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>

The analysis of genetic polymorphisms and haplotype of the Trail gene in the patients with ulcerative colitis / 中华消化杂志

Objective To explore the association between genetic polymorphisms and haplotypes of tumor necrosis factor-related apoptosis inducing ligand (Trail) and ulcerative colitis (UC).Methods A total of 331 patients with UC and 832 age and sex-matched healthy controls were collected.After Trail gene was amplified by PCR,the genetic polymorphisms of three single nucleotides (G1525A/G1588A/C1595T) in 3' non coding regions of Trail gene were examined by direct sequencing.The relation between Trail haplotype and UC was analyzed.Results Compared with control group,the frequencies of variant allele A and genotype GA+ AA in Trail G1525A were significantly lower in UC group (both P＜0.01).The frequencies of variant allele A and T in Trail G1588A and C1595T were also significantly lower in UC group than that of control group,and the difference was statistically significant (both P ＜ 0.01 ).In mild and moderate UC patients,the frequencies of variant allele T and CT+TT in Trail C1595T were 49.15％ and 64.51％,in severe UC patients were 72.37％ and 84.21％,and the differences were significant between the two groups (OR=2.710 and 2.935,95％CI:1.598～4.596 and 1.188～7.249,all P ＜0.05).In severe UC patients,the frequency of variant allele A in Trail G1525A was 48.69％,which was higher than that of mild and moderate patients (35.16％,OR=1.750,95％CI:1.082～2.830,P=0.021).In UC group,the frequency of AAT haplotype was significantly lower than that of controls (43.09％ vs 58.41％,P＜0.01).The frequency of GAT haplotype was significantly higher in UC group (10.15％vs 0.18％,95％ CI:0.005 ～ 0.051,P＜ 0.01).Conclusion The genetic polymorphisms and haplotypes of Trail (G1525A/G1588A/C1595T) gene may be closely correlated with the susceptibility to UC.

The expressions of cathepsin D,H and L in hepatocellular carcinoma / 中华消化杂志

Objective To determine the expression of cathepsin D (CD), cathepsin H (CH) and cathepsin L (CL) in human primary hepatocellular carcinoma (HCC), and to investigate their mechanisms. Methods The protein expression of CD, CH and CL in hepatic specimens consisted of control (n = 17), HCC (n = 37) and paracancerous (n = 28) tissues were detected by immunohistochemistry. The relative values of CD, CH and CL protein expression were examined with absorbent density analysis. Data were analyzed using SPSS11. 5 software. The univariate analysis was used to compare the difference among groups. Results The mean absorbance of CD, CH and CL proteins in HCC tissues (1.21± 0.33, 0. 89 ± 0.22 and 1.16± 0. 25, respectively) were significantly higher in comparison with those in control tissues (0. 19 ± 0. 07, 0. 24 ± 0. 12 and 0. 28 ± 0. 14,respectively) and in paracancerous tissues (0.27±0.13,0. 31± 0.14 and 0. 36±0.15)(all P values =0.0001). Whereas there was no difference between control and paracancerous tissues with respect to CD, CH and CL proteins (P ＞0. 05). Three proteins immunohistochemically appeared as a lot of diffused spots and stripes staining in cytoplasma of HCC tissues,but only a few scatted spots staining was found in control and paracancerous tissues. Conclusion The high expression of CD, CH and CL protein in primary HCC may be important markers for carcinogenesis and malignant progress.

The associations of methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms and ulcerative colitis / 中华内科杂志

Objective To investigate the association between the genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and ulcerative colitis (UC) of Han ethnic population in Zhejiang, China. Methods Two hundred and seventy-four consecutive patients with UC and 726 healthy controls (HC) were studied. The genetic polymorphisms of MTHFR (C677T and A1298C) were genotyped using PCR-RELP methods. Results The frequencies of variant allele and genotype in MTHFR A1298Cgene were higher in UC patients than in the HC (35.77% vs 29. 96%, P =0. 013; 52. 19% vs 44. 90%,P=0.039; respectively). However, there were no significant discrepancies of the allele and genotype frequencies in the MTHFR C677T gene between the UC patients and the HC (P ＞ 0. 05 ). In addition, the MTHFR 677Tr homozygote, T allele and 677CT/1298AC compound genotype were more prevalent in patients with extensive colitis than in those with distal colitis (37. 66% vs 14. 72% ,P = 0. 0002; 49. 35% vs 32.99% ,P =0. 0004; 29. 87% vs 15.23% ,P =0. 006; respectively). Furthermore,the variant allele in the MTHFR A1298C gene (C) in severe UC patients was significantly lower than in mild and moderate UC patients (18.97% vs 33. 88% ,P =0. 022). Conclusion The genetic polymorphisms of MTHFR C677T and A1298C are obviously associated with Han ethnic population with UC in Zhejiang province.