摘要:目的:研究高血壓病患者過氧化物酶體增殖物激活受體(PPAR)γ2基因Pro12Ala多態性與血糖水平之間的關系。方法:納入177名原發性高血壓患者,其中空腹血糖(FBG)lt;5.6 mmol/L組65例, FBG≥5.6 mmol/L組112例,收集一般資料;分別測定空腹及餐后2小時血糖、胰島素;對PPARγ2 基因Pro12Ala多態性與各臨床變量的關系進行研究。結果:FBGlt;5.6 mmol/L組和FBG≥5.6 mmol/L組Pro和Ala等位基因頻率分別為0.333,0.034及0.602,0.031;PP和PA基因型頻率分別為0.299,0.068及0.571,0.062;無AA型純合子。以體重指數(BMI)分層后,BMIlt;25組內,FBG與PPARγ2基因型相關（P=0.029)。以基因型分組比較,PA組空腹血糖水平和胰島素抵抗指數都低于PP組(Plt;0.05)。結論:成都地區高血壓患者PPARγ2基因Pro12Ala多態性與空腹血糖水平相關,且攜帶Ala基因者空腹血糖水平較低,胰島素抵抗較輕,推測該突變可能有減輕高血壓病患者胰島素抵抗,改善糖代謝異常的作用。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 reveal the association between the single nucleotide polymorphism (SNP) of v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) gene rs17820943 locus and non-syndromic cleft l ip with or without cleft palate (NSCL/P) in the southern Chinese Han population. Methods Genotyping of MAFB gene rs17820943 polymorphism was carried out in 300 patients with NSCL/P, 354 normal controls, and an additional 168 case-parent trios with matrix-assisted laser desorption/ionisation time-of-fl ight (MALDI-TOF) mass spectrometry. Then based on the genotypingresults, both a case-control association study and a case-parent trio association study were performed. Results Significant differences were found in the allele and genotype frequencies of rs17820943 locus between case and control groups (Pallele=0.001 and Pgenotype=0.002, respectively). To be specific, the odds radio (OR) values and 95% confidence interval (95%CI) of allele T (frequencies of cases ∶ controls = 0.358 ∶ 0.448) and genotype TT (frequencies of cases ∶ controls = 0.110 ∶ 0.195) were ORT = 0.69 (95%CI: 0.55-0.86) and ORTT = 0.43 (95%CI: 0.26-0.70), respectively. Subsequent case-parent trio analysis also indicated an association between MAFB rs17820943 variant and the risk of NSCL/P (ORT vs. C = 0.55, 95%CI: 0.41-0.75, P value of transmission disequilibrium test was 0.000). Conclusion Polymorphism of MAFB gene rs17820943 locus is associated with NSCL/P in the southern Chinese Han population; MAFB rs17820943 variant may be a susceptible gene of NSCL/P.
Objective To systematically evaluate anti-platelet effect of clopidogrel influenced by CYP2C192,3 polymorphism in patients with cardiovascular diseases, in order to provide references for its safe medication. Methods Literature was retrieved in electronic databases covering EMbase, PubMed, The Cochrane Library, CBM and CNKI from establishment dates to November, 2011. Observational studies and clinical trials were included, cross-checked, assessed and pooled for meta-analysis. meta-analysis was performed using the software RevMan 5.1. Results A total of 13 articles including 14 trials (n=36 855) were included. The results of meta-analysis showed that: a) there was no significant difference in the incidences of cardiovascular events between CYP2C192,3 carriers and CYP2C191 carriers; b) the risk of stent thrombosis in CYP2C192,3 carriers was significantly higher than that in CYP2C191 carriers (Plt;0.000 1), and the relative risk of CYP2C192,3 carriers increased 92% within one month (Plt;0.000 1); c) as for bleeding events, there were no significant differences between CYP2C192,3 carriers and CYP2C191 carriers. Conclusion Compared with CYP2C191 carriers, CYP2C192,3 carriers have a higher risk of stent thrombosis in clopidogrel-treated patients, but there are few differences in cardiovascular and bleeding events between the two carriers. Therefore, CYP2C192,3 carriers with cardiovascular diseases and ready to receive PCT are suggested to pay more attention to stent thrombosis when using clopidogrel. We propose that patients with cardiovascular diseases and ready to receive PCT should have CYP2C19 tests to determine the use of antiplatelet drug (clopidogrel) to avoid thrombus.
ObjectiveTo investigate the association between polymorphism of V4,F+1 in ADAM33 (adisintegrin and metalloproteinase 33) gene and COPD in a northwestern Uighur population. MethodsA total of 100 Uighur COPD patients and 140 healthy volunteers were recruited in the study. Genotypes were determined by restriction fragment lengthpolymorphism(PCR-RFLP). All subjects had a epidemiological investigation including modified british medical research council(mMRC),COPD assessment test(CAT),and pulmonary function test. The 100 Uighur COPD patients were assessed by revised GOLD2011. ResultsAssessed by revised GOLD2011,the patients of A,B and C grade accounted for 22%,35% and 30%,respectively. There was no statistical significance in the distributions of the V4,F+1 alleles between the patients and the controls(P>0.05). There was no statistical significance between SNPs in ADAM33(V4 and F+1) with the decreased lung function and the grade of COPD(P>0.05). ConclusionThere was no association between polymorphism of V4,F+1 in ADAM33 gene and COPD in a northwestern Uighur population.
Objective To evaluate the relationship between angiotension-converting enzyme (ACE) gene polymorphism and susceptibility to cerebral hemorrhage among the Han Chinese population. Methods We electronically searched CNKI, CBM, VIP, and Wanfang technological periodical full-text databases from January, 1998 to January, 2009. We identified case-control studies of ACE gene polymorphism and cerebral hemorrhage among the Han Chinese population, and assessed the quality of included studies. The data were quantitatively analyzed by RevMan 4.3 software. Results Meta-analysis results showed that the pooled OR value of cerebral hemorrhage subjects among the Han Chinese population with at least one D allele was 1.42 (95%CI1.13 to1.78). The pooled OR values of cerebral hemorrhage with DD and II genotype were 1.9 (95%CI1.32 to 2.74) and 0.80 (95%CI0.63 to 1.01) respectively. Conclusion ACE gene polymorphism is significantly associated with susceptibility to cerebral hemorrhage in the Han Chinese `population.
ObjectiveTo analyze the causal relationship between SARS-CoV-2 infection and retinal vascular obstruction by mendelian randomization (MR). MethodsA two-sample MR analysis utilizing summary statistics from genome-wide association studies (GWAS) in European populations was conducted. The GWAS data for SARS-CoV-2 infection comprised cases of common infection (2 597 856), hospitalized infection (2 095 324), and severe infection (1 086 211). Data on retinal vascular obstruction were obtained from the FinnGen database, which included 203 269 cases of retinal artery obstruction and 182 945 cases of retinal vein obstruction (RVO). Inverse variance weighting (IVW), random effects models, weighted median (WM), MR-Egger regression, simple models, and weighted models were used to analyze the bidirectional causal relationship between different SARS-CoV-2 infection phenotypes and retinal obstruction. The Q statistic was used to assess heterogeneity among single nucleotide polymorphisms (SNP), while MR-Presso was utilized to detect SNP outliers, and MR-Egger intercept tests were performed to evaluate horizontal pleiotropy. ResultsThe MR analysis, using IVW, random effects models, MR-Egger, WM, and weighted models, indicated no significant association between common SARS-CoV-2 infection, hospitalized infection, severe infection, and retinal vascular obstruction (P＞0.05). Additionally, retinal vascular obstruction did not show a significant association with the various SARS-CoV-2 infection phenotypes (P＞0.05). In the simple model, a significant association was found between severe SARS-CoV-2 infection and RVO (P＜0.05), as well as between RVO and common SARS-CoV-2 infection (P＜0.05). No heterogeneity was observed in the IVW and MR-Egger analyses (P＞0.05). The MR-Egger test provided no evidence of horizontal pleiotropy (P＞0.05), and MR-Presso detected no outlier SNP. ConclusionThe findings of this study do not support a causal relationship between SARS-CoV-2 infection and the occurrence of retinal vascular obstruction.
Objective To explore the correlation between the single nucleotide polymorphism (SNP) in the promotor of hepatic l ipase (HL) gene and untraumatic avascular necrosis of the femoral head (ANFH). Methods Between January 2007 and June 2009, 243 patients with ANFH were treated (case group), including 143 cases of steroid-induced, 79 cases of alchol-induced, and 21 cases of idiopathic. There were 156 males and 87 females with an age ranged from 16 to 64 years. Atotal of 96 normal individuals (matched for age, sex, and nation) served as control group. The blood sample of all subjects were collected to extract DNA. The promotor of HL was sequenced to find the SNP. A statistic on the frequencies of the genotype and the allele of the SNP was made. The frequencies of the genotype and the allele were analyzed with χ2 test according to case-control principle. Results The rs59644784 and rs1800588 were found in the sequenced region. It was accorded with Hardy-Weinbery genetic equil ibrium law in rs59644784 and rs1800588 of the control group and case group. There was no significant difference in the allele and genotype of rs59644784 and rs1800588 between the control group and case group (P gt; 0.05). The two SNPs existed complete l inkage disequil ibrium according to the l inkage disequil ibrium analysis. Conclusion The heterozygosity of the SNP is not consistency, and heterozygosity may be associated with the diversity of the race. ANFH is not associated with rs59644784 and rs1800588 SNPs.
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 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.
Objective To investigate the relationship between cyclooxygenase-2 (COX-2) gene polymorphism and genetic susceptibility to esophageal cancer. Methods The PubMed and EMbase databases were searched from the date of their establishment to January 1st, 2011 to collect the case-control studies on COX-2 polymorphism and susceptibility to esophageal cancer. For the population genotype distributions of both esophagus cancer group and control group, their odds ratios (ORs) and 95% confidence intervals (CIs) were taken as the effect indexes, either the fixed or random effect model was applied to conducted Meta-analysis in homozygote comparison, dominant and recessive genetic models, and the publication bias was assessed then. All statistical analyses were conducted with Stata11.0 software. Results A total of five case-control studies were included. The results of meta-analyses showed for the COX-2-765Ggt;C polymorphism, the CC+GC genotype was associated with the risk of esophageal cancer in a dominant genetic model (CC+GC vs. GG: OR=1.806, 95% CI 1.050 to 3.106); for the COX-2-1195Ggt;A polymorphism, the AA genotype was associated with the risk of esophageal cancer in homozygote comparison and recessive genetic models, the AA+GA genotype was associated with the risk of esophageal cancer in a dominant genetic model. Conclusion It is suggested that COX-2 polymorphism may be associated with genetic susceptibility to esophageal cancer.