Polymorphisms of fibronectin-1 (rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655) are not associated with bronchopulmonary dysplasia in preterm infants

Molecular and Cellular Biochemistry - Bronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects premature newborns. Many different factors, increasingly genetic, are involved...     

The Association between Four Genetic Variants in MicroRNAs (rs11614913, rs2910164, rs3746444, rs2292832) and Cancer Risk: Evidence from Published Studies

MicroRNAs (miRNAs) participate in diverse biological pathways and may act as either tumor suppressor genes or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNA may contribute to cancer development with changes in the microRNA''s properties and/or maturation. Polymorphisms in miRNAs have been suggested in predisposition to cancer risk; however, accumulated studies have shown inconsistent conslusionss. To further validate determine whether there is any potential association between the four common SNPs (miR-196a2C>T, rs11614913; miR-146aG>C, rs2910164; miR-499A>G, rs3746444; miR-149C>T, rs2292832) and the risk for developing risk, a meta-analysis was performed according to the 40 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the extent of the association. The results demonstrated that the rs11614913TT genotype was significantly associated with a decreased cancer risk, in particular with a decreased risk for colorectal cancer and lung cancer, or for Asian population subgroup. In addition, the rs2910164C allele was associated with decreased risk for esophageal cancer, cervical cancer, prostate cancer, and hepatocellular carcinoma (HCC), in particular in Asian population subgroup. Similarly, the rs3746444G allele was observed as a risk factor for cancers in the Asian population. It is concluded that two SNPs prsent in miRNAs(rs11614913TT, and rs2910164C) may protect against the pathogenesis of some cancers, and that the rs3746444 may increase risk for cancer.     

The CARD9 Polymorphisms rs4077515, rs10870077 and rs10781499 Are Uncoupled from Susceptibility to and Severity of Pulmonary Tuberculosis

Genetic variants in the CARD9 gene predispose to inflammatory disorders and chronic infectious diseases. Tuberculosis (TB), a chronic infectious disease affecting the lung, is lethal in Card9-deficient mice. We hypothesized that polymorphisms in the CARD9 gene influence TB progression and disease-associated lung damage in humans. We tested genotype distributions of the CARD9 polymorphisms rs4077515, rs10781499 and rs10870077 in TB patients and healthy subjects in a Caucasian cohort. SNPs were in linkage disequilibrium and none of the haplotypes was significantly enriched in the TB group. We determined total and differential leukocyte count, erythrocyte sedimentation rate and plasma abundance of cytokines and chemokines as markers for systemic inflammation and scored chest X-rays to assess lung involvement in TB subjects. Most disease parameters segregated independently of the CARD9 haplotypes. In contrast to multifactorial chronic inflammation, selected genetic variants in the CARD9 gene leave host responses apparently unaffected in TB, at least in the population analyzed here.     

Association of obesity with rs1421085 and rs9939609 polymorphisms of FTO gene

The aim of this study is to investigate the genetic influence of polymorphisms in fat mass and obesity associated (FTO) gene on a sample of obese subjects and controls. Obesity is an epidemic all over the world. Several polymorphisms in the first intron of FTO gene have been associated with common forms of human obesity. In this research rs1421085 and rs9939609 polymorphisms of FTO gene were genotyped in 190 obese patients with a BMI ≥30 kg/m² (Body Mass Index) and 97 healthy controls with a BMI of 18.5–24.9. Genotyping of SNPs was performed by real-time polymerase chain reaction. Body composition was established with bioelectric impedance analysis. Waist-to-hip ratio was determined for all participants. There were no significant differences (P > 0.05) between obese cases and controls in terms of genotype frequencies of rs1421085 and rs9939609 polymorphisms in our study. Also there were no significant correlations between genotypes and obesity related (anthropometric-body composition) parameters (P > 0.05).     

Characteristic of the genetic variability of four polymorphic variants (rs2069705, rs17880053, rs11126176, and rs804271) in representative samples of indigenous and arrived populations of Siberia

Russian Journal of Genetics - The variability of potentially important functional polymorphic variants rs2069705 (5'UTR of the IFNG gene), rs17880053 (near 5'UTR of the IFNGR2), rs11126176...     

Leukocyte Telomere Length-Related rs621559 and rs398652 Genetic Variants Influence Risk of HBV-Related Hepatocellular Carcinoma

Recent genome-wide association studies (GWAS) have identified eleven leukocyte telomere length (LTL)-related single nucleotide polymorphisms (SNPs). Since LTL has been associated with risk of many malignancies, LTL-related SNPs may contribute to cancer susceptibility. To test this hypothesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we genotyped these eleven LTL-related SNPs in a case-control set including 1186 HBV-related HCC cases, 508 chronic HBV carriers and 1308 healthy controls at the discovery stage. The associations of HCC risk with these SNPs were further confirmed in an independent case-control set. We found that 1p34.2 rs621559 and 14q21 rs398652 were significantly associated with HBV-related HCC risk (both P<0.005 after Bonferroni corrections). There was no significant difference of either rs621559 or rs398652 genotypes between chronic HBV carriers and healthy controls, demonstrating that the association was not due to predisposition to HBV infection. In the pooled analyses (1806 HBV-related HCC cases and 1954 controls), we observed a decreased HCC risk, 0.72-times, associated with the 1p34.2 rs621559 AA genotype compared to the GG genotype (P = 1.6×10⁻⁶). Additionally, there was an increased HCC risk, 1.27-fold, associated with the rs398652 GG genotype (P = 3.3×10⁻⁶). A statistical joint effect between the rs621559 GG and rs398652 GG genotypes may exist in elevating risk of HBV-related HCC. We show, for the first time, that rs398652 and rs621559 might be marker genetic variants for risk of HBV-related HCC in the Chinese population.     

PLCE1基因及rs2274223和rs3765524单体型的克隆与表达

目的：克隆人PLCE1基因,构建PLCE1 rs2274223和rs3765524 GT（PLCE1 Minor）和AC（PLCE1 Major）单体型真核表达重组载体,研究PLCE1基因多态性及单体型与基因表达的相关性。方法：利用重叠延伸PCR、In-Fusion技术构建PLCE1真核表达载体;基于同源重组的双点突变技术改造目的基因;利用基因转染、实时定量PCR和蛋白印迹等技术实现PLCE1表达载体在真核细胞中的过表达及表达水平的鉴定。结果：成功扩增并获得了全长6 927bp的人PLCE1 cDNA并经过DNA测序证实,与NCBI数据库PLCE1参考序列（NM_016341）比较,发现编码区3 554~3 572bp处存在18bp连续碱基插入,其余序列基本匹配。成功构建了PLCE1 Minor和PLCE1 Major两种单体型重组真核表达载体,转染细胞揭示PLCE1 Minor型的mRNA转录和蛋白质表达水平均高于Major型。结论：发现了一种新的PLCE1 mRNA转录本,成功构建了2种单体型真核表达载体;发现PLCE1 rs2274223G-rs3765524T单体型能够促进自身mRNA和蛋白质表达,为进一步揭示PLCE1 SNPs与癌症易感性的关系奠定了基础。     

Linkage disequilibrium and haplotypes of the rs1042522, rs1625895, and rs1787862 markers of TP53 in patients with diffuse large B-cell lymphoma

The association of the rs1042522, rs17878362, and rs1625895 polymorphisms of TP53 with risk of non-Hodgkin’s lymphoma (NHL) has not been studied in full detail. NHL has many variants, and each individual polymorphism exerts only a minor effect, requiring the polymorphisms to be studied for particular histological subtypes of lymophomas and as components of haplotype groups. The objective of this work was to analyze the frequencies and linkage disequilibrium for rs1042522, rs1625895, and rs17878362 and their combined haplotype in patients with diffuse large B-cell lymphoma (DLBCL) and control subjects. Differences in linkage disequilibrium structure were observed for rs17878362, rs1042522, and rs1625895 in the Siberian population. The haplotype proved to be more informative than the individual TP53 polymorphisms in a case-control association analysis in DLBCL. Haplotype wArgG was associated with predisposition to DLBCL, while haplotypes wProG and dupProG were found to exert a protective effect. The effect of the haplotype at three TP53 polymorphisms was observed to vary depending on their homozygous or heterozygous state.     

Effects of PRSS1-PRSS2 rs10273639, CLDN2 rs7057398 and MORC4 rs12688220 polymorphisms on individual susceptibility to pancreatitis: A meta-analysis

BackgroundGenetic association studies regarding relationship between PRSS1-PRSS2 rs10273639/CLDN2 rs7057398/MORC4 rs12688220 polymorphisms and pancreatitis yielded conflicting results. We performed this meta-analysis to explore associations between these polymorphisms and pancreatitis in a larger pooled population.MethodsA systematic search of the literature was conducted for eligible studies. We used Review Manager to conduct statistical analyses.ResultsFifteen studies were included in this meta-analysis. The results of pooled analyses showed that CLDN2 rs7057398, MORC4 rs12688220 and PRSS1-PRSS2 rs10273639 polymorphisms were all significantly associated with susceptibility to acute pancreatitis in Caucasians. Moreover, MORC4 rs12688220 and PRSS1-PRSS2 rs10273639 polymorphisms were also significantly associated with susceptibility to chronic pancreatitis in Asians.ConclusionsOur findings suggested that rs7057398, rs12688220 and rs10273639 polymorphisms could be used to identify individuals at an elevated susceptibility to acute pancreatitis in Caucasians. Moreover, rs12688220 and rs10273639 polymorphisms could be used to identify individuals at an elevated susceptibility chronic pancreatitis in Asians.     

Association of C-reactive protein (CRP) rs1205 and rs2808630 variants and risk of cancer

The correlation between rs1205, rs2808630 variants of C-reactive protein (CRP) gene and susceptibility of cancer has been assessed previously, but with conflicting results. We adopted odds ratios (ORs) with 95% confidence intervals (CIs), in silico tools and enzyme-linked immunosorbent assay (ELISA) analysis to evaluate this association. Totally, 10,614 cancer subjects and 33,294 controls were involved in the pooled analysis. When all the studies were pooled, no significant correlation was indicated between the two variants and cancer risk. However, in stratification analysis by ethnicity, we found that CRP rs1205 C>T polymorphism was associated with an elevated risk of cancer in Asians (T-allele vs. C-allele, OR = 1.20, 95% CI = 1.06–1.36, p_{heterogeneity} = .226; TT vs. CC, OR = 1.48, 95% CI = 1.14–1.93, p_{heterogeneity} = .089). Similar findings were observed for rs2808630 variant. In silico tools showed that lung adenocarcinoma participants with high CRP expression may have shorter overall survival time than low expression group. ELISA analysis indicated that CRP expression in prostate adenocarcinoma subjects with TT + TC genotypes was statistically higher than in those with CC genotypes. CRP rs1205 C>T and rs2808630 T>C polymorphism may be associated with cancer risk, especially for Asians.     

Lipoprotein Lipase SNPs rs13702 and rs301 Correlate with Clinical Outcome in Chronic Lymphocytic Leukemia Patients

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and is characterized by a heterogeneous clinical course. This variability in clinical course has spiked the search for prognostic markers able to predict patient evolution at the moment of diagnosis. Markers demonstrated to be of value are the mutation status of the immunoglobulin heavy chain variable region genes (IGHV) and lipoprotein lipase (LPL) expression. High LPL mRNA expression has been associated with short treatment free (TFS) and decreased overall survival (OS) in CLL. The LPL SNPs rs301 (T<C), rs328 (C<G) and rs13702 (T<C) have been associated with various metabolic disorders, but the association with CLL evolution is unknown. Here, in a cohort of 248 patients, we show that patients with the LPL SNP rs13702 wild-type T/T genotype had significantly shorter OS than patients with C/C and T/C genotypes (median time until CLL related death: 90 and 156 months respectively, p=0.008). The same was observed for LPL SNP rs301 (median time until CLL related death T/T: 102 and C/C, T/C: 144 months, p=0.03). Both SNPs rs301 and rs13702 were significantly associated with each other and notably, no association was found between IGHV status and presence of the SNP genotypes, indicating that these LPL SNPs are reliable prognostic markers that could add extra prognostic and predictive information to classical markers and help to improve the management of CLL.     

Interleukin-10 rs2227307 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock

Despite major improvements in its treatment and diagnosis, sepsis is still a leading cause of death and admittance to the intensive care unit (ICU). Failure to identify patients at high risk of developing septic shock contributes to an increase in the sepsis burden and rapid molecular tests are currently the most promising avenue to aid in patient risk determination and therapeutic anticipation. The primary goal of this study was to evaluate the genetic susceptibility that affects sepsis outcome in 72 sepsis patients admitted to the ICU. Seven polymorphisms were genotyped in key inflammatory response genes in sepsis, including tumour necrosis factor-α, interlelukin (IL)-1β, IL-10, IL-8, Toll-like receptor 4, CXCR1 and CXCR2. The primary finding showed that patients who were homozygous for the major A allele in IL-10 rs1800896 had almost five times higher chance to develop septic shock compared to heterozygotes. Similarly, selected clinical features and CXCR2 rs1126579 single nucleotide polymorphisms modulated septic shock susceptibility without affecting survival. These data support the hypothesis that molecular testing has clinical usefulness to improve sepsis prognostic models. Therefore, enrichment of the ICU portfolio by including these biomarkers will aid in the early identification of sepsis patients who may develop septic shock.     

The Functional TP53 rs1042522 and MDM4 rs4245739 Genetic Variants Contribute to Non-Hodgkin Lymphoma Risk

As a heterogeneous kind of malignances, Non-Hodgkin lymphoma (NHL) is the most common hematologic cancer worldwide with the significantly increased morbidity in China. Accumulated evidences demonstrated that oncoprotein MDM4 plays a crucial role in the TP53 tumor suppressor signaling pathway. An rs4245739 A>C polymorphism locating in the MDM4 3′-untranslated region creates a miR-191 target site and results in allele-specific MDM4 expression. In this study, we examined the association between this polymorphism as well as the TP53 Arg72Pro (rs1042522 G>C) genetic variant and Non-Hodgkin Lymphoma (NHL) risk in a Chinese Han population. Genotypes were determined in 200 NHL cases and 400 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. We found significantly increased NHL risk among carriers of the TP53 72Pro allele compared with those with the 72Arg allele (P = 0.002 for the Pro/Pro genotype). We also observed a significantly decreased NHL risks among carriers of the MDM4 rs4245739 C allele compared with those with the A allele in Chinese (P = 0.014 for the AC genotype). Stratified analyses revealed the associations between these SNPs and NHL risk are especially noteworthy in young or male individuals. Additionally, the associations are much pronounced in NHL patients with B-cell lymphomas or grade 3 or 4 disease. Our results indicate that the TP53 Arg72Pro and the MDM4 rs4245739 polymorphisms contribute to NHL susceptibility and support the hypothesis that genetic variants in the TP53 pathway genes can act as important modifiers of NHL risk.     

Association of genetic variants rs641153 (CFB), rs2230199 (C3), and rs1410996 (CFH) with age-related macular degeneration in a Brazilian population

This study aimed to investigate the association among genetic variants of the complement pathway CFB R32Q (rs641153), C3 R102G (rs2230199), and CFH (rs1410996) with age-related macular degeneration (AMD) in a sample of the Brazilian population. In a case-control study, 484 AMD patients were classified according to the clinical age-related maculopathy grading system (CARMS) and compared to 479 unrelated controls. The genetic variants rs1410996 of complement H (CFH), rs641153 of complement factor B (CFB), and rs2230199 of complement 3 (C3) were evaluated through polymerase chain reaction (PCR) and direct sequencing. The associations between single nucleotide polymorphisms (SNPs) and AMD, adjusted by age, were assessed by using logistic regression models. A statistically significant association was observed between AMD risk and rs2230199 variant with an OR of 2.01 (P  = 0.0002) for CG individuals compared to CC individuals. Regarding the comparison of advanced AMD versus the control group, the OR was 2.12 (P = 0.0036) for GG versus AA genotypes for rs1410996 variant. Similarly, the OR for rs2230199 polymorphism was 2.3034 (P  = 5.47^e-05) when comparing CG individuals to CC carriers. In contrast, the rs641153 variant showed a significant protective effect against advanced AMD for GA versus GG genotype (OR = 0.4406; P  = 0.0019). When comparing wet AMD versus controls, a significant association was detected for rs1410996 variant (OR = 2.16; P  = 0.0039) comparing carriers of the homozygous GG versus AA genotype, as well as in the comparisons of GG (OR = 3.0713; P  = 0.0046) and CG genotypes (OR = 2.2249; P  = 0.0002) versus CC genotype for rs2230199 variant, respectively. The rs641153 variant granted a significant protective effect against wet AMD for GA versus GG genotypes (OR = 0.4601; P  = 0.0044). Our study confirmed the risk association between rs2230199 and rs1410996 variants and AMD, and the protective role against AMD for rs641153 variant.     

PSCA gene variants (rs2294008 and rs2978974) confer increased susceptibility of gallbladder carcinoma in females

Background and aim

PSCA is a tissue specific tumor suppressor or oncogene which has been found to be associated with several human tumors including gallbladder cancer. It is considered to be involved in the cell-proliferation inhibition and/or cell-death induction activity. Therefore, we aimed to investigate the role of PSCA gene polymorphisms in gallbladder cancer risk in North Indian population.

Methodology

A total of 405 gallbladder cancer patients and 247 healthy controls were included in the case–control study for risk prediction. We examined the association of two functional SNPs, rs2294008 and rs2978974 in PSCA gene by genotyping using Taqman allelic discrimination assays. Statistical analysis was done using SPSS software, version 17. Linkage disequilibrium and haplotype analysis was done with the help of SNPstats software. FDR test was used to correct for multiple comparisons.

Results

No significant associations of rs2294008 and rs2978974 genetic variants of the PSCA gene were found with GBC risk at allele, genotype or haplotype levels. Stratifying the subjects on the basis of gallstone also did not show any significant result. However, on gender stratification, we found a significant association of T_rs2294008-G_rs2978974 haplotype with higher risk of GBC in females (FDR Pcorr = 0.021, OR = 1.6). In contrary, T_rs2294008-A _rs2978974 haplotype conferred significant lower risk in males (FDR Pcorr = 0.013; OR = 0.25).

Conclusions

These findings suggest that PSCA genetic variants may have a significant effect on GBC susceptibility in a gender specific manner.