Weibo Liang

The association of interleukin-16 polymorphisms with IL-16 serum levels and risk of colorectal and gastric cancer

Interleukin (IL)-16, a multifunctional cytokine, plays a fundamental role in inflammatory diseases, as well as in the development and progression of tumors. Genetic variation in the DNA sequence of the IL-16 gene may lead to altered cytokine production and/or activity, and this variation may modulate an individuals susceptibility to both colorectal cancer (CRC) and gastric cancer (GC). To test this hypothesis, we investigated the association of IL-16 gene polymorphisms with serum levels of IL-16 and the risk of CRC and GC in a Chinese population. We analyzed single-nucleotide polymorphisms of the IL-16 gene in 596 cancer patients (376 patients with CRC and 220 patients with GC), and also in 480 age- and sex-matched controls using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. Serum IL-16 levels were measured by enzyme-linked immunosorbent assay. The rs11556218 T/G polymorphism of the IL-16 gene was significantly associated with the susceptibility to CRC and GC patients. Both male and female patients carrying the G allele had a significantly higher risk for developing CRC and GC compared with individuals carrying the T allele. Alternatively, women carrying the T allele (rs4072111 C/T) showed a decreased risk for CRC and GC compared with individuals carrying the C allele. In patients with CRC or GC, IL-16 serum levels were significantly higher than those in the healthy controls, although no significant association between IL-16 polymorphisms and serum levels of IL-16 was observed. Our data indicate that IL-16 polymorphisms may contribute to CRC and GC susceptibility.

Association between pri-miR-218 polymorphism and risk of hepatocellular carcinoma in a Han Chinese population.

MicroRNAs are noncoding RNA molecules of 18-25 nucleotides that regulate gene expression at the post-transcriptional level. The aim of this study was to investigate whether pri-miR-218 rs11134527 A/G polymorphism influences the risk of hepatocellular carcinoma (HCC) or not. pri-miR-218 rs11134527 A/G was genotyped in 302 HCC patients and 513 control subjects using the polymerase chain reaction-restriction fragment length polymorphism assay. The AG genotype of pri-miR-218 rs11134527 A/G was associated with family history (p=0.018, odds ratio [OR]=2.96, 95% confidence interval [CI]: 1.16-7.56) and elevated serum α-fetoprotein (serum alpha-fetoprotein [AFP]) levels (≥20 ng/mL; p=0.009, OR=1.92, 95% CI: 1.17-3.14) in HCC patients. These findings suggested that the AG genotype of pri-miR-218 rs11134527 might relate to genetic predisposition and be involved in regulating the expression of AFP in Chinese HCC patients.

Association Between Single-Nucleotide Polymorphisms in Pre-miRNAs and the Risk of Asthma in a Chinese Population

Single-nucleotide polymorphisms (SNPs) in pre-miRNAs may alter microRNA (miRNA) expression levels or processing and contribute to susceptibility to a wide range of diseases. We investigated the correlation between four SNPs (rs11614913, rs3746444, rs2910164, and rs229283) in pre-miRNAs and the risk of asthma in 220 asthma patients and 540 controls using polymerase chain reaction-restriction fragment length polymorphism methodology and DNA-sequencing. There were significant differences in the genotype and allelic distribution of rs2910164G/C and rs2292832C/T polymorphisms among cases and controls. The CC genotype and C allele of rs2910164G/C were significantly associated with a decreased risk of asthma (CC vs. GG, odds ratio [OR] = 0.51, 95% confidence interval [CI]: 0.31-0.82; C vs. G, OR = 0.74, 95% CI: 0.59-0.93). Similarly, the TT genotype and T allele of rs2292832C/T were significantly associated with a decreased risk of asthma (TT vs. CC, OR = 0.56, 95% CI: 0.33-0.95; T vs. C, OR = 0.71, 95% CI: 0.53-0.95). However, no significant association between the other two polymorphisms (i.e., rs11614913C/T and rs3746444C/T) and the risk of asthma was observed. Our data indicate that rs2910164G/C and rs2292832C/T may play a role in the development of asthma.

Association of Matrix Metalloproteinases 1, 7, and 9 Gene Polymorphisms with Genetic Susceptibility to Colorectal Carcinoma in a Han Chinese Population

Matrix metalloproteinases (MMPs) play an important role in colorectal cancer (CRC). Accumulated evidence suggests an association between MMP-1, MMP-7, and MMP-9 functional gene polymorphisms with several tumors. The aim of this study was to investigate the association of single-nucleotide polymorphism (SNP) at MMP-1 16071G/2G, MMP-7 181A/G, and MMP-9 279R/Q genes with CRC in the southwest Chinese Han population. The study used 237 CRC patients and 252 normal control matched by age and sex from Sichuan province in China. Samples were genotyped using both polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. We found significant differences in the genotype and allele frequency of MMP-9 279 R/Q between the case and control group. Individuals who carried MMP-9 279 R allele were more susceptible to CRC (odds ratio = 1.737, 95% confidence interval = 1.323-2.281, p < 0.001). Moreover, the RR genotype of MMP-9 279 R/Q was associated with an increased risk of CRC compared with the QQ genotype (odds ratio = 2.213, 95% confidence interval = 1.248-3.926, p = 0.006). However, there were no significant differences in the genotype and allele frequency of the MMP-1 16071G/2G and MMP-7 181 A/G between the case and control group, and the latter may be due to lower minor allele frequency. The MMP-9 279R/Q alleles and genotypes may be associated with the risk of CRC in Han Chinese.

Association of tumor necrosis factor gene polymorphisms with susceptibility to dilated cardiomyopathy in a Han Chinese population.

Tumor necrosis factor (TNF) is an immunomodulatory cytokine that plays an important role in many inflammatory and autoimmune diseases. We investigated the correlation between single-nucleotide polymorphisms of the TNF gene [i.e., TNF-α (308), TNF-α (857), TNF-α (863), TNF-α (1031), and TNF-ß (+252)] and dilated cardiomyopathy (DCM). A total of 110 DCM patients and 110 control subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism and DNA-sequencing assay. GA=AA genotypes of TNF-α (308) were significantly associated with increased risk of DCM compared with GG genotype (odds ratio[OR]=1.92; 95% confidence intervals [CI], 1.05-3.52). Similarly, GA=AA of TNF-ß (+252) was significantly associated with increased risk of DCM compared with GG genotype (OR=1.97; 95% CI, 1.14-3.38). Additionally, A allele of TNF-α (-308) and TNF-ß (+252) was associated with a 1.76-fold increased risk of DCM compared with G allele (OR=1.76; 95% CI, 1.05-2.95 and OR=1.79; 95% CI, 1.22-2.63, respectively). However,no association between DCM and TNF-α (857), TNF-α (1031), and TNF-α (863) was observed. TNF gene polymorphisms may be associated with risk of DCM.

A Functional Polymorphism in the Promoter of MiR-143/145 Is Associated With the Risk of Cervical Squamous Cell Carcinoma in Chinese Women: A Case-Control Study.

Abstract MiR-143/145 is down-regulated in cervical cancer, which may serve as a tumor suppressor by targeting KRAS and Ras-responsive element-binding protein (RREB1). Activated KRAS leads to down-regulation of miR-143/145 transcription in a RREB1-dependent manner, establishing a miR-143/145-KRAS-RREB1 feedback loop. A polymorphism rs4705343C/T in the promoter of miR-143/145 might influence the binding of TATA-binding protein. We hypothesized that the miR-143/145 rs4705343 and KRAS rs712 may be related to the occurrence of cervical squamous cell carcinoma (CSCC). In this study, we genotyped the 2 polymorphisms in 415 patients with CSCC and 504 controls using polymerase chain reaction–restriction fragment length polymorphism. The promoter activities were measured by the Dual-Luciferase Reporter Assay System. We found that the rs4705343TC genotype was associated with an increased risk of CSCC (adjusted odds ratio [OR] = 1.37; 95% confidence interval [CI], 1.05–1.80). The significantly increased association was also observed in a dominant genetic model (adjusted OR = 1.32; 95% CI, 1.01–1.72). Combined analysis showed that individuals carrying the genotypes of rs4705343 TC/CC and rs712GT/TT had a 1.47-fold increased risk of CSCC (adjusted OR = 1.47; 95% CI, 1.01–2.15). By using multifactor dimensionality reduction software method, we identified a significant interaction between the miR-143/145 rs4705343 and KRAS rs712. Dual-Luciferase Reporter Assay showed that the luciferase activity was significantly lower in cells transfected with the rs4705343C allele than that of the rs4705343T allele. These findings indicate that miR-143/145 rs4705343 and KRAS rs712 may contribute to the etiology of CSCC in Chinese women.

Association of ADAM33 Polymorphisms and Susceptibility to Psoriasis

Psoriasis (PS) is a common hyperproliferative and chronic inflammatory disease of the skin, which involves both genetic and environmental factors. The A disintegrin and metalloproteinase 33 (ADAM33) gene, located on chromosome 20p13, has recently been identified as an asthma-susceptibility gene by positional cloning. Recently, it has been reported that ADAM33 contributed to PS risk in the French population and white North Americans. To observe the relationship between ADAM33 gene and PS, a case-control study was conducted in a Han Chinese population. Three polymorphic sites (T1, T2, and V4) were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis in 106 patients with PS and 125 healthy controls. We observed a decreased frequency in the CG genotype and GG genotype of ADAM33 rs2787094 (V4) in cases compared with controls (p = 0.045, odds ratio = 0.461, 95% confidence interval = 0.215-0.992, and p = 0.044, odds ratio = 0.447, 95% confidence interval = 0.203-0.987, respectively). Our data suggest that the ADAM33 gene may be associated with PS risk in the Chinese population.

Genetic diversity of 21 autosomal STR loci in the Han population from Sichuan province, Southwest China

Exploration of the ethnic origin and genetic differentiation of 56 Chinese officially recognized nationalities populations played a fundamental role in the research field of population genetics, forensic science, linguistics, anthropology, and archaeology. In the present study, population data of 21 autosomal STR loci (CSF1PO, D10S1248, D12S391, D13S317, D16S539, D18S51, D19S433, D21S11, D2S1338, D2S441, D3S1358, D5S818, D6S1043, D7S820, D8S1179, FGA, Penta D, Penta E, TH01, TPOX, and vWA) included in the AGCU EX22 kit in 2793 Southwest Han Chinese individuals was obtained and population genetic relationships among 28 Chinese populations were investigated. Our study indicated that the twenty-one autosomal STRs are highly polymorphic in the Sichuan Han population and can be used as a powerful tool in the routine forensic usage. MDS and phylogenetic analysis suggested that the Sichuan Han population kept a close genetic relationship with the southwest populations.

Mutational analysis of 33 autosomal short tandem repeat (STR) loci in southwest Chinese Han population based on trio parentage testing

Mutation rates and 95% CI of 33 short tandem repeat (STR) loci (D1S2142, D2S1338, D2S441, D3S1358, D3S1754, D5S818, D6S1043, D7S3048, D7S820, D8S1132, D8S1179, D10S1248, D11S2368, D12S391, D13S1492, D13S317, D13S325, D14S306, D15S659, D16S539, D18S1364, D18S51, D19S433, D20S161, D21S11, D22GATA198B05, CSF1PO, FGA, Penta D, Penta E, TH01, TPOX, and vWA) were investigated through more than 424,000 parent-child meiotic transfers obtained from 10636 trios parentage testing cases in southwest Chinese Han population. Overall, 297, including 292 single-step, 4 double-step and 1 triple-step mutation events were observed. The average mutation rate was 0.70×10(-3). Most of the locus-specific mutation rates (varied from 0.20×10(-3) to 1.96×10(-3)) were lower than the other datasets (p<0.05). Mutations of 7 loci are reported for the first time. Mutation rates varied with population from different ethnicities and geographical regions. There was no significant difference between mutation expansion and contraction (∼1.04:1). Paternal origin mutations occurred more frequently than maternal origin ones (∼5.02:1). In addition, mutation rates indicated positive correlation with the expected heterozygosity (He) and geometric mean of longest run of perfect repeats (LRPR), respectively. Short alleles showed a trend toward mutation gain while long alleles trended toward mutation loss. A credible forensic dataset for locus-specific mutation rates of 33 loci has been established based upon strict inclusion criteria of large-sized parents/child-trio cases.

The Association Between Interleukin-23 Receptor Gene Polymorphisms and Systemic Lupus Erythematosus

The aim of this study was to investigate single-nucleotide polymorphism of the IL-23R gene and its possible relationship with systemic lupus erythematosus (SLE) in a Chinese population. We examined 139 SLE patients and 168 controls from Sichuan province in China. The genotyping of IL-23R is determined by polymerase chain reaction-restriction fragment length polymorphism. These results indicate that there is no relationship between IL-23R polymorphisms and SLE in a Chinese population. Further studies are still needed to explore the complicated interaction between environmental factors and IL-23R polymorphisms in the risk of SLE, particularly in ethnically different populations. There were no significant differences in the genotype and allele frequencies of rs10889677, rs1884444, and rs7517847 polymorphisms between the patients with SLE and the control group in a Chinese population (for rs10889677: odds ratio [OR] = 1.00, 95% confidence interval [CI] = 0.69-1.45; for rs1884444: OR = 0.96, 95% CI = 0.69-1.33; and for rs7517847: OR = 0.93, 95% CI = 0.67-1.27).