摘要:目的:研究高血压病患者过氧化物酶体增殖物激活受体(PPAR)γ2基因Pro12Ala多态性与血糖水平之间的关系。方法:纳入177名原发性高血压患者,其中空腹血糖(FBG)lt;5.6 mmol/L组65例, FBG≥5.6 mmol/L组112例,收集一般资料;分别测定空腹及餐后2小时血糖、胰岛素;对PPARγ2 基因Pro12Ala多态性与各临床变量的关系进行研究。结果:FBGlt;5.6 mmol/L组和FBG≥5.6 mmol/L组Pro和Ala等位基因频率分别为0.333,0.034及0.602,0.031;PP和PA基因型频率分别为0.299,0.068及0.571,0.062;无AA型纯合子。以体重指数(BMI)分层后,BMIlt;25组内,FBG与PPARγ2基因型相关（P=0.029)。以基因型分组比较,PA组空腹血糖水平和胰岛素抵抗指数都低于PP组(Plt;0.05)。结论:成都地区高血压患者PPARγ2基因Pro12Ala多态性与空腹血糖水平相关,且携带Ala基因者空腹血糖水平较低,胰岛素抵抗较轻,推测该突变可能有减轻高血压病患者胰岛素抵抗,改善糖代谢异常的作用。Abstract: Objective:To study the association between the Pro12Ala polymorphism in peroxisome proliferatorsactivated receptorγ2 ( PPARγ2 ) gene and blood glucose levels in patients with primary hypertension. Methods：The Pro12Ala polymorphism in PPARγ2 was determined by polymerase chain reactionrestriction fragment length polymorphism (PCRRELP) in 177 subjects with primary hypertension of the Han people in Chengdu of China, including 65 subjects with fasting blood glucose (FBG)lt;5.6 mmol/L and 112 subjects with FBG≥5.6 mmol/L; the clinical characteristics including height, weight, OGTT(0h and 2h) of the subjects were detected and the realationship between the Pro12Ala polymorphism and the clinical characteristics were analysed. Results: The allele frequencies in the group with FBGlt;5.6 mmol/L and FBG≥5.6 mmol/L were 0.333, 0.602 for Pro and 0.034, 0.031 for Ala. The genotype frequencies were 0.299, 0.571 for PP and 0.068, 0.062 for PA, and there was no AA. In the group with BMIlt;25, the Pro12Ala polymorphism was associated with FBG （P=0.029). the Ala allele had a negative relationship to the FPG and insulin resistance index (IRI) (Plt;0.05).Conclusion: The data showed that the Pro12Ala polymorphism was associated with FBG., and The allele Ala probably had benefits to glycometabolic disturbance in patients with primary hypertension by declining insulin resistance.
Objective To systematically review the correlation between polymorphism of DNA methyltransferase 1(DNMT1) rs16999593 and the susceptibility of breast cancer. Methods Databases such as PubMed, EMbase, Web of Science, Chinese Biomedical Literature Database, CNKI, WanFang, and VIP database were searched from inception to Mar. 2017 to collect case-control studies on the correlation between DNMT1 rs16999593 C/T polymorphism and the susceptibility of breast cancer. Two reviewers independently identified the literatures according to inclusion and exclusion criterias, extracted data, and assessed the quality of the included studies. The meta-analysis was performed by using RevMan 5.3 software. Results A total of 5 studies involving 1 741 cases and 1 917 control subjects were included. The results of meta-analysis showed that, dominate model ［TT+TC vs. CC: OR=0.63, 95% CI was (0.30, 1.30), P=0.21］, homozygous model ［TT vs. CC: OR=1.01, 95% CI was (0.70, 1.47), P=0.95］, heterozygous model ［TC vs. CC: OR=0.44, 95% CI was (0.18, 1.04), P=0.06］, and additive model ［T vs. C: OR=1.29, 95% CI was (0.90, 1.86), P=0.16］ were not significantly related to breast cancer, but recessive gene model was related to breast cancer ［TT vs. TC+CC: OR=1.74, 95% CI was (1.01, 3.00), P=0.04］. Conclusion The current studies showed that, DNMT1 rs16999593 TT genotype decreases the susceptibility of breast cancer.
The association between single nucleotide polymorphism and disease is a typical representation of genetic association studies. Compared with the traditional dichotomous data, single nucleotide polymorphism data has its own characteristics, and 5 genetic models are commonly performed in meta-analysis. In this paper, we show how to use the " meta” package in R software to conduct meta-analysis of single nucleotide polymorphism research through examples.
Objective To explore the correlation between interleukin-6 (IL-6) 174G/C polymorphism and ischemic stroke risks. Methods Systematic searches of electronic databases as CBM, CNKI, PubMed, MEDLINE and EMbase were performed. Meta-analysis was conducted by using RevMan 5.1.2 and Stata 11.0 software. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Publication bias was tested by funnel plot, Egger’s regression test and Begg’s test. Sensitivity analysis was made by repeating the fixed effects model or random effects model Meta-analysis with each of the studies individually removed. Results A total of 11 publications with 12 studies were identified. The results of meta-analyses showed no significant difference was found in the correlation between IL-6 174G/C polymorphism and ischemic stroke risks (for G/C vs. G/G: OR=0.98, 95%CI 0.78 to 1.24; for C/C vs. G/G: OR=0.75, 95%CI 0.38 to 1.50; for dominant inheritance model: OR=0.93, 95%CI 0.68 to 1.28; for recessive inheritance model: OR=0.80, 95%CI 0.45 to 1.42). In the subgroup analyses on ethnicity, no significant correlation was found. But in the subgroup analyses on source of control population, the hospital-based subgroup showed IL-6 174G/C polymorphism was the protective factor of ischemic stroke (for G/C vs. G/G: OR=0.56, 95%CI 0.40 to 0.79; for C/C vs. G/G: OR=0.17, 95%CI 0.11 to 0.27; for dominant inheritance model: OR=0.40, 95%CI 0.29 to 0.55; for recessive inheritance model: OR=0.24, 95%CI 0.16 to 0.37). Conclusion Meta-analysis bly suggests that the correlation between IL-6 174 G/C polymorphism and ischemic stroke is not significantly different.
Objective To investigate association between –174C/G genetic polymorphism of interleukin-6 (IL-6) and susceptibility to gastric cancer by conducting a meta-analysis. Methods Such databases as PubMed, Embase, The Cochrane Library, Web of Science, CNKI, VIP, and Wanfang Data were searched from inception to January 2017 to collect case-control studies about the correlation between the –174C/G genetic polymorphism of IL-6 and susceptibility to gastric cancer. For the population genotype distributions of both the gastric cancer group and the control group, their odds ratios (OR) and 95% confidence intervals (CI) were taken as the effect indexes were applied to conduct meta-analysis in the homozygote model (CC vs. GG), heterozygote model (GC vs. GG), dominant model (CC+CG vs. GG), recessive model (CG+GG vs. CC), and allelic genetic model (C vs. G). Two reviewers independently screened the literatures, extracted the data, and evaluated the quality of the included studies. The meta-analysis was performed using Stata 12.0 software. Results Thirteen articles were included in the final meta-analysis, covering a total of 2 062 gastric cancer cases and 3 152 controls. The results of meta-analysis showed that there was no correlation between the IL-6 –174C/G genetic polymorphism and the risk of gastric cancer〔CC vs. GG: OR=1.33, 95% CI (0.92, 1.94); GC vs. GG: OR=1.32, 95% CI (0.96, 1.82); CC+CG vs. GG: OR=1.32, 95% CI (0.97, 1.80); CG+GG vs. CC: OR=0.89, 95% CI (0.67, 1.17); C vs. G: OR=1.22, 95% CI (0.98, 1.54)〕. But the results of the subgroup analysis showed there was a significant association between the IL-6 –174 C/G genetic polymorphism and the risk of gastric cancer in Asians〔CC vs. GG: OR=1.80, 95% CI (1.29, 2.50); GC vs. GG: OR=1.51, 95% CI (1.20, 1.90); CC+CG vs. GG: OR=1.60, 95% CI (1.30, 1.96); CG+GG vs. CC: OR=0.60, 95% CI (0.44, 0.83); C vs. G: OR=1.59, 95% CI (1.24, 2.03)〕. However, no association was found in Europeans〔CC vs. GG: OR=1.11, 95% CI (0.90, 1.39); GC vs. GG: OR=1.16, 95% CI (0.98, 1.37); CC+CG vs. GG: OR=1.12, 95% CI (0.96, 1.32); CG+GG vs. CC: OR=1.07, 95% CI (0.88, 1.30); C vs. G: OR=1.04, 95% CI (0.78, 1.41)〕 . Conclusion IL-6 –174C/G genetic polymorphism is associated with susceptibility to gastric cancer in Asians, which is not associated with susceptibility to gastric cancer in Europeans.
ObjectiveTo understand the genetics associations between low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms and susceptibility of osteoporosis in patients with chronic obstructive pulmonary disease (COPD).MethodsThree hundred and seventy-nine patients with acute exacerbation of COPD were divided into groups of non osteoporosis and osteoporosis. Genomic DNA was extracted from all patients. UCSC genome browser and Haploview 4.2 software were used to screen tag single nucleotide polymorphisms (tagSNP) of LRP5 gene. The tagSNP was genotyped by Sequenom MassARRAY SNP detection method. Logistic regression were used to analysis the odds ratio (OR) values and confidence intervals (CI) of each SNP in different genetic models to assess the association between single nucleotide polymorphisms in LRP5 gene and osteoporosis in COPD patients.ResultsEight tagSNPs of LRP5 gene (rs312016 T/C, rs312017 C/T, rs312018 A/G, rs3736228 C/T, rs901823 T/C, rs589963 G/A, rs638051 A/G, rs671494 C/A) were selected for association analysis. Patients of rs901823 carrying C/C genotype had a higher risk of osteoporosis than those carrying T/T and C/T genotypes in COPD patients (in recessive mode, C/C vs. T/T+C/T, OR=9.42, 95%CI=2.01–44.29), P=0.000 431 8).ConclusionsThere is a significant association between rs901823 of LRP5 gene and osteoporosis in patients with COPD. Further studies are needed to discover the mechanism of LRP5 gene polymorphism in the pathogenesis of osteoporosis in COPD patients.
ObjectiveTo understand progress of gene research for chronic venous ulcer (CVU) so as to seek for the best treatment strategy for it.MethodThe literatures about studies on gene polymorphism and variability that leaded to the occurrence and development of CVU in recent years were reviewed and analyzed.ResultsThe CVU was mainly caused by the chronic venous insufficiency (CVI). Many changes in the gene expression had been found in the curable CVU and incurable CVU. The expressions of regulated inflammatory genes, encoding extracellular peptide genes, and encoding different cellular pathways genes in the incurable CVU patients had remarkable differences as compared with the healthy individuals. Although there were more studies on incurable CVU than curable CVU, it was still unable to accurately predict the healing time of CVU. At the same time, genome-wide associations study had not been performed to find single nucleotide polymorphism related to the risk of CVU.ConclusionsAlthough CVU is mainly caused by CVI, not all patients with CVI have ulcer. At present, parts of risk factors of CVU have been known, such as age, iliofemoral vein embolism, deep vein insufficiency, hypertension, obesity, and so on. However, there are fewer studies on heredity, so it is necessary to strengthen its research. Gene expression and gene polymorphism have increasingly become focus of research on causes of chronic inflammation. Genome-wide association study is a gold standard of complex disease genetics, so it is neccessary to further search so as to better understand genetic basis and genetic background of CVU and find the best treatment strategy for improving ulcer healing.
ObjectiveTo understand the genetic polymorphisms of MUC5B and TOLLIP in Chinese patients with idiopathic pulmonary fibrosis (IPF), and to explore whether gene polymorphism variation in Chinese IPF patients can be used as a genetic biomarker for accurate treatment and prognosis judgment.MethodsA total of one hundred and twenty-six patients with IPF were enrolled in this study. The baseline characteristics, total lung capacity (TLC), forced vital capacity (FVC), carbon monoxide diffusion function (DLCO), imaging changes of the patients were followed up. The levels of serum sputum glycosylated antigen-6 (Krebs Von den Lungen-6, KL-6) and B lymphocyte chemotactic factor C-X-C motif chemokine 13 (CXCL13) were detected by chemiluminescent enzyme immunoassay and enzyme-linked immunosorbent assay. The gene MUC5B rs35705950 and TOLLIP rs5743890, rs5743894 single nucleotide polymorphism (SNP) were determined by polymerase chain reaction.ResultsOne hundred and twenty-six patients with IPF were found with AA type by TOLLIP rs5743890 and rs5743894 SNP, accounting for 100.0%; MUC5B rs35705950 SNP was expressed as 116 patients (92.1%) with GG type, and 10 patients (7.9%) with GT type, no TT patients were detected. There was no significant difference in clinical characteristics between the two groups in age and non-smokers (P>0.05). Compared with group G, annual decrease of lung function (FVC, DLCO, and TLC), serum biomarkers (KL-6 and CXCL13), annual increase of reticular and honeycombing lesions, and mortality were significantly lower in group T (P<0.05). The median survival time of IPF patients carrying the MUC5B SNP rs35705950 minor allele (gene phenotype GT) heterozygous was significantly higher than that of homozygous IPF patients with a genetic phenotype of GG.ConclusionsThere are genetic polymorphisms in Chinese patients with IPF. MUC5B rs35705950 and TOLLIP rs5743890, rs5743894 gene subtypes have low mutation rates in the cohort. Compared with homozygous patients of MUC5B SNP rs35705950, heterozygous patients have smaller changes in lung function and radiological image, lower levels of serum KL-6 and CXCL13, and better prognosis.
Objective To systematically evaluate the correlation between endometriosis (EM) in Chinese women and Xba I polymorphism in intron-1 of estrogen receptor α (ER-α) gene. Methods Such databases as PubMed, MEDLINE, The Cochrane Library (Issue 3, 2012), VIP, CBM, WanFang Data and CNKI were searched to collect case-control studies about the correlation between EM and Xba I polymorphism in intron-1 of ER-α gene. The retrieval time was from 1980 to 2012. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data and assessed the quality, and then the meta-analysis was conducted by using RevMan 5.0 and Stata 12.0 software. Results A total of 7 studies involving 676 EM patients and 688 healthy volunteers were included. The results of meta-analyses showed that Chinese women with X/X genotype had similar risk of EM compared to those with x/x genotype (OR=0.95, 95%CI 0.58 to 1.54, P=0.82) or X/x genotype (OR=0.73, 95%CI 0.44 to 1.20, P=0.22). The allele X also showed similar risk of EM compared to the allele x (OR=1.11, 95%CI 0.93 to 1.33, P=0.25). Conclusion At present, it has not yet been found that the incidence of EM in Chinese women is related to the Xba I polymorphism in intron-1 of ER-α gene as well as the allele X. For the quantity and quality limitation of the included studies, this conclusion has to be proved by more studies.
Objective To explore the relationship between alcohol induced osteonecrosis of the femoral head (ONFH) and the single nucleotide polymorphisms (SNP) of methylene tetrahydrofolate reductase (MTHFR) 677 C/T. Methods From July 2005 to May 2008, eighty-nine male patients with alcohol induced ONFH were selected as the patient group, aged from 24 to58 years old (mean 44.3 years old). The time of drinking was about 17 years, 375 mL/day. The imaging evidence showed ONFH with no other history associated to ONFH. Seventy-seven male healthy adults were selected as the control group, aged from 23 to 52 years old (mean 42.7 years old). The time of drinking was about 14 years, 335 mL/day. The imaging evidence showed no ONFH. The 2 mL blood sample was acquired from every subject. DNA was purified from leucocyte at first, then was ampl icated by PCR, the product of PCR was sequenced at last. The SNP of MTHFR 677 C/T was analyzed with SPSS 12.0 software package. Results The TT genotype and T allele frequencies of MTHFR 677 C/T were 27.2% and 52.0% (P gt; 0.05) in the control group, and the distribution of genotype was consistent with Hardy-Weinberg equil ibrium. The genotype frequencies of CC, CT and TT were 23.4% (18 cases), 49.4% (38 cases) and 27.2% (21 cases) in the control group, were 14.6% (13 cases), 36.0% (32 cases) and 49.4% (44 cases) in the patient group; showing statistically significant differences (P lt; 0.05). The allele frequencies of C and T were 48.0% (74) and 52.0% (80) in the control group, and were 32.6% (58) and 67.4% (120) in the patient group; showing statistically significant differences (P lt; 0.05). The frequencies of C, T alleles and TT genotype were higher in the patient group than in the control group, showing statistically significant differences (P lt; 0.05). The odds ratios were 0.523, 1.914 and 2.607, respectively; the 95% confidence interval were 0.335-0.816, 1.226-2.987, 1.359-5.001, respectively. Conclusion The relationship may exist between the SNP of MTHFR 677 C/T and alcohol induced ONFH.