Association of solute-linked carrier family 26 member A3 gene polymorphisms with ulcerative colitis among Chinese patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of single nucleotide polymorphisms (SNPs) and haplotypes of solute-linked carrier family 26 member A3 (SLC26A3) gene with ulcerative colitis (UC) among Chinese patients.</p><p><b>METHODS</b>For 416 UC patients and 584 controls, 5 SNPs of the SLC26A3 gene (rs17154444, rs7810937, rs7785539, rs2108225 and rs6951457) were determined with a SNaPshot method. Linkage disequilibrium (LD) and haplotype were analyzed for all subjects.</p><p><b>RESULTS</b>The G allele and AG+GG genotype of rs2108225 were more prevalent in UC patients compared with the controls (65.14% vs. 58.65%, P=0.030; 87.02% vs. 81.85%, P=0.012, respectively). The C allele and TC+CC genotype of rs17154444 were more prevalent in patients with severe UC than in other patients (14.00% vs. 6.01%, P<0.01; 28.00% vs. 11.48%, all P<0.01). Similar conclusion may also be drawn for C allele and GC+CC genotype of rs7785539 (8.00% vs. 7.38%, P=0.011; 16.00% vs. 13.93%, P=0.017, respectively). The SNPs rs17154444, rs7810937, rs7785539 and rs2108225 were found to be in strong LD. Compared with the controls, the T-A-G-G haplotype was more prevalent in UC patients (62.60% vs. 58.20%, P=0.017), whereas the T-G-G-A haplotype was less common in UC patients (27.40% vs. 31.60%, P=0.041).</p><p><b>CONCLUSION</b>Variations of the SLC26A3 rs2108225 may enhance the risk of UC. The rs17154444 and rs7785539 polymorphisms of the SLC26A3 gene are correlated with the severity of UC. The T-A-G-G haplotype formed by rs17154444, rs781093, rs7785539 and rs2108225 of the SLC26A3 gene may increase the risk for UC, whereas the T-G-G-A haplotype may decrease this risk.</p>

Analysis of single nucleotide polymorphisms and haplotypes of FCGR2A gene among patients with ulcerative colitis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of several single nucleotide polymorphisms and haplotypes of the FCGR2A gene with ulcerative colitis (UC) among Chinese patients.</p><p><b>METHODS</b>For 198 UC patients and 356 healthy controls, the alleles and genotypes of the FCGR2A gene (rs1801274, rs10800309 and rs6696854) were detected with a multiplex SNaPshot technique. All subjects were also subjected to linkage disequilibrium and haplotype analyses.</p><p><b>RESULTS</b>The mutant homozygote (CC) of the FCGR2A gene rs1801274 polymorphism was less frequent among UC patients compared with the controls (5.56% vs. 11.80%, P=0.017, OR=0.440, 95%CI: 0.221-0.875). However, the allelic and genotypic distributions of other two SNPs did not differ significantly between the two groups (all P>0.05). Furthermore, no association of the three SNPs (rs1801274, rs10800309 and rs6696854) of the FCGR2A gene with the severity and location of the UC was found (all P>0.05). The three SNPs were shown to be in a strong linkage [rs1801274-rs10800309 (D'=0.863, r=0.634); rs1801274-rs6696854 (D'=0.753, r=0.546); rs10800309-rs6696854(D'=0.990, r=0.802)]. Moreover, the frequency of T-A-T haplotype was higher among the UC patients compared with the controls (67.40% vs. 60.93%, P=0.032, OR=1.326, 95%CI: 1.024-1.717).</p><p><b>CONCLUSION</b>Our findings suggested that the mutant homozygote (CC) of the FCGR2A gene (rs1801274) may have a protective role among Chinese patients with UC. Moreover, the T-A-T haplotype formed by rs1801274, rs10800309 and rs6696854 may confer a higher risk for UC.</p>

Association of inflammatory bowel disease with the polymorphisms and haplotypes of fucosyltransferase 3 gene / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of inflammatory bowel disease with polymorphisms and haplotypes of Fucosyltransferase 3 (FUT3) gene.</p><p><b>METHODS</b>A total of 389 patients with ulcerative colitis (UC), 274 patients with Crohn's disease (CD), and 492 controls were collected. Three single nucleotide polymorphisms (SNPs) of the FUT3 gene (rs28362459, rs3745635 and rs3894326) were determined by direct sequencing. Linkage disequilibrium and haplotype analysis were performed using a Haploview 4.2 software.</p><p><b>RESULTS</b>Compared with the controls, the allele and genotype distributions of FUT3 gene did not significantly differ between the UC and CD groups (all P>0.05). By stratified analysis, the mutant allele (A) and genotype (GA+AA) of the FUT3 gene (rs3745635) were significantly increased in the UC group with distal colitis compared with the controls (P<0.01, P<0.05, respectively). The mutant allele (G) and genotype (TG+GG) of the FUT3 gene (rs28362459) as well as the mutant allele (A) of FUT3(rs3745635) were significantly increased in patients with ileocolonic CD and ileal CD as compared with the controls (P<0.05, P<0.01, P<0.05, respectively). The frequency of mutant allele (G) of FUT3(rs28362459) was higher in stricturing CD patients than in the controls (P<0.05). In addition, the three polymorphic loci of FUT3 gene were shown in complete linkage disequilibrium [rs3894326/rs3745635 (D'=1.0, r2=0.017), rs3894326/rs28362459 (D'=0.937, r2=0.311), rs3745635/rs28362459 (D'=0.944, r2=0.448)]. However, the frequency of each haplotype was not significantly different between the UC and CD groups compared with the controls (all P>0.05).</p><p><b>CONCLUSION</b>FUT3 (rs3745635) mutation may increase the risk of distal colitis. FUT3 (rs28362459 and rs3745635) mutations may engender the increased risk of ileocolonic and ileal CD. Moreover, FUT3 (rs28362459) polymorphism may influence the incidence of stricturing CD.</p>

Effect of heat shock protein 27 on the cardiac dysfunction induced by endotoxemia / 中华急诊医学杂志

Objective To study the effects of heat shock proetin 27(Hsp27)on the cardiac dysfunction induced by endotoxemia.Method All experiments were performed in the geriatric lab of the First Affiliated Hospital Of Nanjing Medical University,and in the Animal Model Center of Nanjing University.The genotyping of the transgenic mice with cardiac-specific overexpression of Hsp27(Hsp27 Tg)was assayed by PCR and the expression of Hsp27 was determined by western blot.Hsp27 Tg and its wild type littermates(WT)were intraperitoneally injected with LPS(10 mg/kg),and 24 hours later,cardiac function was measured by echocardiography(n=6/group).The accumulated mice mortality was recorded within 70 hous after intraperitoneal injection of LPS(20mg/kg)(n=37/WT,n=27/Hsp27Tg).The NF-kB activity for cardiac-tissue samples was analyzed by electrophoretic mobility shift assay(ENSA)and for cell culture samples by dual-reporter gene assay(n=4/group).The comparison of multiple groups was performed by one-way analysis of variance(ANOVA),and comparison of two groups was performed by Scheffe-test.Survival curves were analyzed by the log-rank test.P＜0.05 wns considered to be significant.Results The high expression of Hsp27 exhibited in myocardium of Hsp27 Tg,whereas not in myocardium of WT.LPS significantly reduced the cardiac function both in Hsp27 Tg and WT.However,compaled with LPS-treated WT,cardiac function was more significantly improved as evidenced by the increases of EF by 27.33%and FS by 37.09%(P＜0.01 or P＜0.05).Seventy hours after LPS injection,the mortality was 11.11% in Hsp27 Tg and 37.84% in WT.Compared with WT,the survival rate of Hsp27 Tg significantly increased(P＜0.05).The NF-kB activation was significantly inhibited by Hsp27(P＜0.01 or P＜0.05).Conclusions The high cardiac-specific expression of Hsp27 significantly inhibits cardiac dysfunction induced by endotoxemia,and at the same time improve the survival rate.The mechanism may be connected with Hsp27 downregulating NF-kB-activation induced by LPS.

Relationship between the susceptibility to sporadic colorectal adenocarcinoma and the genetic polymorphisms of glutathione S-Transferase M1,T1 in Chinese Hans / 肿瘤研究与临床

Objective To investigate the relationship between the genetic polymorphisms of glutathione S-Transferase M1,T1 and the susceptibility to sporadic colorectal adenocarcinoma(SCRAC) and smoking and alcohol consumption in Chinese Hans.Methods Multiplex polymerase chain reaction (M-PCR) was used in the study of genetic polymorphisms of GSTM 1,T1 gene.Logistic analysis was performed to elucidate the roles of GSTM1,GST1,smoking and alcohol.Results The null GSTM1,T1 genotypes could increase the susceptibility to SCRAC(OR=1.711,95% CI:1.043～2.805;OR=1.734,95% CI:1.057～2.843),but smoking and alcohol consumption made no significant effect on SCRAC(OR=0.584,95% CI:0.356～0.958;OR=0.378.95% CI:0.217～0.657).Further stratification of the SCRAC patients by chnical features showed that there were no relationship between the GST M1,T1 genotype and the age of the SCRAC patients.But the frequency of null GSTM1 genotype was significantly associated with distal colon adenocarcinoma (P=0.021),colorectal adenocarcinoma of Dukes C classification (P=0.003) and poor difierentiation (P=0.020),respectively.The frequency of null GSTF1 genotype was only higher in colorectal adenocarcinoma of Dukes C classification(P=0.041).No relationship was found between the location,the degree of differentiation and the frequency of null GSTF1 genotype(P＞0.05).Furthermore,the frequencies of homozygous deletion in GSTM1,T1 genes were found to be significantly increased in SCRAC patients than those in healthy controls(38.9%VS25.7%.P=0.023).Conclusion The GST genotype is strongly correlated with SCRAC incidence in Chinese Hans.The null GSTM1,T1 genotypes can enhance the genetic susceptibility to SCRAC.while smoking and alcohol consumption have no significant effect on the susceptibility to SCRAC.