Glutathione-S-Transferase Polymorphisms (GSTM1, GSTT1 and GSTP1) and Acute Leukemia Risk in Asians: a Meta-analysis

The association between glutathione-S-transferase polymorphisms (GSTM1, GSTT1 and GSTP1) and riskof acute leukemia in Asians remains controversial. This study was therefore designed to evaluate the preciseassociation in 23 studies identified by a search of PubMed and several other databases, up to December 2013.Using random or fixed effects models odds ratios (ORs) with corresponding 95% confidence intervals (CIs) werecalculated. Heterogeneity across studies was assessed, and funnel plots were constructed to test for publicationbias. The meta-analysis showed positive associations between GST polymorphisms (GSTM1 and GSTT1 butnot GSTP1) and acute leukemia risk [(OR=1.47, 95% CI 1.18-1.83); (OR=1.32, 95% CI 1.07-1.62); (OR=1.01,95% CI 0.84-1.23), respectively] and heterogeneity between the studies. The results suggested that the GSTM1null genotype and GSTT1null genotype, but not the GSTP1 polymorphism, might be a potential risk factors foracute leukemia. Further well-designed studies are needed to confirm our findings.     

Interleukin-12 p40 gene (IL12B) polymorphisms and the risk of cervical caner in Korean women

Objective

The aim of this study was to investigate whether IL12B polymorphisms might be associated with increased risk and invasiveness of cervical cancer in Korean women.

Study design

Peripheral blood samples from patients with invasive cervical cancer (n = 154) and non-cancer controls (n = 191) were used to detect three biallelic IL12B polymorphisms at IVS2 −912, IVS4 +314, 3′UTR +1188 sites by performing SNaPshot assay. Allelic frequencies, genotype distributions, and haplotype patterns in the case group were compared with those in the control group. The relationships between these polymorphisms and cancer invasiveness were also evaluated by collating the clinicopathologic parameters including FIGO stage, lymph node status, histologic type, and parametrial invasion. The used analytic methods are chi-square test and logistic regression analysis.

Results

Allelic frequencies of cases (G, 0.853; A, 0.147) were not significantly different from controls (G, 0.796; A, 0.204) in IVS2 −912G/A SNP (P = 0.054). GG genotype of IVS2 −912G/A SNP showed increased risk for cervical cancer compared with AA genotype (P = 0.040). The IVS2 −912G:IVS4 + 314A haplotype, IVS2 −912G:IVS4 +314A:3′UTR +1188A haplotype, and IVS2 −912G:IVS4 +314A:3′UTR +1188C haplotype were also significantly associated with increased risk for cervical cancer. A subgroup analysis of the clinicopathologic parameters in cancer group also showed that there is no significant association between IL12B polymorphisms and cervical cancer invasiveness.

Conclusions

This study suggests that IVS2 −912GG genotype and IVS2 −912G:IVS4 +314A haplotype of IL12B gene are associated with increased risk for cervical cancer in Korean women.     

钙蛋白酶10基因多态性与多囊卵巢综合征患者糖耐量及脂代谢异常的相关性

目的 探讨钙蛋白酶10(CAPN-10)基因56位点单核苷酸多态性(SNP-56)与多囊卵巢综合征(PCOS)患者糖耐量及脂代谢异常的相关性.方法 选取山东地区PCOS患者334例(PCOS组),健康妇女304例(对照组),采用熔解温度不同的基因分型法检测CAPN-10基因SNP-56,并采用免疫化学发光法测定泌乳素、卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇、睾酮水平.PCOS组同时测定血糖、血脂、血清胰岛素水平.结果 (1)基因型及等位基因频率分布两组比较,差异均无统计学意义(P＞0.05).(2)在PCOS组,口服葡萄糖耐量试验(OGTF)180 min血糖水平AA基因型者为(5.7±2.2)mmol/L,GA基因型者为(4.9±1.2)mmol/L,GG基因型者为(4.9±1.4)mmol/L,分别比较,差异均有统计学意义(P均＜0.01);总胆固醇(TC)水平AA基因型者为(4.9±1.0)mmol/L,GA基因型者为(4.5±0.9)mmol/L,两者比较,差异也有统计学意义(P＜0.05).(3)在PCOS组,有糖尿病家族史者共44例,AA基因型频率为22.7%(10/44),GA+GG基因型频率为77.3%(34/44),GG基因型频率为34.1%(15/44);无糖尿病家族史者共290例,AA基因型频率为11.0%(32/290),GA+GG基因型频率为89.0%(258/290),GG基因型频率为47.2%(137/290),有无糖尿病家族史者AA与GA+GG基因型频率比较及AA与GG基因型频率比较,差异均有统计学意义(x2=4.751,x2=5.697;P均＜0.05).在PCOS组,有肿瘤家族史者共21例,AA基因型频率为33.3%(7/21),GA+GG基因型频率为66.7%(14/21),GG基因型频率为19.0%(4/21);无肿瘤家族史者共313例,AA基因型频率为11.2%(35/313),GA+GG基因型频率为88.8%(278/313),GG基因型频率为47.3%(148/313).结论 (1)CAPN-10基因SNP-56与PCOS的遗传易感性无明显相关性,但与PCOS患者糖、脂代谢异常有明显相关性.(2)CAPN-10基因SNP-56与PCOS患者糖尿病家族史及肿瘤家族史相关,应重视对高危PCOS个体的随访.     

细胞周期调控基因p21和p27单核苷酸多态性与卵巢上皮性癌的关系

目的 探讨细胞周期调控基因p21和p27的单核苷酸多态性(SNP)与卵巢上皮性癌(卵巢癌)发病风险的关系.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测234例卵巢癌患者(卵巢癌组)和284例健康妇女(对照组)p21基因C/T和p27基因V/G SNP位点基因型和等位基因的频率分布.结果 (1)对照组妇女p21基因的C/C、C/T和T/T基因型频率分别为34.2%、49.6%和16.2%,C和T等位基因频率分别为59.0%和41.0%;卵巢癌组患者3种基因型频率分别为28.2%、53.0%和18.8%,C和T等位基因频率分别为54.7%和45.3%.两组基因型频率和等位基因频率分别比较,差异均无统计学意义(P＞0.05).3种基因型频率在4种病理类型的卵巢癌中的分布有明显差异(P=0.02),C/C基因型降低子宫内膜样癌的发病风险(OR为0.56,95%CI为0.32～0.98).(2)对照组妇女p27基因V/V、V/G和G/G基因型频率分别为88.4%、10.9%租0.7%,V和G等位基因频率分别为93.8%和6.2%;卵巢癌组患者的基因型频率分别为93.6%、5.1%和1.3%,V和G等位基因频率分别为96.2%和3.8%.两组基因型频率分布比较,差异有统计学意义(P=0.04),等位基因频率分布比较,差异则无统计学意义(P=0.09).与V/G和G/G基因型比较,V/V基因型增加卵巢癌的发病风险(OR为1.92,95%CI为1.02～3.63).结论 p21基因C/T多态性的C/C基因型可能降低子宫内膜样癌的发病风险,p27基因的V/V基因型可能是卵巢癌发病的潜在危险因素.     

Impact of polymorphism in <Emphasis Type="Italic">IL-1RA</Emphasis> gene on the risk of cervical cancer

Introduction Cervical cancer, the second most common malignancy in women worldwide, is almost invariably associated with infection by human papillomavirus (HPV). However, although many women are infected with high-risk types of HPV, only a subset of infected women will ever develop cervical cancer. Therefore, host genetic factor may play a role in cervical carcinogenesis. Several studies suggested that immunological components play a key role in the development of cervical cancer. Polymorphism in the IL-1RA gene was associated with various malignant diseases. Data are lacking for cervical cancer. Materials and methods In a case−control study we analyzed the polymorphism of IL-1RA in 150 women with cervical cancer and 209 healthy controls. Genomic DNA fragments were amplified by PCR. Results There was a strong significantly protective association between heterozygous AB genotype and HPV 18 (OR = 0.11, 95% CI = 0.04–0.30, p = 0.0000000). Similarly this result was demonstrated, in combined AB + BB genotypes of IL-1RA with HPV 18 (OR = 0.12, 95% CI = 0.05–0.30, p = 0.0000000) and HPV type 16 + 18 (OR = 0.18,95% CI = 0.08–0.38, p = 0.000005). We found high protective significant association between heterozygous genotype AB with adenocarcinoma (OR = 0.19, 95% CI = 0.09–0.40, p = 0.0000002) as well. Conclusion These findings therefore suggest that the IL1-RA polymorphism is associated with cervical cancer.     

Impact of methylenetetrahydrofolate reductase (<Emphasis Type="Italic">MTHFR</Emphasis>) codon (677) and methionine synthase (<Emphasis Type="Italic">MS</Emphasis>) codon (2756) on risk of cervical carcinogenesis in North Indian population

Cervical cancer continues to be the most common cause of death among women in developing countries. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are critical enzymes of folate metabolic pathways. In this work, we have conducted a case–control study to assess the role of these two polymorphisms in cervical cancer development. We obtained blood samples from 200 women with cervical cancer and from equal matched controls and analysed using PCR-RFLP method. We found that the methylenetetrahydrofolate reductase variant CT and CT + TT genotypes decreased cervix cancer risk, statistically significant (OR:0.30, 95% CI: 0.18–0.51, P < 0.001 for CT and OR:0.29, 95% CI: 0.18–0.49, P = 0.0000006 for CT + TT). Similarly in those patients who used oral contraceptive with variant CT genotype, there was statistically highly significant reduced risk of cervix cancer (OR:0.25, 95% CI: –0.12–0.49, P < 0.001) of methylenetetrahydrofolate reductase gene. For the methionine synthase, 2756 variant AG and AG + GG genotypes were similarly associated with highly significant reduced risk of cervix cancer (OR: 0.13, 95% CI: 0.07–0.26, P < 0.001 for AG, and OR: 0.15, 95% CI: 0.08–0.27, P < 0.001 for AG + GG) genotypes. In conclusion, our study suggested that methylenetetrahydrofolate reductase and methionine synthase polymorphisms might have protective effect on the risk of cervical cancer in the North Indian women.     

Genetic polymorphisms in vasoactive genes and preeclampsia: a meta-analysis

There are controversies in reports on the association of polymorphisms in endothelial nitric oxide synthase, angiotensinogen, angiotensin receptor type 1 and angiotensin-converting enzyme genes with an increased risk of developing preeclampsia. We performed a systematic search of published case-control studies through the PubMed database up to January 2006, and report the results of a meta-analysis of polymorphisms investigated in more than five studies: Glu298Asp in eNOS gene (9 analyses involving 1055 patients and 1788 controls), Met235Thr in AGT gene (13 analyses involving 1128 patients and 2278 controls), and intron 16 insertion-deletion polymorphism in ACE gene (10 analyses involving 1121 patients and 1361 controls). Statistically significant associations with preeclampsia were identified for the Met235Thr/AGT polymorphism: OR 1.65 (95% CI 1.19, 2.29) if the polymorphism is considered under the dominant genetic model, and OR 1.54 (95% CI 1.12, 2.11) under the recessive model. For insertion-deletion/ACE polymorphism, statistical significance was demonstrated when the polymorphism was considered under the recessive model: OR 1.51 (95% CI 1.17, 1.94). No single polymorphism was identified as having a major effect.     

急性心肌梗死患者白细胞介素-6血清水平及其基因多态性研究

目的探讨急性心肌梗死(AMI)患者白细胞介素-6(IL-6)血清水平和IL-6基因-572C/G多态性在中国汉族人群中的分布频率及其与AMI易感性的关系。方法对145例AMI患者和170名健康对照人群进行IL-6血清水平和基因-572C/G多态性检测,IL-6血清水平采用ELISA法测定,基因型检测应用PCR/RFLP方法。结果AMI患者血清IL-6水平显著高于对照组[(25.36±19.91)pg/ml比(4.59±2.69)pg/ml,P<0.01]。AMI组CC、CG、GG三种基因型频率为52.41%、41.38%、6.21%;对照组为64.12%、34.70%、1.18%。两组间基因型、等位基因频率比较有显著性差异,前者CG GG基因型频率与G等位基因频率均显著高于后者(P均<0.05)。CG GG基因型人群患AMI的风险是CC基因型人群的1.62倍(95%CI:1.03~2.55,P<0.05)。不同基因型人群间血清IL-6水平无差异。结论AMI患者血清IL-6水平高,-572CG GG基因型频率高,IL-6基因-572G等位基因可能是中国汉族人群AMI发生的易感基因之一。     

湖南地区人群HLA单倍型的多态性研究

目的 了解湖南地区人群HLA单倍型的多态性。方法 采用PCR-SSP法对3664名湖南籍健康人群进行HLA-A、B、DR位点的低分辨基因分型,计算HLA-AB、HLA-BDR、HLA—ABDR单倍型的连锁不平衡参数及频率,并与其他人群进行比较。结果 共检出350种HLA-AB单倍型、408种HLA—BDR单倍型、1935种HLA-ABDR单倍型。检出具备强连锁的HLA-AB单倍型36种、HLA-BDR单倍型48种,其中,频率较高的单倍型为A2-B46、A11-B60、A24-B60、B46-DR9、B60-DR15、B60-DR4、A2-B46-DR9、A33-B58-DR3、A11-B75-DR12。结论 湖南地区人群的HLA单倍型分布特点与我国南方人接近。但有其自身特征,A2-B＊8102、A24-B46-DR9、A11-B51-DR9可能为湖南人群特有的单倍型。     

ABCA1基因R219K多态性与广西汉族心血管疾病的关系

目的:探讨ATP结合盒转运子A1(ATP-Binding Cassette Transporter 1,ABCA1)基因R219K多态性与广西汉族心血管疾病的关系。方法:采用PCR-RFLP技术,对无血缘关系的心血管疾病人群113例和非心血管疾病人群61例的ABCA1基因R219K位点G→A(Arg219Lys)进行检测,分析其基因多态性。结果:在心血管疾病组中,除HDL比非心血管疾病组低外,其余血脂指标均高,其中TC、LDL与ApoB在两组间的差异有统计学意义(P<0.05)。广西汉族心血管疾病人群的RK型频率最高,RR型次之,KK型频率最低;心血管疾病组的KK基因型频率(0.129)低于非心血管疾病组(0.148),但差异无统计学意义(P>0.05)。RR、RK和KK三种基因型的血脂水平差异没有统计学意义(P>0.05),女性心血管疾病人群KK型的HDL比RR型的高(P>0.05),而KK型的TG和VLDL比RR型低(P<0.05)。结论:ABCA1基因R219K变异对心血管疾病可能具有保护作用,但具体保护机制及ABCA1基因R219K在心血管疾病人群中基因型分布频率也有待于更大样本的观察和进一步深入研究。