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。

BACKGROUND & AIMS: :Background: The association of the fetal MTHFR A1298C (rs1801131) polymorphism and neural tube defects (NTDs) susceptibility has been widely demonstrated, but the results remain inconclusive. Thus, we performed a meta-analysis to investigate the association between fetal MTHFR A1298C polymorphism and NTDs risk.Methods: An electronic search of PubMed, web of science, SciELO, CNKI database for studies on the fetal MTHFR A1298C polymorphism and NTDs risk was performed up to March 30, 2020.Results: A total of 22 case-control studies with 3,224 fetuses with NTDs and 3,295 controls were selected. Overall, pooled data showed that the fetal MTHFR A1298C polymorphism was not significantly associated with risk an increased risk of NTDs in the global population. When stratified analysis by ethnicity, country of origin and NTDs type, still no statistically significant association was found.Conclusions: Our pooled data emerged no evidence for significant association between fetal MTHFR A1298C polymorphism and NTDs risk.

背景与目标： 背景: 胎儿MTHFR A1298C (rs1801131) 多态性与神经管缺陷 (NTDs) 易感性的关联已被广泛证明，但结果尚无定论。因此，我们进行了荟萃分析，以调查胎儿MTHFR A1298C多态性与NTDs风险之间的关系。方法: 对PubMed，web of science，SciELO，CNKI数据库进行了2020年3月30日的胎儿MTHFR A1298C多态性与NTDs风险研究。结果: 总共选择了22例病例对照研究，其中3,224例具有NTDs的胎儿和3,295例对照。总体而言，汇总数据显示，胎儿MTHFR A1298C多态性与全球人群中NTDs风险增加的风险没有显着相关性。当按种族，原籍国和NTDs类型进行分层分析时，仍然没有发现统计学上的显着关联。结论: 我们的汇总数据没有证据表明胎儿MTHFR A1298C多态性与NTDs风险之间存在显着关联。

BACKGROUND & AIMS: OBJECTIVE:Mild traumatic brain injuries (mTBIs) have frequently been associated with the emergence and persistence of depressive symptoms. However, the factors which contribute to the increased risk for depression after these head injuries remain unclear. Accordingly, we examined the relationship between frequency of self-reported mTBIs and current symptoms of depression and the mediating role of rumination and cognitive flexibility. We also examined whether these relations were moderated by sex differences and the presence of the Val66Met polymorphism in a gene coding for brain-derived neurotrophic factor (BDNF). DESIGN:Retrospective, cross-sectional. SETTING:Carleton University. PARTICIPANTS:Two hundred nineteen Carleton University undergraduate students. MAIN OUTCOME MEASURES:Cognitive flexibility as assessed by the Wisconsin Card Sorting Task (WCST); subtypes of rumination (Ruminative Response Scale; Treynor, Gonzalez, and Nolen-Hoeksema, 2003); depressive symptoms (Beck Depression Inventory; Beck, Ward, and Mendelson, 1961). RESULTS:Greater frequency of self-reported mTBIs was associated with more frequent depressive rumination among women, but not men, which was accompanied by elevated current depressive symptoms. In addition, among Met allele carriers of the BDNF polymorphism, but not those who were Val homozygotes, greater frequency of mTBIs was related to higher levels of brooding, which was accompanied by heightened depressive symptoms. Brain-derived neurotrophic factor genotype also moderated the relationship between self-reported mTBIs and cognitive flexibility in that more frequent mTBIs were associated with more perseverative errors on the WCST among Met carriers, but not Val homozygotes. CONCLUSIONS:The present findings raise the possibility that the evolution of depression after mTBIs may be dependant on a BDNF polymorphism and sex differences.

背景与目标：

BACKGROUND & AIMS: :TLR4 polymorphisms such as Asp299Gly and Thr399Ile related to Gram-negative sepsis have been reported to result in significantly blunted responsiveness to LPS. Our study group previously screened other TLR4 polymorphic variants by checking the NF-κB activation in comparison to wild type (WT) TLR4 in human embryonic kidney 293T cells. In this study, we found that the Lys694Arg (K694R) polymorphism reduced the activation of NF-κB, and the production of downstream inflammatory factors IL-1, TNF-α and IL-6, representing the K694R polymorphism, led to blunted responsiveness to LPS. Then, we examined the influence of the K694R polymorphism on total and cell-surface TLR4 expression by Western blotting and flow cytometry, respectively, but observed no differences between the K694R polymorphism and WT TLR4. We also used co-immunoprecipitation to determine the interaction of the K694R polymorphism and WT TLR4 with their co-receptor myeloid differentiation factor 2 (MD2) and their downstream signal adaptor MyD88. We found that K694R reduced the recruitment of MyD88 in TLR4 signalling but had no impact on the interaction with MD2.

背景与目标： : 据报道，与革兰氏阴性脓毒症相关的TLR4多态性 (如Asp299Gly和Thr399Ile) 导致对LPS的反应性明显减弱。我们的研究小组先前通过检查人胚肾293T细胞中与野生型 (WT) TLR4相比的NF-κ b活化来筛选其他TLR4多态性变体。在这项研究中，我们发现Lys694Arg (K694R) 多态性降低了NF-κ b的活化，并且代表K694R多态性的下游炎症因子IL-1，TNF-α 和IL-6的产生导致对LPS的反应性减弱。然后，我们分别通过蛋白质印迹和流式细胞术检查了K694R多态性对总TLR4和细胞表面TLR4表达的影响，但在K694R多态性和WT TLR4之间没有观察到差异。我们还使用共免疫沉淀来确定K694R多态性和WT TLR4与其共受体髓样分化因子2 (MD2) 及其下游信号衔接子myd88的相互作用。我们发现K694R减少了TLR4信号传导中MyD88的募集，但对与md2的相互作用没有影响。

BACKGROUND & AIMS: :The ability of viability selection to maintain single-locus polymorphism is investigated with two models in which the population is bombarded with a series of mutations with random fitnesses. In the first model, the population is allowed to reach equilibrium before mutation resumes; in the second the iterations and mutation occur simultaneously. Monte Carlo simulations of these models show that viability selection is easily able to maintain stable 6- or 7-allele polymorphisms and that monomorphisms and diallelic polymorphisms are uncommon. The question of how monomorphisms arise is also discussed.

背景与目标： : 通过两个模型研究了生存能力选择维持单基因座多态性的能力，在两个模型中，种群被一系列具有随机适应性的突变轰击。在第一个模型中，允许种群在突变恢复之前达到平衡; 在第二个模型中，迭代和突变同时发生。这些模型的蒙特卡洛模拟表明，生存力选择很容易维持稳定的6或7等位基因多态性，并且单态和双等位基因多态性并不常见。还讨论了单态如何产生的问题。

BACKGROUND & AIMS: :The methylenetetrahydrofolate reductase (MTHFR) may play a pathological role in polycystic ovary syndrome (PCOS). However, the conclusions of published reports on the relationship between the MTHFR C677T polymorphism and PCOS risk remain controversial.To derive a more precise estimation we performed a metaanalysis based on 22 studies that together included 2405 cases and 2419 controls. PubMed, EMBASE, WanFang and the Chinese National Knowledge Infrastructure databases were used to retrieve articles up to up to October 28, 2019. The crude odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated to evaluate the association.Metaanalysis results showed a significant association between the MTHFR C677T polymorphism and PCOS risk in 3 genetic models (allele model: OR = 1.40, 95% CI = 1.27-1.53; dominant model: OR = 1.47, 95% CI = 1.17-1.85); homozygous model: OR = 1.90, 95% CI = 1.55-2.32). Moreover, significant associations were observed when stratified by ethnicity, source of controls, etiology, and genotype methods.This metaanalysis suggests that the T-allele of the MTHFR C677T polymorphism is associated with an increased risk of PCOS, especially in Asians further studies with larger population sizes are needed to confirm these results.

背景与目标： : 亚甲基四氢叶酸还原酶 (MTHFR) 可能在多囊卵巢综合征 (PCOS) 中起病理作用。然而，关于MTHFR C677T多态性与PCOS风险之间关系的已发表报告的结论仍存在争议。为了得出更精确的估计，我们基于22项研究进行了荟萃分析，这些研究共包括2405例病例和2419例对照。PubMed，EMBASE，WanFang和中国国家知识基础设施数据库用于检索多达2019年10月28日的文章。计算95% 置信区间 (95% CI) 的粗优势比 (or) 来评估相关性。荟萃分析结果表明，MTHFR C677T多态性与3种遗传模型 (等位基因模型: or   =   1.40，95% CI   =   1.27-1.53; 显性模型: or   =   1.47，95% ci   =   1.17-1.85); 纯合模型: or   =   1.90，95% ci   =   1.55-2.32)。此外，当按种族，对照来源，病因和基因型方法分层时，观察到显着的关联。该荟萃分析表明，MTHFR C677T多态性的T等位基因与PCOS的风险增加有关，尤其是在亚洲人中，需要进一步的研究来证实这些结果。

BACKGROUND & AIMS: BACKGROUND:Some patients show warfarin resistance needing more than 70 mg of warfarin per week. In this study, we examined if C3435T polymorphism of MDR1 gene could be a factor of warfarin resistance. METHODS:We examined 196 blood specimens from the patients who took warfarin more than 42 mg/week for at least 1 year. The subjects consisted of 74 European Americans, 59 African Americans, 42 Hispanic Americans and 21 Asian Americans. Genotype of C3435T polymorphism was determined by using real-time polymerase chain reaction (PCR). RESULTS:Ninety (45.9%) of the 196 patients had C3435T genotype and the remaining patients had C3435C genotype (35.7%) and T3435T genotype (18.4%). Mean dose of warfarin of patients with C3435C, C3435T and T3435T genotypes were 59.5mg/week, 56.9 mg/week and 55.6 mg/week, respectively. There was no statistical difference in the dose of warfarin between the 3 genotypes within each race. CONCLUSION:Our results suggest that C3435T polymorphism of MDR1 gene is not associated with warfarin resistance.

背景与目标：

BACKGROUND & AIMS: BACKGROUND AND OBJECTIVE:A variety of cytokines are involved in the incidence and development of bronchial asthma. This study was designed to reveal the relationship among genetic polymorphism of cytokine genes, expression levels of cytokines and incidence of bronchial asthma. METHODS:We analyzed 14 single nucleotide polymorphism loci in the 10 major cytokine genes plus plasma protein levels of 7 proteins in the bronchial asthma patients (n = 108) and the healthy population (n = 88) of the Han people in northern China. The polymorphism-based genotypes were identified by the sequence-specific primer-polymerase chain reaction. The plasma protein levels were determined by enzyme-linked immunoassay. Bioinformatics analysis was applied to further data processing. RESULTS:Data presented here showed that the 6 polymorphism loci were significantly correlated with the incidence of asthma (p < 0.05). Two of them, IL-2 (-330) and IL-2 (+166), constituted a linkage disequilibrium block. The GG haplotype of this block gave a relatively higher correlation with asthma (p = 0.0767). The plasma protein levels of IgE, IL-6 and IL-1 beta correlated with a number of polymorphism loci tested (p < 0.05), of which IgE gave the most significant correlation. The plasma IL-10 and IL-12 levels of the patients in the asthma group were significantly lower than those of the healthy adults in the control group (p < 0.05), while IgE gave the opposite result (p < 0.0001). We constructed a prototype of the metabolic and regulatory network composed of bronchial asthma-related proteins. In this network, IL-6 and TNF-alpha, were found with a high degree (D = 343 and 235, respectively) and IL-1beta with a moderate degree of connection (D = 155). CONCLUSIONS:We have found that various degrees of correlation with cytokine genes and protein expression of single nucleotide polymorphism in bronchial asthma. IL-6 and IL-1beta appear to play important biological roles in the pathogenesis of asthma. During the analysis of correlation between genetic polymorphism and a complex disease, the effects of environmental factors should be taken into account. The information at the protein level should be fully developed and the bioinformatics techniques can be used for the comprehensive analysis, to have a deep understanding of molecular mechanisms of incidence and development of diseases.

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