频率更高 (39 vs 16%，pc <0.01)。此外，与手术治疗的UC患者 (14 vs 34%，pc <0.002) 或对照 (14 vs 30%，pc <0.005) 相比，非手术UC患者显示出较低的IL-1ra等位基因2频率。此外，对位于2号染色体相同区域的IL-1beta和IL-1ra基因的同时分析表明，携带IL-1beta等位基因2的CD患者更经常是IL-1ra等位基因2的非携带者 (p <0.005)。此外，UC和CD患者的特征是与对照组相比，IL-1ra等位基因2和IL-1beta等位基因2的关联频率较低 (8.3 vs 20.3% 和10.6 vs 20.3%，p <0.03)。
结论 : 从临床角度来看，IL-1ra和IL-1beta基因多态性分析可能有助于确定UC预后。但是，必须在循环和粘膜水平上进行功能研究，并对等位基因关联进行分层，尤其是IL-1ra等位基因2-IL-1beta等位基因2亚组进行分层，然后才能产生治疗意义。

BACKGROUND & AIMS: :Li-Fraumeni syndrome (LFS) is an autosomal-dominant cancer predisposition syndrome of which the majority is caused by TP53 germline mutations and is characterised by different tumour types occurring at relatively young age. Recently, it was shown that a single-nucleotide polymorphism (SNP) in the MDM2 gene, SNP309 (T>G variation), was associated with accelerated tumour formation in LFS patients who carry a TP53 germline mutation. To confirm this finding in different populations, we screened 25 Dutch and 11 Finnish TP53 mutation carriers for the presence of the SNP309 G allele in the MDM2 gene. Additionally, we investigated whether the SNP309 G allele plays a role in 72 Dutch TP53-negative LFS and LFS-related patients. In the TP53 germline mutation carriers, a significant difference was seen in the mean age of tumour onset for the SNP309 G allele group, that is, 29.7 years as compared to the SNP309 homozygous T group 45.5 years (P=0.005). In patients of LFS and LFS-related TP53-negative families, no difference was seen in the mean age of tumour onset. However, this TP53-negative group did show a significantly higher percentage of SNP309 homozygotes (G/G) compared to the general population (P=0.02). In conclusion, TP53 germline mutation carriers who have an SNP309 G allele have an earlier onset of tumour formation. The higher prevalence of MDM2 SNP309 homozygous G/G carriers in the TP53-negative group suggests that this allele contributes to cancer susceptibility in LFS and LFS-related families.

背景与目标： : Li-Fraumeni综合征 (LFS) 是一种常染色体显性癌症易感性综合征，其中大多数是由TP53种系突变引起的，其特征是在相对年轻的时候发生的不同肿瘤类型。最近，研究表明，MDM2基因SNP309 (T>G变异) 中的单核苷酸多态性 (SNP) 与携带TP53种系突变的LFS患者的肿瘤加速形成有关。为了在不同人群中证实这一发现，我们筛选了25个荷兰和11个芬兰TP53突变携带者，以寻找MDM2基因中snp309g等位基因的存在。此外，我们调查了SNP309 G等位基因是否在72名荷兰TP53-negative LFS和LFS相关患者中起作用。在TP53种系突变携带者中，与SNP309纯合T组相比，SNP309 G等位基因组的平均肿瘤发病年龄存在显着差异，即29.7岁 (P = 0.005)。在LFS和LFS相关TP53-negative家族的患者中，肿瘤平均发病年龄没有差异。然而，与普通人群相比，该TP53-negative组确实显示出明显更高的SNP309纯合子百分比 (G/G) (P = 0.02)。总之，具有snp309g等位基因的TP53种系突变携带者的肿瘤形成较早。TP53-negative组中MDM2 SNP309纯合G/G携带者的患病率较高，这表明该等位基因有助于LFS和LFS相关家庭的癌症易感性。

BACKGROUND & AIMS: OBJECTIVES:A broad range of phenytoin doses is used in clinical practice, with the final 'maintenance' dose normally determined by trial and error. A common functional polymorphism in the SCN1A gene (one of the genes encoding the drug target) has been previously associated with maximum dose of phenytoin used clinically, and also maximum dose of carbamazepine, another antiepileptic drug with the same drug target. METHODS:We have related variation at the SCN1A IVS5-91 G>A polymorphism to maximum dose and to maintenance dose of phenytoin in 168 patients with epilepsy treated with phenytoin. We also related genotype to phenytoin serum levels at maximum dose and at maintenance dose of phenytoin. We genotyped the polymorphism using an Applied Biosystems Taqman assay. RESULTS:The polymorphism is associated with phenytoin serum concentration at maintenance dose (P=0.03). In a reduced cohort of 71 patients receiving phenytoin monotherapy this association is also significant (P=0.03). Neither association remains significant after Bonferroni correction for multiple testing. CONCLUSIONS:These results are not a replication of the original study. They do, however, support the hypothesis that this polymorphism influences the clinical use of phenytoin. They also demonstrate the utility of using multiple phenotypes in pharmacogenetics studies, particularly when attempting to separate pharmacokinetic and pharmacodynamic effects. As the SCN1A polymorphism affects phenytoin pharmacodynamics, it is particularly useful to obtain data on serum levels in addition to dose because association of a pharmacodynamic variant may be stronger with serum levels than dose as the serum level may eliminate or reduce pharmacokinetic variability.

背景与目标：

BACKGROUND & AIMS: :We examined the extent of variation of the 3' region of the circumsporozoite gene among Plasmodium falciparum isolates through amplification of a selected DNA fragment followed by DNA sequencing. A total of 32 isolates were analyzed, of which 24 were from Amazon endemic areas in Brazil and 8 from widely separated geographical regions in the world. Among Brazilian isolates only 2 variants were detected: 19 displayed the same sequence of strain 7G8 whereas the 4 remaining isolates differed from the 7G8 strain at five nucleotide positions which also led to amino acid changes. Variation was restricted to one of the T-helper epitopes while the sequence identified as a cytotoxic T cell epitope was conserved in all Brazilian isolates. P. falciparum samples from other geographical regions in the world showed sequences distinct from those of Brazilian isolates. However, some constancy could be observed within that variation. For instance, the most frequent nucleotide substitutions, from A and C at nucleotide positions 1015 and 1024, were the same in all isolates.

背景与目标： : 我们通过扩增选定的DNA片段，然后进行DNA测序，检查了恶性疟原虫分离株中环子孢子基因3' 区域的变异程度。共分析了32个分离株，其中24个来自巴西的亚马逊流行地区，8个来自世界上广泛分离的地理区域。在巴西分离株中，仅检测到2个变体: 19个显示了相同的7G8菌株序列，而其余4个分离株在五个核苷酸位置与7G8菌株不同，这也导致了氨基酸变化。变异仅限于T辅助表位之一，而在所有巴西分离株中，被鉴定为细胞毒性T细胞表位的序列都是保守的。来自世界其他地理区域的恶性疟原虫样品显示出与巴西分离株不同的序列。但是，在该变化中可以观察到一些恒定性。例如，在所有分离物中，来自核苷酸位置1015和1024处的A和C的最频繁的核苷酸取代是相同的。

BACKGROUND & AIMS: OBJECTIVE:To investigate phenotypic consequences of renin gene polymorphism between Lyon hypertensive (LH) and normotensive (LN) rats because previously we demonstrated cosegregation of the LH allele with increased blood pressure in a cross of LH with LN rats.

DESIGN:Two studies were conducted. Study 1 used a cohort of male F2 rats from a LH x LN cross. Eighty-two rats homozygous for the hypertensive (HH) renin gene allele were compared with 82 rats homozygous for the normotensive (NN) allele. Urinary steroid excretion was measured in 24 h urine samples collected from rats aged 6 weeks. The direct aortic blood pressure was recorded in 30-week-old rats and, after they had been killed, their kidney renin concentration (KRC) was measured. In study 2, renin, angiotensinogen and angiotensin converting enzyme plasma concentrations and renin messenger RNA (mRNA) levels were measured in renal and extra-renal tissues from 6- and 25-week-old LH and LN parental and HH and NN F2 male rats.

METHODS:Urinary steroids and plasma components of the renin-angiotensin system (RAS) were measured using specific radioimmunoassays. mRNA levels were quantified by northern blotting.

RESULTS:In study 1, HH F2 rats had a higher blood pressure (151.5 +/- 8.2 versus 146.0 +/- 7.4 mmHg, P < 0.001) and a lower KRC (514 +/- 203 versus 666 +/- 304 micrograms A1/h per g cortex, P < 0.01) than did NN rats aged 30 weeks. In covariate analysis the decrease in KRC in HH rats was attributable to their increased blood pressure rather than to the renin genotype. The renin genotype of rats aged 6 weeks was not associated with a change in the urinary excretion of aldosterone, desoxycorticosterone, corticosterone or 18-hydroxy desoxycorticosterone. In study 2, we found no difference either in plasma levels of RAS components or in renal or extrarenal renin mRNA levels either between parental LH and LN rats or between HH and NN F2 rats apart from a higher plasma renin concentration in LH rats aged 6 weeks. Renal, but not extra-renal, renin mRNA levels declined with age.

CONCLUSIONS:We found no evidence of a renin genotype-dependent phenotypic difference in the RAS that could account for the effect of the renin locus on blood pressure in Lyon rats. Our findings suggest that the effect of the locus on blood pressure might be due to an as yet unidentified gene linked to renin.

背景与目标： 目标 : 为了研究里昂高血压 (LH) 和正常血压 (LN) 大鼠之间肾素基因多态性的表型后果，因为以前我们证明了LH等位基因与LN大鼠杂交中血压升高的共分离。
设计 : 进行了两项研究。研究1使用了来自LH x LN杂交的雄性F2大鼠队列。将82只高血压 (HH) 肾素基因等位基因纯合的大鼠与82只正常血压 (NN) 等位基因纯合的大鼠进行了比较。在从6周龄大鼠收集的24小时尿液样本中测量了尿类固醇排泄。在30周龄的大鼠中记录了直接的主动脉血压，并在杀死它们后测量了它们的肾脏肾素浓度 (KRC)。在研究2中，肾素，在6周和25周龄的LH和LN亲本以及HH和NN F2雄性大鼠的肾和肾外组织中测量了血管紧张素原和血管紧张素转换酶的血浆浓度以及肾素信使RNA (mRNA) 水平。
方法 : 使用特定的放射免疫测定法测量肾素-血管紧张素系统 (RAS) 的尿类固醇和血浆成分。通过northern印迹法定量mRNA水平。
结果 : 在研究1中，HH F2大鼠的血压较高 (151.5/- 8.2与146.0/- 7.4 mmHg，P <0.001) 和低于30周龄NN大鼠的KRC (514 +/- 203对666 +/- 304微克A1/h/g皮质，P <0.01)。在协变量分析中，HH大鼠的KRC降低归因于其血压升高，而不是肾素基因型。6周龄大鼠的肾素基因型与醛固酮，脱氧皮质酮，皮质酮或18-羟基脱氧皮质酮的尿排泄变化无关。在研究2中，我们发现父母LH和LN大鼠之间或HH和NN F2大鼠之间的RAS成分血浆水平或肾脏或肾外肾素mRNA水平没有差异，除了LH大鼠中较高的血浆肾素浓度外6周。肾素mRNA水平随着年龄的增长而下降，但肾素mRNA水平却没有下降。
结论 : 我们没有发现RAS中肾素基因型依赖性表型差异的证据，可以解释肾素基因座对里昂大鼠血压的影响。我们的发现表明，该基因座对血压的影响可能是由于与肾素相关的尚未鉴定的基因所致。

BACKGROUND & AIMS: :The human multidrug resistance gene (MDR1) encodes for P-glycoprotein (P-gp) which is a transmembrane transporter protein that acts as an efflux pump for a number of lypophilic compounds. It plays a protective role for cells against DNA damage. The wobble C3435T polymorphism at exon 26 has been associated with different expression levels and activity. Differences in allele frequency of the C3435T polymorphism have been demonstrated between distinct ethnic groups. In our study we examined these polymorphisms in 433 healthy individuals. From these, 229 were Central American mestizos from Nicaragua (n = 117) and El Salvador (n = 112) to be compared with a group of 204 North Spaniards, with the aim of detecting potential genotypic differences between these populations. The genotypes were determined by PCR-RFLP. The frequencies of the C allele were very similar among Central Americans (0.53) and Spaniards (0.52), which is consistent with the ethnic origin of Central American individuals (Amerindians and European Caucasians). In comparison to other previously studied populations, the C allele frequency in Central Americans was significantly lower than that found in African populations and higher than that observed in the Indian and Southwest Asian populations. These data may be relevant for dose recommendation of P-gp substrate drugs and also for studies of allele disease association in the Central American population.

背景与目标： : 人类多药耐药基因 (MDR1) 编码P-糖蛋白 (P-gp)，P-糖蛋白是一种跨膜转运蛋白，可作为许多嗜酸性化合物的外排泵。它对细胞免受DNA损伤起保护作用。外显子26的摆动C3435T多态性与不同的表达水平和活性有关。已在不同种族之间证明了C3435T多态性的等位基因频率差异。在我们的研究中，我们在433健康个体中检查了这些多态性。从这些229中，将尼加拉瓜 (n = 117) 和萨尔瓦多 (n = 112) 的中美洲混血儿与一组204的北西班牙人进行比较，目的是检测这些人群之间的潜在基因型差异。通过pcr-rflp确定基因型。C等位基因的频率在中美洲 (0.53) 和西班牙人 (0.52) 之间非常相似，这与中美洲个体 (美洲印第安人和欧洲高加索人) 的种族起源一致。与其他先前研究的人群相比，中美洲人的C等位基因频率明显低于非洲人群，高于印度和西南亚人群。这些数据可能与P-gp底物药物的剂量推荐有关，也与中美洲人群的等位基因疾病关联研究有关。

BACKGROUND & AIMS: :The clinical heterogeneity of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) with trisomy 8 as the sole abnormality may result from cytogenetically undetectable genetic changes. The purpose of this study was to identify hidden genomic aberrations not detected by metaphase cytogenetics (MC) using high-resolution single nucleotide polymorphism array (SNP-A)-based karyotyping in AML/MDS patients with a sole trisomy 8. The study group included 8 patients (3 AML and 5 MDS) and array-based karyotyping was done using whole-genome SNP-A (SNP 6.0 and SNP 2.7M). By SNP-A, additional genomic aberrations not detected by MC were identified in 2 patients: 1 AML patient exhibited a copy-neutral loss of heterozygosity (CN-LOH) of 3q21.1-q29 and 11q13.1-q25 and the other patient with MDS (refractory cytopenia with unilineage dysplasia) had CN-LOH of 2p25.3-p15. In particular, the latter patient progressed to AML 18 months after the diagnosis. In 3 patients, aberrations in addition to trisomy 8 were not identified by SNP-A. In the remaining 3 patients, SNP-A could not detect trisomy 8, while trisomy 8 was found in 25-67% of metaphase cells by MC. This study suggests that additional genomic aberrations may in fact be present even in cases of trisomy 8 as sole abnormality by MC, and SNP-A could be a useful karyotyping tool to identify hidden aberrations such as CN-LOH.

背景与目标： : 以8三体为唯一异常的急性髓性白血病 (AML) 或骨髓增生异常综合征 (MDS) 患者的临床异质性可能是由于细胞遗传学上无法检测到的遗传变化所致。这项研究的目的是使用高分辨率的基于单核苷酸多态性阵列 (snp-a) 的核型分析来鉴定中期细胞遗传学 (MC) 未检测到的隐藏的基因组畸变。研究组包括8例患者 (3例AML和5例MDS)，使用全基因组SNP-A (SNP 6.0和SNP 2.7M) 进行基于阵列的核型分析。通过SNP-A，在2例患者中发现了MC未检测到的其他基因组畸变: 1例AML患者表现出3q21.1-q29和11q13.1-q25的拷贝中性杂合性缺失 (cn-loh)，另一例MDS患者 (难治性血细胞减少症伴单膜发育不良) 的cn-loh为2p25.3-p15。特别是，后者在诊断后18个月进展为AML。在3例患者中，SNP-A未发现除8三体外的畸变。在其余3例患者中，SNP-A不能检测到8三体，而MC在25-67% 的中期细胞中发现8三体。这项研究表明，即使在MC唯一异常的8三体病例中，实际上也可能存在其他基因组畸变，SNP-A可能是识别隐藏畸变 (例如CN-LOH) 的有用核型分析工具。

BACKGROUND & AIMS: OBJECTIVE:The aim of the study was to explore the possible role of the 5-HT2A -1438G/A polymorphism in the susceptibility to anorexia nervosa (AN) in the Chinese Han population. METHODS:The -1438G/A polymorphism of 249 female AN patients, 228 matched healthy controls, and 198 trios was genotyped using SNaP shot assay. Psychopathological traits of eating-disordered behaviors in AN subjects were examined using the Chinese version of the Eating Disorder Examination Questionnaire. RESULTS:Neither the case-control analysis nor the transmission disequilibrium test revealed significant associations between the -1438G/A polymorphism and AN (P > .05). However, AA homozygote patients with AN had lower weight and shape concern scores of the EDE-Q6.0 than those of GA heterozygotes (P < .05). DISCUSSION:Our findings suggested that female AN patients with 5-HT2A -1438AA genotype may be characterized by less severe eating-disordered psychopathological traits in the Chinese Han population.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:The IDH1 gene, which encodes isocitrate dehydrogenase 1, is frequently mutated in gliomas and acute myeloid leukemia. The single-nucleotide polymorphism (SNP) (reference SNP no. rs11554137:C>T) located on IDH1 codon 105 has been associated with a poor outcome in patients with acute myeloid leukemia but has not been investigated in patients with gliomas. METHODS:The IDH1 codon 105 SNP was genotyped first in a series of 952 patients with grade 2 through 4 gliomas and was correlated with outcomes and tumor genomic profile. Then, it was genotyped in 2 validations sets of 306 patients with glioblastoma (GBM) and 591 patients with glioma. RESULTS:The minor allele codon 105 glycine (GGT) SNP (IDH1(105GGT) ) was identified in 98 of 952 patients (10.3%) and was not associated with the codon 132 (IDH1(132) ) mutation. Patients who had GMB with the IDH1(105GGT) variant had a poorer outcome than patients without the variant (median overall survival [OS], 10.7 months vs 15.5 months; P = .001; median progression-free survival [PFS], 6.4 months vs 8.5 months; P = .003). The prognostic impact was confirmed in an independent validation set of 306 GBMs from the same center (median PFS, 6.8 months vs 9.7 months; P = .006; median OS, 13.9 months vs 18.8 months; P = .0187). In the second validation cohort (591 grade 2-4 gliomas), a significant association was observed between IDH1(105GGT) and an adverse prognosis for the overall series and for patients with World Health Organization grade 3 gliomas, but the difference did not reach significance in patients with GBM. CONCLUSIONS:Taken together, the current data strongly suggested an association between the SNP rs11554137:C>T polymorphism and adverse outcomes in patients with malignant glioma. A single-nucleotide polymorphism (SNP) located on codon 105 of the isocitrate dehydrogenase 1 (IDH1) gene (reference SNP rs11554137) is analyzed in 3 independent series of patients with gliomas. The SNP rs11554137 is independent of the occurrence of somatic mutation on IDH1 codon 132, but, per se, has a prognostic impact in malignant gliomas.

背景与目标：

BACKGROUND & AIMS: :HepG2 and Huh7 cell lines are frequently used as models to study viral hepatitis and hepatocellular carcinoma. However, they exhibit significantly different capacities in their ability to support hepatitis B virus (HBV) replication. To investigate the basis for this, transcription factor-binding motifs at the HBV core promoter (HBVCP) were tested in luciferase reporter constructs to identify the possible role of host factors. Among the transcription factors screened: PARP1, SP1, HNF4α, HNF3, hB1F and HNF1, deletion of the PARP1 binding motif abrogated transcriptional activity at the HBVCP in HepG2 but not Huh7 cells. Sequencing of the PARP1 gene revealed that HepG2 cells carried an Ala762 allele which has low ADP-ribosylation activity, which was shown to have increased PARP1 binding affinity to its cognate motif thus resulting in higher transcriptional activity. PARP1 inhibitors that are being developed as broad cancer therapeutics also target PARP1 ADP-ribosylation enzymatic function. Four PARP1 inhibitors: PJ-34, ABT888, AZD2281 and AG014699 were tested for their effect on HBV replication. All four small molecules effectively enhanced HBV replication in vitro, confirming the role of PARP1 in HBV replication and that alteration of ADP-ribosylation by mutation or drugs can affect HBV replication. Our data demonstrate that natural polymorphisms in the host affecting proteins such as PARP1 can have a significant effect on HBV replication. Hence, patients who are infected with HBV and are on clinical trials involving PARP1 inhibitors may be at risk from unintended side-effects such as exacerbation of HBV replication.

背景与目标： : HepG2和Huh7细胞系经常用作研究病毒性肝炎和肝细胞癌的模型。然而，它们在支持乙型肝炎病毒 (HBV) 复制的能力方面表现出明显不同的能力。为了研究这一点的基础，在荧光素酶报告构建体中测试了HBV核心启动子 (HBVCP) 的转录因子结合基序，以确定宿主因子的可能作用。在筛选的转录因子中: PARP1，SP1，HNF4α，HNF3，hB1F和HNF1，PARP1结合基序的缺失消除了HepG2中HBVCP的转录活性，而不是Huh7细胞。PARP1基因的测序表明，HepG2细胞携带Ala762等位基因，该等位基因具有较低的ADP-核糖基化活性，这被证明具有增加的PARP1与其同源基序的结合亲和力，从而导致更高的转录活性。作为广泛的癌症治疗药物正在开发的PARP1抑制剂也针对PARP1 ADP-核糖基化酶功能。测试了四种PARP1抑制剂: PJ-34，ABT888，AZD2281和AG014699对HBV复制的影响。所有四个小分子在体外有效地增强了HBV复制，证实了PARP1在HBV复制中的作用，并且通过突变或药物改变ADP-核糖基化可以影响HBV复制。我们的数据表明，宿主中影响蛋白 (如PARP1) 的自然多态性对HBV复制有显著影响。因此，感染HBV并正在进行涉及PARP1抑制剂的临床试验的患者可能会受到意外副作用 (例如HBV复制恶化) 的风险。

BACKGROUND & AIMS: :Several genetic polymorphisms in metabolic activation or detoxification enzymes have been associated with susceptibility to therapy-related leukemia and myelodysplastic leukemia (TRLIMDS). We analyzed gene polymorphisms of NAD(P)H:quinone oxidoreductase (NQOl), glutathione S-tranferase (GST)-MI and -TI, and CYP3A4, the enzymes of which are capable of metabolizing anticancer drugs, in 58 patients with TRL/MDS and in 411 patients with de novo acute myeloid leukemia (AML). Homozygous Ser/Ser genotype of NQOl at codon 187, causing loss of function, was more frequent in the patients with TRLIMDS (14 of 58, 24.1%; OR = 2.62) than in those with de novo AML (64 of 411, 15.6%), and control (16 of 150, 10.6%; P = 0.002). Allelic frequencies of NQOJ were different between TRL/ MDS and de novo AML (P = 0.01). In GST-MJ and -Ti, the incidence of homologous deletion was similar among the three groups. The polymorphism of the 5' promoter region of CYP3A4 was not found in persons of Japanese ethnicity. These results suggest that the NQOJ polymorphism is significantly associated with the genetic risk of TRLIMDS.

背景与目标： : 代谢激活或解毒酶中的几种遗传多态性与治疗相关的白血病和骨髓增生异常性白血病 (TRLIMDS) 的易感性有关。我们分析了NAD(P)H: 醌氧化还原酶 (NQOl)，谷胱甘肽S-转移酶 (GST)-MI和-TI和CYP3A4的基因多态性，这些酶能够代谢抗癌药物，58例TRL/MDS患者和411例从头急性髓细胞白血病 (AML) 患者。NQOl密码子187的纯合Ser/Ser基因型导致功能丧失，TRLIMDS患者 (58例中的14例，24.1% 例; OR = 2.62例) 比从头AML患者 (411例中的64例，15.6% 例) 和对照组 (150例中的16例，10.6% 例) 更常见; P = 0.002)。在TRL/ MDS和从头AML之间，NQOJ的等位基因频率不同 (P = 0.01)。在GST-MJ和-Ti中，三组之间同源缺失的发生率相似。在日本人中未发现CYP3A4的5' 启动子区域的多态性。这些结果表明，NQOJ多态性与trimds的遗传风险显着相关。

BACKGROUND & AIMS: :The toll-like receptor 2 (TLR2) has gained importance as a major mammalian receptor for lipoproteins derived from the cell wall of a variety of bacteria, such as Borrelia burgdorferi, Treponema pallidum, and Mycoplasma fermentans. We were interested in identifying mutations in the TLR2 gene that might prove to be associated with altered susceptibility to septic shock. We performed a mutation screen of the TLR2 gene using single-stranded conformational polymorphism in 110 normal, healthy study subjects and detected an Arg753Gln mutation in three individuals. No other missense mutations were detected in the TLR2 open reading frame. Functional studies demonstrate that the Arg753Gln polymorphism, in comparison to the wild-type TLR2 gene, is significantly less responsive to bacterial peptides derived from B. burgdorferi and T. pallidum. In a septic shock population, the Arg753Gln TLR2 polymorphism occurred in 2 out of 91 septic patients. More importantly, both of the subjects with the TLR2 Arg753Gln polymorphism had staphylococcal infections. These findings suggest that a mutation in the TLR2 gene may predispose individuals to life-threatening bacterial infections.

背景与目标： : toll样受体2 (TLR2) 已成为哺乳动物主要的脂蛋白受体，其衍生自多种细菌的细胞壁，例如伯氏疏螺旋体，梅毒螺旋体和发酵支原体。我们对鉴定TLR2基因突变感兴趣，这些突变可能被证明与败血性休克易感性的改变有关。我们在110名正常，健康的研究对象中使用单链构象多态性对TLR2基因进行了突变筛选，并在三个个体中检测到Arg753Gln突变。在TLR2开放阅读框中未检测到其他错义突变。功能研究表明，与野生型TLR2基因相比，Arg753Gln多态性对源自B. burgdorferi和T. pallidum的细菌肽的反应明显降低。在败血性休克人群中，91例败血症患者中有2例发生了Arg753Gln TLR2多态性。更重要的是，具有TLR2 Arg753Gln多态性的两个受试者均患有葡萄球菌感染。这些发现表明，TLR2基因的突变可能使个体容易受到威胁生命的细菌感染。

BACKGROUND & AIMS: :A small cryptic Lactobacillus helveticus plasmid, pLBL4, was able to reveal restriction fragment length polymorphism in different bacterial species including Lactobacillus species, Bacillus species, and Escherichia coli when used as a DNA probe. The observed polymorphism was a result of the combined hybridization of several microsatellite sequences. The 6-bp sequence (TTGTTT) was repeated 12 times, seven of which were concentrated within the region between 1791 and 1997 bp of the plasmid sequence. The polymorphic patterns generated with pLBL4 differed from those obtained with M13 DNA in the larger number of bands observed. The results presented here open the possibility of using pLBL4 as a new broad-spectrum polymorphic DNA probe for fingerprint analysis.

背景与目标： : 当用作DNA探针时，一个小的隐秘螺旋乳杆菌质粒pLBL4能够揭示不同细菌物种 (包括乳杆菌物种，芽孢杆菌物种和大肠杆菌) 中的限制性片段长度多态性。观察到的多态性是几个微卫星序列联合杂交的结果。将6-bp序列 (TTGTTT) 重复12次，其中7次集中在质粒序列的1791至1997 bp之间的区域内。在观察到的大量条带中，pLBL4生成的多态性模式与M13 DNA获得的多态性模式不同。此处介绍的结果为使用pLBL4作为新的广谱多态性DNA探针进行指纹分析提供了可能性。