Single nucleotide polymorphisms in VEGF gene are associated with an increased risk of osteosarcoma

We aimed to assess whether the five common SNPs can affect the risk of osteosarcoma, and its association with demographic characteristics of osteosarcoma. 165 osteosarcoma patients and 330 cancer-free controls were enrolled into our study. Five common SNPs in VEGF gene, -2578C/A (rs699947), -1156G/A (rs1570360), +1612G/A (rs10434), +936C/T (rs3025039) and -634G/C (rs2010963), were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Conditional logistic regression analyses found that individuals with AA genotype and A allele of rs699947 were associated with an increased risk of osteosarcoma. Individuals with GG genotype and G allele of rs2010963 were associated with an increased risk of osteosarcoma. By stratified analysis, AA genotype of rs699947 was associated with an increased risk of osteosarcoma in those with shorter age, males and a family history of cancer, and GG genotype of rs2010963 was correlated with an increased risk of osteosarcoma in those with shorter age, females and a family history of cancer. Our study suggests that rs699947 and rs2010963 polymorphisms may play a role in the pathogenesis of osteosarcoma.     

Association of ABCB1 and VEGFA gene polymorphisms with breast cancer susceptibility and prognosis

Breast cancer (BC) is the most common cause of cancer-related death in women worldwide. Several ABCB1 and VEGFA gene polymorphisms, such as ABCB1-G1199 T/A (rs2229109), VEGFA -634 G > C (rs2010963), VEGFA 2578 C > A (rs699947) and VEGFA 7 C > T (rs25648) have been associated with risk of BC and clinical outcomes. The purpose of this study was to evaluate the association between these gene polymorphisms and BC risk and prognosis.A retrospective case-control study was conducted, including 84 BC cases and 119 controls of Spanish (European, Caucasian) origin. ABCB1-G1199 T/A (rs2229109), VEGFA -634 G > C (rs2010963), VEGFA 2578 C > A (rs699947) and VEGFA 7 C > T (rs25648) gene polymorphisms were analysed by TaqMan®.The genotypic logistic regression model adjusted by aged revealed no association with any of the polymorphisms and BC risk, although the C-allele of VEGFA 2578 C > A showed a trend to higher BC risk in the allelic and recessive models (p = 0.055 and 0.054, respectively). There was no influence of these gene polymorphisms on overall survival (OS). The univariate Cox model showed that carriers of the A-allele for VEGFA 2578 C > A tended to have longer OS compared to CC patients (CC vs A-allele Hazard ratio (HR): 2.08; CI95 % = 0.96–4.49; p = 0.0587). There was no association between the gene polymorphisms analysed and disease-free survival (DFS). The univariate Cox model showed a trend toward a longer DFS in patients carrying ABCB1-G1199 T/A GG genotype compared to those with A-allele (GG vs A-allele HR: 0.43; CI95 % = 0.18–1.03; p = 0.0612).No influence of ABCB1-G1199 T/A (rs2229109), VEGFA -634 G > C (rs2010963), VEGFA 2578 C > A (rs699947) and VEGFA 7 C > T (rs25648) gene polymorphisms on risk of developing BC was found in our study. There was no association between the polymorphisms studied and DFS and OS.     

Association between the three functional miR-146a single-nucleotide polymorphisms,rs2910164, rs57095329, and rs2431697, and autoimmune disease susceptibility: A meta-analysis

Studies suggest associations between the miR-146a single nucleotide polymorphisms (SNPs) and susceptibility to autoimmune diseases. However, the results are inconsistent and inconclusive. Therefore, the aim of this study was to arrive at a conclusion about the association between the three functional miR-146a SNPs and autoimmune disease risk. Studies were identified through PubMed/MEDLINE searches for studies published up to January 2016 using as keywords rs2910164, rs57095329, rs2431697, and miR-146a polymorphisms. Thirty studies were included in the meta-analysis. The SNP rs2910164?G?>?C was found to be associated with increased risk of multiple sclerosis (CC?+?CG versus GG, OR = 1.25, 95% CI: 1.01–1.55), with decreased risks of psoriasis (C versus G, OR = 0.81, 95% CI: 0.69–0.96; CC versus GC?+?GG, OR = 0.73, 95% CI: 0.56–0.94), Behcet’s disease (CC versus GC?+?GG, OR = 0.60, 95% CI: 0.50–0.73), asthma (C versus G, OR = 0.80, 95% CI: 0.69–0.93; CC versus GC?+?GG, OR = 0.65, 95% CI: 0.48–0.86), and uveitis (CC?+?CG versus GG, OR = 0.61, 95% CI: 0.49–0.77). The SNP rs2431697 C?>?T was found to be associated with an increased risk of SLE (T versus C, OR = 1.26, 95% CI: 1.15–1.38; TC?+?TT versus CC, OR = 1.28, 95% CI: 1.03–1.58; TT versus TC?+?CC, OR = 1.40, 95% CI: 1.21–1.62). The SNP rs57095329 A?>?G was found to be associated with an increased risk of SLE (G versus C, OR = 1.25, 95% CI: 1.17–1.35). The miR-146a SNPs rs2910164, rs57095329, rs2431697 are associated with susceptibility to certain autoimmune diseases. However, for other autoimmune diseases, they may be protective or insignificant.     

Association of adiponectin polymorphism with cord blood adiponectin concentrations and intrauterine growth

To assess whether adiponectin gene (ADIPOQ) polymorphism is associated with intrauterine fetal growth and cord blood adiponectin, we investigated eight single-nucleotide polymorphisms (SNPs; rs182052, rs710445, rs16861205, rs12495941, rs1501299, rs3774261, rs2082940 and rs266729) in ADIPOQ and birth weight and cord blood adiponectin in 526 healthy neonates. We found that the neonates carrying the G allele of rs266729 had a significantly greater birth weight s.d. score than those homozygous for the C allele (CC: -0.06±0.75 versus CG: 0.20±0.64 versus GG: 0.07±0.78; P=1.65 × 10(-3), adjusted P=9.90 × 10(-3)). However, this difference was not significant after adjustment for cord blood adiponectin (P=0.04, adjusted P=0.26). The rs266729 SNP was strongly associated with cord blood adiponectin; neonates with rs266729 GG had the highest adiponectin (CC: 34.1±20.2 versus CG: 44.3±26.1 versus GG: 54.1±36.7?μg?ml(-1), P=2.80 × 10(-9), adjusted P=1.68 × 10(-8)). This association remained after adjustment for birth weight s.d. score (P=6.63 × 10(-8), adjusted P=3.98 × 10(-7)). Our results suggest that the influence of the rs266729 SNP in ADIPOQ on birth weight may be dependent on circulating adiponectin.     

云南省傣族、汉族人群乙型肝炎病毒感染与IL-6-572C/G和IFNAR1-168G/C的关联性研究

目的:探讨云南省西双版纳地区傣族和汉族人群IL-6-572C/G和I型干扰素受体1(interferon alpha receptor 1,IFNAR1)-168G/C位点单核苷酸多态性与乙型肝炎病毒(HBV)感染后疾病转归的关联性。方法:采集西双版纳州傣族、汉族人群血液样本共600份,其中每个民族包括健康对照组100名、HBV感染患者200名(含100名自限性恢复患者和100名慢性乙肝患者),运用限制性片段长度多态性聚合酶链反应(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)和DNA测序技术对IL-6-572C/G和IFNAR1-168G/C位点进行基因分型。结果:傣族人群中,-572C/G位点基因型多态性与HBV感染后转归的关联性并无统计学显著性。C、G等位基因型在HBV感染组、正常对照组之间和慢性乙肝组、自限恢复组之间差异无统计学显著性。但是在G显性模式(GG+CG/CC)下,GG+CG基因型为HBV感染者发展成为慢性乙型肝炎患者的保护因素(P0.05)。汉族人群中,-572C/G位点基因型和等位基因分布频率在各组比较中无统计学显著性,并且在G显性模式和G隐性模式比较中也无统计学显著性。在上述4种比较中,IFNAR1-168G/C位点在汉族和傣族样本中的差异均无统计学显著性。结论:IL-6-572C/G位点GG+CG基因型可能是傣族人群中HBV感染者发展成为慢性乙型肝炎的保护因素,而IFNAR1-168G/C多态性与HBV感染后转归在傣、汉两族中并无显著性关联。     

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

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

宁夏回、汉族群体LIN28B基因多态性

目的 探讨LIN28B基因rs314277和rs314276位点在宁夏地区回、汉族群体中及不同性别间的分布特征。方法 研究对象来自宁夏医科大学2011级健康学生共705例,其中男性回、汉族分别为144例和167例,女性回、汉族分别为188例和206例。SNPs分型均采用基因测序来检测。 结果 宁夏回族群体LIN28B基因两个多态位点基因型频率及等位基因频率分别为：男性rs314277 (AC:4.5%,CC:38.9%; A:2.3%, C:41.1%); rs314276(AA: 2.7%,AC:21.4%,CC:19.3%; A:13.4%,C:30.0%);女性rs314277(AA: 0.6%,AC:7.5%,CC:48.5%; A:4.4%, C:52.3%); rs314276(AA:3.3%,AC:28.9%,CC:24.4%;A:17.8%,C:38.9%);宁夏汉族群体LIN28B基因两个多态位点基因型频率及等位基因频率分别为：男性rs314277(AC:3.2%, CC:41.6%; A:1.6%, C:43.2%); rs314276(AA: 4.6%,AC:17.4%, CC:22.8%; A:13.3%, C:31.5%);女性rs314277(AC:4.6%, CC:50.7%; A:2.3%, C:52.9%); rs314276(AA: 4.8%,AC:18.8%,CC:31.6%; A:14.2%, C:41.0%)。 结论 宁夏人群LIN28B基因rs314277多态性位点等位基因频率在回、汉族之间差异有显著性(P<0.05);rs314276多态性位点基因型频率在回、汉族之间差异有显著性(P<0.05);LIN28B基因两个多态性位点在宁夏不同性别之间差异无显著性(P>0.05);宁夏人群两个多态性位点基因型和等位基因型频率的分布与人类基因组计划扫描所得不同种族人群相比差异有显著性(P<0.05)。     

Association between miRNA-146a rs2910164 (G/C) polymorphism with the susceptibility to chronic HBV infection and spontaneous viral clearance in an Iranian population

Hepatitis B virus (HBV) infection is one of the clinical dilemmas in chronic liver diseases. MicroRNAs (miRNAs) are small noncoding RNA molecules that play an important role in the pathogenesis of liver diseases and single nucleotide polymorphisms (SNPs) in miRNA genes affect the clinical course of HBV infection. Previous studies have shown that miRNA-146a rs2910164 polymorphism can be associated with the pathogenesis of liver diseases such as hepatocellular carcinoma. The present study investigated the association between miRNA-146a rs2910164 polymorphism and susceptibility to HBV infection in an Iranian population. The study comprised 266 patients with chronic HBV infection, 172 patients with spontaneous viral clearance (SVC) after acute HBV infection, and 266 healthy control adjusted for sex and age. The genotyping of the miRNA-146a rs2910164 polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our data revealed that GG genotype and G allele of miRNA-146a rs2910164 SNP is dominated (P < 0.001) in patients with chronic HBV infection (Odds ratio [OR] = 3.92; 95% confidence interval [CI] = 2.1-7.32). miRNA-146a rs2910164 polymorphism showed a statistically significant association (P < 0.001) between CC genotype and allele C with SVC (OR = 2.92; 95% CI = 1.56-546). Our findings suggest miRNA-146a SNP (C/G) in our population may be associated with the susceptibility to HBV infection and CC genotype is associated with SVC. Also, the GG genotype and G allele at miRNA-146a rs2910164 is associated with chronic HBV infection in our population.     

基因多态性与青海妊娠高血压疾病的相关性

目的 探讨内皮型一氧化氮合酶（eNOS）、肿瘤坏死超家族成员13B（TNFSF13B）、缺氧诱导因子 1α（HIF-1α）、血管内皮生长因子A（VEGFA）、血管内皮生长因子受体1（VEGFR1）的基因多态性与青海孕产妇HDCP易感性的相关性。 方法 采用病例对照研究,120例HDCP孕产妇为研究组,同期100例健康孕产妇为对照组,所有研究对象均来自青海省。使用Sequenom MassARRAY 法检测研究对象HIF-1α基因SNP位点 RS 11549465、RS 115494657和RS 2057482;TNFSF13B基因SNP位点RS 16972194;eNOS基因SNP位点RS 2070744;VEGFA基因SNP位点RS 3025029和RS 2010963;VEGFR1基因SNP位点RS 7335588、RS 722503和RS 12584067基因型分布,比较各SNP位点在两组间的差异。结果 eNOS基因、VEGFA基因和VEGFR1基因各SNP位点在两组之间差异有显著性(P<0.001或P<0.05）。位点RS 2070744和RS 3025039基因型CC在研究组的比例均高于对照组（均P<0.001）;其中,等位基因C在HDCP人群中发病风险度（OR）分别为:2.13（1.45～3.12）和4.95（2.97～8.26）（均P<0.001）。位点RS 2010963和RS 7335588基因型GG在研究组中比例均低于对照组（均P<0.05）;此两个位点等位基因G在HDCP人群中发病风险度（OR）分别为0.50（0.34～0.74）和0.46（0.30～0.72）（均P<0.001）。位点RS 722503基因型TC在研究组的比例为56.67％,高于对照组的29.00％;等位基因C在人群HDCP发病风险度为2.46（1.58～3.84）（P<0.001）。 结论 VEGFA、VEGFR1和eNOS的基因多态性与青海妊娠高血压疾病有一定的关联,是该病在青海发病率高的潜在遗传易感基因。     

Functional SNP in 3′‐UTR MicroRNA‐Binding Site of ZNF350 Confers Risk for Age‐Related Cataract

Many studies have suggested that individual susceptibility to age‐related cataract (ARC) may be associated with DNA sequence polymorphisms affecting gene regulation. As DNA repair is implicated in ARC pathogenesis and single‐nucleotide polymorphisms (SNPs) in the 3′‐terminal untranslated region (3′‐UTR) targeted by microRNAs (miRNAs) can alter the gene function, we hypothesize that the miRNA‐binding SNPs (miRSNPs) in DNA double‐strand break repair (DSBR) and nucleotide excision repair (NER) pathways might associate with ARC risk. We genotyped nine miRSNPs of eight genes in DSBR and NER pathways in Chinese population and found that ZNF350‐ rs2278414:G>A was significantly associated with ARC risk. Even though the Comet assay of cellular DNA damage indicated that all the subtypes of ARC patients had more DNA breaks in peripheral lymphocytes than the controls independent of rs2278414 genotypes, individuals carrying the variant A allele (AA and AG) had lower ZNF350 mRNA levels compared with individuals with GG genotype. Moreover, the in vitro experiment indicated that miR‐21‐3p and miR‐150‐5p specifically downregulated luciferase reporter expression in the cell lines transfected with rs2278414 A allele compared with rs2278414 G. These results suggested that the association of SNP rs2278414 with ARC might involve an altered miRNA regulation of ZNF350.     

Association of PD-L1 gene rs4143815 C>G polymorphism and human cancer susceptibility: A systematic review and meta-analysis

Programmed death ligand 1(PD-L1) mediated immune escape play important roles in the development of cancer. The gene polymorphism of PD-L1, in particular rs4143815 C?>?G, has been associated with the cancer risks, but with conflicting results. Therefore, this meta-analysis was aimed to assess the association between rs4143815 C?>?G and cancer susceptibility. A systematic literature search was performed to select the studies and the pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of association. Eleven eligible studies containing 3711 cases and 3704 controls were enrolled in the meta-analysis. The results suggested that there is a strong association between rs4143815 C?>?G and the cancer risks (G vs. C: OR?=?1.386, 95% CI: 1.132–1.696, p?=?0.002; GG vs. CG?+?CC: OR?=?1.843 95% CI: 1.300–2.613, p?=?0.002; GG?+?CG vs. CC: OR?=?1.280, 95% CI: 1.040–1.576, p?=?0.020). Subgroup analysis based on cancer type suggested that PD-L1 rs4143815 C?>?G might increase the susceptibility to gastric cancer (G vs. C: OR?=?1.842, 95% CI: 1.403–2.418, p?<?0.001) and bladder cancer (G vs. C: OR?=?2.015, 95% CI: 1.556–2.608, p?<?0.001), and genotype GG carriers of PD-L1 rs4143815 C?>?G might have higher risks of HCC (GG vs. CG?+?CC: OR?=?2.226 95% CI: 1.562–3.172, p?<?0.001). PD-L1 rs4143815 C?>?G might confer an increased cancer risk, indicating this SNP may contribute to the pathogenesis of cancer and might be used as a potential biomarker to predict the susceptibility to cancer.     

α2-Heremans-Schmid糖蛋白基因多态性与其血清含量的关联研究

目的 探讨α2-Heremans-Schmid糖蛋白(α2-Heremans-Schmid glycoprotein,AHSG)基因单核苷酸多态(single nucleotide polymorphism,SNP)与其血清含量的相关性及其参与调节基因转录的机制.方法 对AHSG基因进行重测序,构建连锁不平衡模式,选择标签SNP在192名北京汉族和424名广州汉族个体中进行了基因分型;应用报告基因荧光素酶活性检测不同等位基因的转录活性;应用酶联免疫吸附试验检测北京地区192名个体血清中AHSG的浓度.结果 AHSG重测序共检出8个SNP,连锁不平衡分析显示广州和北京地区人群的连锁不平衡模式不同,但选择的标签SNP和具有潜在功能的SNP的等位基因和基因型频率分布在两组人群中差异无统计学意义.荧光素酶活性实验结果显示,AHSG基因启动子区-799A等位基因比-799T等位基因的转录活性高;多态性位点rs2248690、rs4917和rs4918与血清中AHSG的含量存在相关性;多元回归分析结果表明只有rs2248690与AHSG含量存在相关性.结论 位于AHSG基因启动子区的rs2248690位点与其血清中含量存在相关性.     

广西人群IL-22基因多态性分布特征及其与血脂的关系

目的:研究广西正常人群中白细胞介素22(IL-22)基因rs2227485C/T和rs2227491A/G位点的多态性分布特点和在不同人群间的分布差异,探讨不同基因型间常见血脂指标水平的差异。方法:采取多重单碱基延伸法(SNa Pshot)和DNA测序相结合的方法对280例广西人群IL-22基因的rs2227485C/T和rs2227491A/G位点进行基因分型检测,并用统计学方法比较各组间多态性分布的差异及不同基因型间血脂指标水平的差异。结果:rs2227485C/T存在CC、CT和TT 3种基因型,分布频率分别为17.1%、49.3%和33.6%,此位点基因型及等位基因频率在广西人群不同性别间的差异无统计学显著性(P0.05),其基因型及等位基因与国际人类基因组单体型图计划公布的意大利、北京、日本和墨西哥人群相比,差异有统计学意义(P0.05);rs2227491A/G存在AA、AG和GG 3种基因型,分布频率分别为16.1%、52.8%和31.1%,此位点基因型及等位基因频率在广西人群不同性别间的差异无统计学显著性(P0.05),基因型频率与意大利、日本和墨西哥人群之间的差异有统计学意义(P0.05),等位基因分布频率与其他4个人群相比差异均有统计学意义(P0.05)。rs2227491A/G位点3种基因型间的HDL-C和LDL-C差异有统计学意义(P0.05),其中HDL-C在AG/AA与GG组比较差异有统计学意义(P0.05),LDL-C在AG/GG和AA组比较差异有统计学意义(P0.05)。结论:IL-22基因rs2227485C/T和rs2227491A/G位点多态性在不同人群间存在着差异。rs2227491A/G多态性与血脂水平相关。     

AXIN2基因三个位点与先天性巨结肠的关联研究

目的 探讨AXIN2基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)rs2240308、rs8081536和rs9913621 3个位点与先天性巨结肠(Hirschspnmg disease,HSCR)的关联性.方法 对120例HSCR患者和120名正常人群外周血进行基因组DNA抽提,用PCR技术对AXe2基因3个位点(rs2240308、rs8081536和rs9913621)进行PCR扩增,PCR产物用内切酶CviJ I、Dde I和BaN I消化,将SNPs位点进行分型与分析,应用X2检验统计分析病例组和对照组等位基因频率、等位基因型频率及其患病风险;同时将PCR产物进行测序,以进一步确定基因突变位点.结果 HSCR组与对照组AXIN2 rs8081536 CC和CT基因型频率差异无统计学意义(P＞0.05);而HSCR组与对照组AXIN2 rs2240308 GG、AG和从基因型频率及A和G等位基因频率差异有统计学意义(P＜0.05),GC和从基因型及G等位基因的患病风险分别为2.091、0.846和1.703;HSCR组与对照组AXIN2 rs9913621 CC、CT和TT基因型频率及C和T等位基因频率差异有统计学意义(P＜0.05),CC和TT基因型及T等位基因的患病风险分别为0.535、1.113和1.569.测序rs2240308第301位密码子核苷酸GCA→CCA杂合突变;rs913621第199位密码子核苷酸CAC→CAG杂合突变.结论 AXIN2 rs8081536等位基因变异与HSCR的易感性无关;AXIN2 rs2240308和rs9913621与HSCR的发生可能有关联,具有GG基因型与CC基因型患HSCR的危险性相对较高.     

Exploration of 16 candidate genes identifies the association of IDE with Alzheimer's disease in Han Chinese

Alzheimer's disease (AD) has a complex pattern of inheritance and many genes have recently been reported to contribute to the disease susceptibility. We selected 106 SNPs within 16 candidate genes and performed a multistage association study using 4 sample sets consisting of 731 AD patients and 738 control subjects to identify genetic factors for AD in Han Chinese. A single nucleotide polymorphism (SNP) in the insulin degrading enzyme gene (IDE), rs3781239, showed a significant association with AD. The C allele increased the risk of AD 1.72-fold than the G allele (odds ratio [OR] = 1.72, 95% confidence interval [CI] = 1.17-2.53, p = 0.006) and CC carriers had a 4.89-fold higher risk for AD than that of the carriers with CG and GG genotypes (odds ratio = 4.89, 95% CI = 1.85-12.91, p = 0.001). Moreover, the CC genotype was significantly associated with earlier age at onset (p = 0.001, hazard ratio [HR] = 2.09, 95% CI = 1.38-3.18). Our data suggest that the polymorphism of IDE is associated with susceptibility to Alzheimer's disease in Han Chinese.     

Association of RIP2 gene polymorphisms and systemic lupus erythematosus in a Chinese population

The aim of this study was to investigate the association of receptor interacting protein 2 (RIP2) single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. A case-control study was performed on the SNPs rs16900617 and rs16900627 in 590 Chinese SLE patients and 660 healthy controls. These SNPs were typed by TaqMan allele discrimination assays. We found a significant association of rs16900617 G allele [odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.41-0.72] and rs16900627 G allele (OR = 1.28, 95% CI 1.04-1.58) with SLE. Significant differences in genotype frequency distribution were also found in SLE and control individuals (rs16900617: AG versus AA, OR = 0.59, 95% CI 0.44-0.81; GG versus AA, OR = 0.08, 95% CI 0.01-0.65; AG + GG versus AA, OR = 0.55, 95% CI 0.41-0.75; rs16900627: AG versus AA, OR = 1.51, 95% CI 1.17-1.93; AG + GG versus AA, OR = 1.43, 95% CI 1.13-1.82). Analysis of the haplotypes revealed that two haplotypes of AG and GA were also significantly associated with SLE (OR = 1.37, 95% CI 1.11-1.70; OR = 0.60, 95% CI 0.45-0.79). Our findings suggest that the RIP2 gene polymorphisms may be associated with susceptibility to SLE in the Chinese population.     

Haplotype block 1 variant (HB-1v) of the NKG2 family of receptors

The natural killer group 2 (NKG2) family of receptors, encoded within the NK complex gene region (NKC), modulate the cytotoxic activity of NK cells. Two haplotype blocks throughout the NKC, hb-1 and hb-2 have been associated with different levels of overall natural cytotoxicity. Here, we evaluated allelic and genotype frequencies at rs1049174, rs2617160, rs2617170, rs2617171, rs1983526 (hb-1 haplotype), and rs2255336 and rs2246809 (hb-2 haplotype) in 928 subjects examined from Mexico City. The most frequent alleles and genotypes were as follows: C, CG to rs1049174; G, GG to rs2255336; T, AT to rs2617160; G, GG to rs2246809; C, CT to rs2617170; G, CG to rs2617171; and G, CG to rs1983526. Linkage disequilibrium analysis revealed that rs1049174, rs2617160, rs2617170, and rs2617171 constituted the haplotype block-1 variant (hb-1v) (r² ≥ 0.89). Two predominant haplotypes of hb-1v were identified based on the allele content and included CTCG and GATC. This study is the first to evaluate the allelic and genotype frequency distribution of rs1049174, rs2255336, rs2617160, rs2246809, rs2617170, rs2617171, and rs1983526 in the population of Mexico City.     

Association of single nucleotide polymorphisms in interleukin 12 (IL-12A and -B) with asthma in a Chinese population

Increasing evidence has indicated that genetic variants may contribute to immune dysregulation and susceptibility to noninfectious inflammatory diseases. Cytokines, including interleukin 12 (IL-12), play a key role in the regulation of the immune system. The aim of this study was to investigate whether single nucleotide polymorphisms (SNP) in IL-12A and IL-12B were associated with asthma in a Chinese population. Genotype characteristics were determined in 197 asthma patients and 369 controls by the polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing assay. The genotype and allele frequencies of IL-12A rs568408 demonstrated significant differences between cases and controls (p < 0.001). The AC genotype of rs3212227 was associated with a significantly decreased risk of asthma compared with the AA genotype (p = 0.036). The subjects carrying combined genotypes (rs568408 AG and rs3212227 AC/CC) at both loci had a 2.05-fold increased asthma risk compared with those carrying all other genotypes (p = 0.001). In contrast, individuals carrying combined genotypes of rs568408 GG and rs3212227 AC/CC were associated with a significantly decreased risk of asthma compared with those carrying the combined genotypes of rs568408GG and rs3212227AA (p = 0.009). No significant difference was reported for rs2243115 between cases and controls. These results suggest that the SNPs in IL-12A rs568404 and IL-12B rs3212227 may individually and jointly contribute to the risk of asthma in a Chinese population.     

Common variation in genes related to immune response and risk of childhood leukemia

An abnormal immune response to common infection(s) may be a plausible etiological mechanism in childhood leukemia. We investigated whether 931 tagging single nucleotide polymorphisms (SNPs) selected in gene regions related to immune response are associated with childhood leukemia susceptibility in a hospital-based case-control study (63 cases and 148 controls) conducted among Korean children. The AT or TT genotype of rs7939734 in Fas-associated protein with death domain (FADD) was associated with increased risk of childhood leukemia compared with the AA genotype (odds ratio [OR] = 2.26, 95% confidence interval [95% CI] = 1.20-4.25, p(trend) = 0.0007, min p = 0.002, false discovery rate [FDR] p = 0.17). The CG or GG genotype of rs2301696 in TRPM5 was associated with decreased risk of childhood leukemia compared with the CC genotype (OR = 0.30, 95% CI = 0.14-0.63, p(trend) = 0.002, min p = 0.004, FDR p = 0.17). Our findings suggest that genetic polymorphisms in immune response genes might play a role in childhood leukemia development with limited biologic evidence.