Von Hippel-Lindau gene single nucleotide polymorphism (rs1642742) may be related to the occurrence and metastasis of HBV-related hepatocellular carcinoma

It is well-known that microRNAs are able to regulate the expression of target mRNAs through complementary base-pairing to their 3′-untranslated regions (3′UTR) sequences. This study aimed to investigate whether single nucleotide polymorphisms resided in the 3′UTR sequences in patients with chronic hepatitis B viruses (HBV) infection are associated with the development and metastasis of hepatocellular carcinoma (HCC). Seventeen single nucleotide polymorphisms in the 3′UTR sequence of 10 genes regulated or affected by hepatitis B virus X protein were found by bioinformatics methods. Two hundred fifteen patients with HBV-related HCC and 216 patients with chronic HBV infection were recruited. Through case-control study, only found that the von Hippel-Lindau gene rs1642742 (G>A) may be associated with the occurrence and metastasis of HCC. The ORs of the frequencies of rs1642742 A allele versus G allele were 1.424 (P = .038, 95% confidence interval [CI] = 1.019–1.989) between HBV-related HCC and chronic HBV infection group and were 2.004 (P = .037, 95%CI = 1.031–3.895) between tumor metastasis and non-metastasis group, respectively. Through multivariate regression analysis, we also found that rs1642742 AA genotype was an independent risk factor for tumor metastasis (odds ratio = 2.227, 95% CI = 1.043–4.752, P = .038) in HBV-related HCC group. Our study suggested that Von Hippel-Lindau rs1642742 contributed to susceptibility to developing HCC and correlated with tumor metastasis.     

Association of a single nucleotide polymorphism in the constitutive androstane receptor gene with bone mineral density

Background:   Nuclear receptors play an important role in bone metabolism. In bone cells, the vitamin D receptor (VDR) and the steroid and xenobiotic receptor (SXR) are activated by vitamin D and vitamin K2, respectively. VDR and SXR are the NR1I subfamily members of nuclear receptors. We speculated that the constitutive androstane receptor ( CAR ), the third member of the NR1I subfamily, also could be implicated in the regulation of bone metabolism. Therefore, we analyzed expression of CAR mRNA in osteoblasts and then examined association of a single nucleotide polymorphism (SNP) in the human CAR gene at intron 2 (IVS2–99C>T, rs2502815) with bone mineral density (BMD).
Methods:   Expression levels of CAR mRNA were analyzed during the culture course of rat primary osteoblasts. Association of an SNP in the CAR gene with BMD was examined in 548 healthy Japanese postmenopausal women.
Results:   CAR mRNA increased at day 16 and then increased during culture of rat primary osteoblasts. The increase of CAR mRNA was parallel with the increase of alkaline phosphatase expression, a differentiation marker of osteoblasts. As a result of association study of an SNP in the CAR gene at intron 2, subjects with the CC genotype ( n  = 208) had significantly higher BMD than subjects with the TT or CT genotype ( n  = 340) (lumbar spine BMD, P  = 0.0185; total body BMD, P  = 0.0416).
Conclusion:   CAR mRNA was expressed and regulated in primary osteoblasts. A genetic variation at the CAR gene locus is associated with BMD, suggesting an involvement of the CAR gene in bone metabolism.     

Vascular endothelial growth factor (VEGF) gene (VEGFA) polymorphism can predict the prognosis in acute myeloid leukaemia patients

Increased angiogenesis, mediated by vascular endothelial growth factor (VEGF), was associated with poor prognosis in acute myeloid leukaemia (AML) patients. The current study investigated the impact of VEGF gene ( VEGFA ) single nucleotide polymorphisms (SNPs) on treatment outcomes for AML. Four VEGFA SNPs were analysed for −2578C>A (rs699947), −460T>C (rs833061), +405G>C (rs2010963) and +936 C>T (rs3025039) loci in 138 AML patients. The +936 CC/CT genotype showed strong correlation with favourable leukaemia-free survival (LFS) at 2 years (51·3%) versus with +936 CC genotype (33·6%, P  =   0·03). Strong linkage disequilibrium was noted among loci −2578, −460 and +405, but not with +936. Accordingly, four haplotypes were generated based on the genotypes of −2578, −460 and +405 as follows: CTC (40·2%), CTG (35·0%), ACG (22·0%) and ATC (1·2%). The LFS and event-free survival (EFS) inversely correlated with CTG haplotype ( P  =   0·03 for LFS; P  =   0·05 for EFS). We scored the VEGFA polymorphism marker based on +936 C>T genotype and CTG haplotype for −2578, −460 and +405, which demonstrated a good correlation with the treatment outcomes: LFS ( P  =   0·01), EFS ( P  =   0·03) and overall survival ( P  =   0·01). The VEGFA +936 C>T genotype and CTG haplotype seemed to have an additive effect to predict the prognosis in AML patients.     

NKX3.1基因rs1512268单核苷酸多态性与前列腺癌风险关系的初步研究

目的 探讨NKX3.1基因的常见变异rs1512268单核苷酸多态性与中国人前列腺癌发生的关系及相关危险因素的相互作用. 方法 选取122例前列腺癌患者和年龄匹配的105例男性(前列腺癌特异抗原＜4μg/L,且无前列腺癌家族史者)作为对照,采用聚合酶链反应-高分辨熔解曲线(PCR-HRM)技术结合测序验证法检测NKX3.1基因rs1512268单核苷酸多态性的分布. 结果 前列腺癌组中GG、AG和AA基因型分布分别为42例(33.4％)、66例(54.1％)和14例(11.5％);正常对照组中三种基因型分布分别为45例(42.9％)、51例(48.6％)和9例(8.6％);两组间基因型频率(x2=1.70,0.69,0.52)和等位基因频率(x2=1.575)的分布差异无统计学意义(P＞0.05).NKX3.1基因rs1512268单核苷酸多态性的不同基因型与前列腺癌患者的年龄、Gleason评分和PSA浓度以及临床分期等指标间均无相关性(P＞0.05). 结论 NKX3.1基因rs1512268单核苷酸多态性与中国人前列腺癌的发生无明显相关性,可能不是中国人前列腺癌发病的遗传危险因素.     

三基因单核苷酸多态性与汉族人群2型糖尿病的相关性研究

目的：研究rs3923113-GRB14,rs1802295-VPS26A,rs7178572-HMG20A三基因单核苷酸多态性（SNPs）与2型糖尿病（T2DM）及相关代谢指标的相关性。方法：用高分辨率溶解曲线（HRM）小片段基因分型方法检测300例T2DM者及300例健康体检者3SNP位点基因型及等位基因频率分布。结果：各SNP基因型分布符合遗传平衡定律。rs231362（KCNQl）的风险基因C患病风险是T等位基因的1．058倍（P=0．012,OR=1．058,95％CI：1．012-1．106）。rs231362（KCNQl）的3种基因型（TT、CT、CC）在T2DM组与对照组中的分布频率分别为0．7％、19．9％、75．6Voo和2．7％、25．6％、71．7％,2组基因型分布差异有统计学意义（P=0．031）。该位点在其隐性模型中（CCVSCT＋TT）,2组差异有统计学意义（P=0．028,OR=1．11,95％CI：1．01～1．22）。rs3923113-GRBl4、rs7178572-HMG20A基因型分布在病例组与对照组中未见显著性差异。我们分析了对照组血糖血脂与各SNP位点基因型之间的关系,rs3923113在显性模型[（TT＋GT）／GG]下TT＋GT组总胆固醇（Tc）值低于GG组;TT＋GT组高密度脂蛋白（HDL-C）1．07（0．90-1．19）mmol／L低于GG组1．21（1.02-1．41）mmol／L,P值分别为0．017与0．036。结论：rs231362-KCNQl可能与中国人群T2DM发病有关。rs3923113-GRBl4与TC及HDL-C升高有关。     

TCF7L2基因单核苷酸多态性与妊娠期糖尿病的相关性研究

目的 探讨转录因子7类似物2(TCF7L2)基因rs290487、rs11196205、rs11196218位点单核苷酸多态性(SNP)与妊娠期糖尿病(GDM)的关系.方法 采用病例对照研究方法,选取中国北方地区无血缘关系的糖耐量受损(IGT)孕妇158例、GDM孕妇335例作为病例组,正常妊娠妇女647例作为对照组.提取所有受试者基因组DNA,用连接酶检测反应(LDR)分析TCF7L2基因rs290487、rs11196205、rs11196218位点基因型,并进行相关分析.结果 在rs290487位点,C等位基因频率在病例组为41.6%,明显高于对照组的36.3%(P=0.012).病例组中CC基因型频率为18.7%,明显高于对照组的14.0%(P=0.033).CC基因型GDM发病风险与CT+TT基因型相比,比数比(OR)为1.418(95%CI 1.028～1.955),经logistic回归校正混杂因素后,OR值为1.518(95%CI 1.064～2.166).结论 TCF7L2基因rs290487位点SNP可能在GDM遗传易感性中起重要作用,CC基因型可能是其发生的危险因素.

Abstract：

Objective To investigate the relationship between gene polymorphism of transcripion factor 7-like 2 (TCF7L2) at positions rs290487, rs11196205, rs11196218 and gestational diabetes mellitus (GDM) in Chinese women.Methods In 1140 unrelated pregnant Northern Chinese women (335 women with GDM, 158 gestational cases with impaired glucose tolerance and 647 pregnant non-diabetic controls) ,three single nucleotide polymorphisms (rs290487, rs11196205, and rs11196218) in the TCF7L2 gene were genotyped using ligase detection reaction (LDR).In the present study, cases with GDM and impaired glucose tolerance (IGT) were indistinguishable clinically and biochemically, and were combined into case group.Results The frequency of C allele of rs290487 was 41.6% in case group, being significantly higher than that in control group (36.3%, P=0.012).There was significant difference in the frequency of CC genotype between case group and control group (18.7% vs 14.0%, P=0.033).Compared with T allele carriers, CC genotype carriers had a 1.418-fold increased risk of GDM (95% CI 1.028-1.955).After adjusting for age, body mass index, family history of diabetes,systolic blood pressure,and diastolic blood pressure, pregnant women with CC genotype carriers of rs290487 were more prone to hyperglycemia compared with the T allele carriers (OR 1.518, 95% CI 1.064-2.166).Conclusions The TCF7L2 rs290487 variant may contribute to the genetic predisposition to GDM.CC genotype is likely to be associated with an increased risk of GDM in the pregnant Chinese women.     

EGFR基因单核苷酸多态性与胃癌的相关性

目的探讨表皮生长因子受体（EGFR）rs 28384375C／T单核苷酸多态性在胃癌发生、发展中的作用。方法采用PCR．限制性片断长度多态性（PCR-RFLP）法对61例胃癌患者（胃癌组）和20例健康查体正常者（对照组）的EGFR基因单核苷酸多态性进行检测,并分析其与幽门螺杆菌（HP）感染的相关性。结果①EGFR位点：胃癌组EGFR基因型频率分别为C／T26．22％、T／T73．78％;对照组分别为C／T5．00％、T／T95．00％,两组均未发现C／C基因型;P=0．0316;②C、T等位基因频率：胃癌组分别为13．11％、86．89％,对照组分别为2．50％、97．50％,P=0．0443;③胃癌组两种基因型者HP感染检出率无统计学意义;④EGFRC／T多态性与胃癌淋巴结转移、远处转移、TNM分期和组织分化程度相关（P〈0．05）;与患者性别、年龄、胃癌发生部位、浸润深度、原发肿瘤侵犯范围和组织类型无相关性。结论EGFR单核苷酸多态性可促进胃癌的发生发展;与HP感染无明显相关性。     

Association between APE1 rs1760944 and rs1130409 polymorphism with prostate cancer risk: A systematic review and meta-analysis

Background:Recently, some studies have suggested that the association of apurinic/apyrimidinic endonuclease 1 (APE1) gene polymorphism with prostate cancer (PCa) risk, but there are still some controversies. Hence, we elaborated the relationship between APE1 rs1760944 and rs1130409 gene and PCa risk through systematic literature review and meta-analysis.Methods:As of March 2020, EMBASE, PubMed, the Cochrane Library, Science Direct/Elsevier, MEDLINE and CNKI were used for systematic literature retrieval to investigate the correlation between APE1 rs1760944 and rs1130409 gene polymorphism with PCa risk. Meta-analysis was performed using Review Manager and Stata software.Results:Seven studies were distinguished, consists of 1769 cases of PCa patients and 2237 normal controls. Our results illustrated that there are significant correlation between the APE1 rs1760944 gene polymorphism and PCa in all genetic models (P < .05). The combined odds ratios and 95% confidence intervals were as follows: Additive model (ORs 0.62, 95%, CI [0.39, 0.97]); Codominant model (ORs 0.74, 95% CI [0.58, 0.95]); Dominant model (ORs 0.75, 95%, CI [0.59, 0.95]); Recessive model (ORs 0.63, 95% CI [0.41, 0.96]); Allele model (ORs 0.78, 95% CI [0.65, 0.94]). There also have significant associations between APE1 rs1130409 polymorphisms and PCa in all genetic models (P < .05). The combined odds ratios and 95% confidence intervals were as follows: Additive model (ORs 1.37, 95%, CI [1.01, 1.85]); Codominant model (ORs 1.21, 95% CI [1.01, 1.44]); Dominant model (ORs 1.33, 95%, CI [1.02, 1.73]); Recessive model (ORs 1.74, 95% CI [1.06, 2.85]); Allele model (ORs 1.14, 95% CI [1.00, 1.29]).Conclusion:This study suggests that APE1 rs1760944 polymorphisms might be a protective factor of PCa, and APE1 rs1130409 is suggested to be a risk factor of PCa. APE1 rs1760944 and rs1130409 polymorphisms may be used in the risk assessment of PCa.     

EphA2, vascular endothelial growth factor,and vascular endothelial growth factor correlate with adverse outcomes and poor survival in patients with glioma

Purpose:To assess expression levels of Ephrin type-A receptor 2 (EphA2), vascular endothelial growth factor (VEGF), and von Willebrand factor (vWF), and assess their potentials as prognostic biomarkers to predict the risk of poor survival in patients with primary lower grade glioma.Method:The study included75 patients with histopathologically confirmed primary glioma (World Health Organization Grade IV). All patients underwent combined surgery and postoperative radiotherapy for the management of primary glioma. Immuno-histochemical analysis was performed to evaluate expression levels ofEphA2 and VEGF. Evaluation of tumor microvessel density was also performed at angiogenesis hot spots due to tumor growth. Main outcomes of the study were the prognostic efficiencies of EphA2, VEGF, and vWF in primary low-grade glioma, as well as whether their expression levels were associated with cancer progression.Results:Of the patients with glioma, 67% had very strong expression of EphA2. Overall survival was inversely correlated with the expression of EphA2. Regarding VEGF expression, 38 patients (51%) had strong expression, 29 patients (39%) had weak expression, and 8 patients (11%) had no expression. Strong VEGF expression was associated with poor prognosis and poor survival.Conclusion:EphA2, VEGF, and vWF could be considered prognostic markers for assessment of primary glioma.     

上海地区胰升糖素样肽1受体基因多态性与2型糖尿病相关

目的研究胰升糖素样肽1受体(GLP1R)基因的单核苷酸多态性(SNP)与上海地区汉族人群2型糖尿病的相关性。方法选取上海地区无亲缘关系的2型糖尿病患者360例及正常对照313名,其中糖尿病患者分为肥胖组192例(BMI>28kg/m2,且仅用口服降糖药治疗)及非肥胖组168例(BMI<25kg/m2,且用胰岛素治疗),采用等位基因特异的实时PCR,对GLP1R基因位点rs2268657进行基因分型,并通过相关分析,研究该位点与2型糖尿病的相关性。结果GLP1R基因rs2268657位点AA、AG、GG基因型频率在对照人群中分别为0.086,0.447,0.446;在非肥胖糖尿病组中分别为0.155,0.375,0.470,在肥胖糖尿病组中分别为0.109,0.500,0.391。在正常人基因型AA频率与非肥胖糖尿病组相比差异有统计学意义(OR=1.939,P<0.05),而与肥胖糖尿病组相比差异无统计学意义。结论GLP1R基因多态性位点rs2268657可能与胰岛素分泌不足为主的2型糖尿病有关。     

胰岛素受体底物-2基因多态性与2型糖尿病的相关性研究

目的 研究北京地区汉族人群中胰岛素受体底物-2（IRS-2）基因密码子1057g/a多态性与2型糖尿病及其中间表型的相关性。方法 选取北京地区的中国汉族患者110例，对照组80例。用聚合酶链反应-限制性内切酶片段长度多态性（PCR-RFLP）的方法检测IRS-2基因密码了1057g/a多态性。结果 （1）IRS-2基因密码子1057g/a多态性的a等位基因频率在糖尿病组和对照组中分别为26.4%和36.3%。（2）糖尿病组aa基因型频率明显低于对照组，分别为5.5%和18.7%(P=0.016),Logistic相关分析表明：aa基因型为2型糖尿病的保护性因素，OR值为0.28(95%CI=0.09-0.91,P=0.03)。（3）不同基因型组间血压、血脂，胰岛素抵抗指数及胰岛β细胞功能指数等均差异无显著性。结论 中国北方地区汉族人群中IRS-2基因密码子1057g/a多态性的aa基因型在2型糖尿病中明显减少。但2型糖尿病各种中间表型自欺欺人持征在不同基因型间均无明显差异。上述结果有待于进一步扩大样本量来加以确认。     

miRNA-146a rs2910164位点的单核苷酸多态性与原发性肝癌术后复发的相关性

目的探讨miRNA-146a rs2910164位点的单核苷酸多态性与肝癌术后复发的相关性。方法选取于东风医疗集团茅箭医院行肝癌根治性切除术的89例原发性肝癌患者,按照术后是否复发分为复发组和非复发组。应用Taq Man探针法对miRNA-146a rs2910164 G/C位点的基因分型,比较两组各基因型的频率及miRNA-146a的单核苷酸多态性与肝癌术后复发风险的关系。计量资料组间比较采用成组t检验,计数资料采用χ2检验,并采用多因素Logistic回归分析可能影响肝癌复发的因素。结果非复发组miRNA-146a G/C三种基因型符合Hardy-Weinberg平衡定律(P0.05)。肝癌术后复发组和非复发组miRNA-146a G/C基因型频率差异有统计学意义(χ2=9.115,P=0.010),其中复发组miRNA146a(rs2910164)CG基因型频率明显高于非复发组(χ2=4.013,P=0.039),GG基因型频率明显低于非复发组(χ2=9.046,P=0.003)。多因素Logistic分析显示肿瘤直径、miRNA146a(rs2910164)CG基因型是肝癌术后复发的危险因素(OR=1.075,P=0.003 9;OR=6.215,P=0.001 4),miRNA146a(rs2910164)GG基因型是肝癌术后复发的保护因素(OR=0.382,P=0.002 5)。结论 miRNA-146a rs2910164 C/G位点的多态性与肝癌根治术后复发相关,rs2910164位点的CG基因型可能是引起肝癌患者术后复发的危险因素。     

白细胞介素-18基因单核苷酸多态性及其血清含量与溃疡性结肠炎的相关性

目的 探讨白细胞介素(IL)-18基因单核苷酸多态性(SNP)及其血清含量与溃疡性结肠炎(UC)的相关性.方法 采用PCR扩增和直接测序法检测50例UC患者及128名健康对照者的IL-18基因5'端4个SNP位点(rs187238 G/C、rs5744228 G/A、rs360718 A/C、rs360717 G/A),同时检测受试者血清IL-18含量.结果 UC组血清IL-18含量明显高于对照组,两组间差异有统计学意义(3029.9±111.7)pg/ml比(133.2±39.4)pg/ml,(P<0.01).rs187238 C、rs360718 C、rs360717 A位点与UC显著相关(X~2=9.26,P<0.01),该3个位点的单倍体型频率在UC组和对照组间差异亦有统计学意义(X~2=7.04,P<0.01).与对照组相比,UC组含等位基因型C者的血清IL-18含量明显升高(P<0.05).结论 IL-18基因的SNP与其血清含量存在相关性,提示其基因位点多态性及血清含量可能与UC易感性相关.     

Association of single nucleotide polymorphism rs2076185 in chromosome 6P24.1 with premature coronary artery diseases in Chinese Han population

Objectives To study the association of single nucleotide polymorphism (SNP) rs2076185 in chromosome 6p24.1 with the premature coronary artery diseases (PCAD) in Chinese Han population. Methods A total of 1382 patients were divided into the PCAD group and the control group based on their coronary arteriography (CAG) results. Their SNP rs2076185 were analyzed by the mass-spectrometry. Their allele and genotype frequency in Hardy-Weinberg equilibrium were calculated for assessment. Logistic regression was employed to remove confounding factors and correlate SNP rs2076185 with PCAD. Results The allele and genotype frequencies of the control group were in Hardy-Weinberg equilibrium (P > 0.05). The frequencies of allele G of rs2076185 were 54.2% in the PCAD group and 49.5% in the control group. The difference was significant (P = 0.042). The genotype distribution of rs2076185 of the two groups was also significantly different. The univariate analysis showed that the rs2076185 polymorphisms were associated with the PCAD only in the additive model (OR: 0.828, 95% CI: 0.711?0.964, P = 0.014), and in the dominant model (OR: 0.753, 95% CI: 0.591?0.958, P = 0.021). After removing the confounding variables, the rs2076185 polymorphisms was associated with PCAD in the additive model (OR: 0.775, 95% CI: 0.648?0.928, P = 0.005), in the dominant model (OR: 0.698, 95% CI: 0.527?0.925, P = 0.012), and in the recessive model (OR: 0.804, 95% CI: 0.538?0.983, P = 0.038). Conclusion Allele G of rs2076185 reduces the PCAD risks in Chinese Han population, therefore it could be a coronary artery diseases protective factor in Chinese Han population.     

Association of the insulin-like growth factor binding protein 3 (IGFBP-3) polymorphism with longevity in Chinese nonagenarians and centenarians

Human lifespan is determined greatly by genetic factors and some investigations have identified putative genes implicated in human longevity. Although some genetic loci have been associated with longevity, most of them are difficult to replicate due to ethnic differences. In this study, we analyzed the association of 18 reported gene single nucleotide polymorphisms (SNPs) with longevity in 1075 samples consisting of 567 nonagenarians/centenarians and 508 younger controls using the GenomeLab SNPstream Genotyping System. Our results confirm the association of the forkhead box O3 (FOXO3) variant (rs13217795) and the ATM serine/threonine kinase (ATM) variant (rs189037) genotypes with longevity (p=0.0075 and p=0.026, using the codominant model and recessive model, respectively). Of note is that we first revealed the association of insulin-like growth factor binding protein 3 (IGFBP-3) gene polymorphism rs11977526 with longevity in Chinese nonagenarians/centenarians (p=0.033 using the dominant model and p=0.035 using the overdominant model). The FOXO3 and IGFBP-3 form important parts of the insulin/insulin-like growth factor-1 signaling pathway (IGF-1) implicated in human longevity, and the ATM gene is involved in sensing DNA damage and reducing oxidative stress, therefore our results highlight the important roles of insulin pathway and oxidative stress in the longevity in the Chinese population.     

Association of XPG rs2094258 polymorphism with gastric cancer prognosis

BACKGROUND The xeroderma pigmentosum group G(XPG)gene at chromosome 13q33 consists of 15 exons,which may be related to the occurrence and development of gastric cancer(GC).AIM To examine the association of several common single nucleotide polymorphisms(SNPs)of the XPG gene with GC risk and survival.METHODS Five SNPs of XPG(rs2094258,rs751402,rs873601,rs2296147,and rs1047768)were genotyped by PCR restriction fragment length polymorphism in 956 histologically confirmed GC cases and 1012 controls in North China.GC patients were followed for survival status and,if deceased,cause of death.Logistic regression and Cox regression were used for analysing associations of XPG SNPs with risk of GC and prognosis,respectively.For rs2094258,heterozygous model(CT vs CC),homozygous model(TT vs CC),recessive model(TT vs CT+CC),and dominant model(TT+CT vs CC)were analyzed.RESULTS None of the examined loci were statistically associated with GC risk,although rs2296147 was marginally associated with GC risk(P=0.050).GC patients with the rs2094258 CT+CC genotype showed worse survival than those with the TT genotype(log-rank test,P=0.028),and patients with the CC genotype had a tendency of unfavourable prognosis compared with those with the TT+CT genotype(log-rank test,P=0.039).The increase in C alleles of rs2094258[hazard ratio(HR)=1.19,95%confidence interval(CI):1.02-1.45,P=0.037]were associated with the long-term survival of GC cases.Other risk factors for survival included tumor differentiation(HR=4.51,95%CI:1.99-8.23,P<0.001),lymphovascular invasion(HR=1.97,95%CI:1.44-3.01,P<0.001),and use of chemotherapy(HR=0.81,95%CI:0.63-0.98,P=0.041).CONCLUSION The XPG rs2094258 polymorphism may be associated with overall survival in GC patients.     

Association study of single nucleotide polymorphism in tryptophan hydroxylase 1 gene with adolescent idiopathic scoliosis: A meta-analysis

Background:Adolescent idiopathic scoliosis is a common spinal deformity among children and adolescents worldwide with its etiology uncertain. Over a decade, a single nucleotide polymorphism rs10488682 in tryptophan hydroxylase 1 (TPH1) gene has been investigated in several association studies. We perform this study to summarize the current evidence of TPH1 rs10488682 polymorphisms and adolescent idiopathic scoliosis (AIS).Methods:Six databases were systematically searched: PubMed, Embase, Cochrane Library, Web of Science, Chinese Biomedical Literature, and Wanfang database. Eligible case–control studies related to TPH1 and AIS were selected. Reference lists of them were reviewed for more available studies. Two authors independently screened and evaluated the literature and extracted data. The odds ratios and 95% confidence intervals were derived in association tests. Subgroup analysis was conducted by ethnicity. Sensitivity analysis was performed to examine the stability of the overall results.Results:A total of 1006 cases and 1557 controls in 3 independent studies were included for meta-analysis. Statistical significance was discovered in heterozygote model (AT vs AA: OR = 1.741, 95%Cl = 1.100–2.753, P = .018 < .05, I² = 0%), recessive model (AA vs AT + TT: OR = 0.640, 95%Cl = 0.414–0.990, P = .045 < .05, I² = 0%) and over-dominant model (AT vs AA + TT: OR = 1.366, 95%Cl = 1.115–1.673, P = .003 < .05, I² = 84.7%) in overall populations. Similar associations were also found in the Caucasian population. No significant associations were found in other genotypic comparisons and allelic comparisons.Conclusions:Statistically significant correlations were discovered between the TPH1 rs10488682 polymorphisms and AIS. Heterozygous AT genotype seems to be risky with an over-dominant effect. Ethnicity appears to modify the disease association.Registration:Not applicable.     

The APLNR gene polymorphism rs7119375 is associated with an increased risk of development of essential hypertension in the Chinese population: A meta-analysis

Hypertension (HT) has recently been defined as a systolic blood pressure (BP) of ≥130 mm Hg and/or a diastolic BP of ≥80 mm Hg. It is important to further understand the pathophysiology of essential HT as its proportion is larger among most of the diagnosed HT cases. The apelin and apelin receptor (APLNR) are known to play roles in regulating BP, but the putative associations of single nucleotide polymorphisms in the APLNR gene with the risk of development of essential HT have not yet been fully investigated. Herein, we conducted a meta-analysis to investigate the relationship between single nucleotide polymorphisms in the APLNR gene and the risk of essential HT.We conducted a search in the PubMed and Web of Science databases for eligible studies. The pooled odds ratios (ORs) with their 95% confidence intervals (CI) were calculated using random-effects models when heterogeneity was expected across the studies. Otherwise, fixed-effect models were used.Regarding the SNP rs7119375, 5 studies were analyzed, which included a total of 3567 essential HT patients and 3256 healthy controls. Four of the 5 studies were from China and 1 was from Mexico. The meta-analysis showed the existence of a significant association between the AA genotype of rs7119375 and the risk of developing essential HT in the Chinese population, as determined using additive and recessive models (OR, 2.11; 95% CI, 1.12–3.96; I² = 86% for AA vs GG. OR, 1.53; 95% CI, 1.21–1.94; I² = 28% for AA vs AG. OR, 1.88; 95% CI, 1.13–3.12; I² = 79% for AA vs AG + GG).Our study showed, for the first time, the existence of an association between rs7119375 and the risk of development of essential HT in the Chinese population, although the sample size was small and there was considerable population heterogeneity. The apelin/APLNR system could be a novel therapeutic target for the treatment of essential HT, and more studies are warranted to further investigate the association.