Genetic variation in miR-100 rs1834306 is associated with decreased risk for esophageal squamous cell carcinoma in Kazakh patients in northwest China

MicroRNAs (miRNAs) are a family of small noncoding RNAs that act as oncogenes and tumor suppressors. Single nucleotide polymorphisms (SNPs) in miRNAs may be associated with changes in phenotype and function. The aim of this study was to verify whether genetic variations in candidate microRNA (miRNA or miR) genes could contribute to esophageal squamous cell carcinoma (ESCC) susceptibility. A case-control study in 248 Kazakh patients with ESCC and 300 frequency matched control subjects was carried out to examine the potential association of six miRNA (miR-100 rs1834306, miR-34b/c rs4938723, miR-375 rs6715345, miR-146a rs2910164, miR-423 rs6505162 and miR-373 rs12983273) polymorphisms with risk of ESCC. We found that miR-100 rs1834306 T>C polymorphism was associated with a significant decreased risk of ESCC. In the recessive model, when the miR-100 rs1834306 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significant decreased risk for ESCC (adjusted OR=0.495, 95% CI: 0.349-0.702, P=8.05×10^-5). In the dominant model, when the miR-100 rs1834306 TT genotypes was used as the reference group, the TC/CC genotype were associated with a borderline statistically decreased risk for ESCC (adjusted OR=0.665, 95% CI: 0.430-1.031, P=0.067). In addition, the miR-100 rs1834306 C allele in the Kazakh population was significantly associated with decreased risk of ESCC (OR=0.609, 95% CI: 0.48-0.78, P=8.37×10^-5). These findings indicated that functional polymorphism miR-100 rs1834306 C>T might contribute to decreased ESCC risk.     

Scavenger Receptor Class B Type 1 Gene rs5888 Single Nucleotide Polymorphism and the Risk of Coronary Artery Disease and Ischemic Stroke: A Case-Control Study

Background: Our previous studies have showed that the rs5888 single nucleotide polymorphism (SNP) in Scavenger receptor class B type 1 (SCARB1) gene is associated with serum lipid levels in the general Chinese populations. The present study was undertaken to detect the associations between rs5888 SNP and the risk of coronary artery disease (CAD) and ischemic stroke (IS).Methods: A total of 1,716 unrelated subjects (CAD, 601; IS, 533; and healthy controls, 582) were included in this study. Genotyping of the rs5888 SNP were determined by polymerase chain reaction and restriction fragment length polymorphism.Results: The genotypic frequencies of SCARB1 rs5888 SNP were different between CAD patients and controls, the subjects with TT genotype had high risk of CAD (OR = 1.76, P = 0.038 for TT vs. CC; and OR = 1.75, P = 0.036 for TT vs. CC/CT). There was no significant association between genotypes and the risk of IS. Further analysis showed that the subjects with TT genotype in the total population had lower levels of high-density lipoprotein cholesterol than the subjects with CC/CT genotypes (P < 0.05), the subjects with TT genotype in controls but not in CAD or IS patients had higher levels of serum LDL-C and ApoB than those with CC genotype (P < 0.05 for each).Conclusions: The present study suggests that the SCARB1 rs5888 SNP influences serum lipid levels, and is associated with the risk of CAD.     

Lack of association of polymorphism in miRNA-196a2 with Parkinson's disease risk in a Chinese population

MicroRNAs (miRNAs) are a new class of non-protein coding RNA molecules, which participate in diverse biological pathways. We hypothesized that miRNA-196a2 polymorphism is associated with the risk of Parkinson's disease (PD) in a Chinese population. In a case-control study of 549 PD patients and 736 control subjects frequency matched by age and gender, we genotyped the single-nucleotide polymorphism (SNP) rs11614913 (T>C) in miRNA-196a2, whose target mRNA was alpha-synuclein, and assessed its association with risk of PD by TaqMan Genotyping method. No association was found for the miR-196a2 rs11614913 CT/CC genotype (odds ratio (OR), 0.879, 95% confidence interval (CI), 0.681-1.135 for CT genotype; OR, 1.085, 95% CI, 0.793-1.484 for CC genotype) with risk of PD, compared with the TT genotype. These results suggest that SNP rs11614913 in miRNA-196a2 may not contribute to the susceptibility to PD.     

HTRA1 Variants and the Interaction with Smoking Confer the Genetic Susceptibility to Ischemic Stroke

High temperature requirement protein A1 (HtrA1) was identified as the causative gene of autosomal recessive arteriopathy and associated with lacunar ischemic stroke (IS) in European. This study aimed at evaluating the association of HTRA1 with IS and four tagging single-nucleotide polymorphisms (SNPs) were genotyped in a cohort of 4,098 Chinese. The mRNA level of HTRA1 in 72 IS cases and 72 hypertension controls were measured and compared. In whole population, SNP rs2268350 (C>T) was significantly associated with IS incidence (P=0.034). Stratification analysis observed significant association of rs2268350 in male, smoking and drinking populations, rs2672587 (C>G) in smoking and nonsmoking populations and rs3793917 (C>G) in smoking, nonsmoking and nondrinking populations with stroke respectively (P<0.05). The additive interaction and multiplicative interaction between rs2268350 and smoking were both of significant (P<0.05) after adjustment for the covariates. There was a cumulated risk of IS among genotypes of rs3793917 (P=0.009) and rs2672587 (P=0.047) in smoking population. The mRNA level of HTRA1 in non-smokers with rs2268350 CC was significantly higher than smokers with rs2268350 CT/TT (P=0.046) in IS cases. Our findings support that HTRA1 confers the genetic susceptibility to IS and smoking might modify the genetic effect of HTRA1 on IS by suppressing HTRA1 mRNA expression.     

Methylenetetrahydrofolate Reductase C667T Polymorphism is Associated with Increased Risk of Coronary Artery Disease in a Chinese Population

Coronary artery disease (CAD) is a complex disease resulting from a combination of environmental and genetic factors. We hypothesized that polymorphisms in methylenetetrahydrofolate reductase (MTHFR) rs1801133 C/T, matrix metalloproteinases (MMPs)‐2, tumour necrosis factor (TNF)‐α, macrophage migration inhibitory factor (MIF) rs755622 G/C and cyclin D1 (CCND1) rs678653 G/C contribute to CAD susceptibility. We examined the association between the five polymorphisms and the risk of CAD in a Chinese population of 435 CAD patients and 480 controls. Genotyping was performed using matrix‐assisted laser desorption ionization/time‐of‐flight mass spectrometry (MALDI/TOF MS). When the MTHFR rs1801133 CC homozygote genotype was used as the reference group, the TT or CT/TT genotypes were associated with a significantly increased risk for CAD. The CT heterozygote genotype was not associated with the risk for CAD. Logistic regression analyses revealed that MMP‐2 rs243865 C/T, TNF‐α rs1800629 A/G, MIF rs755622 G/C and CCND1 rs678653 G/C polymorphisms were not associated with the risk of CAD. These findings suggest that the MTHFR rs1801133 C/T polymorphism is associated with CAD development. Future larger studies with other ethnic populations are required to confirm current findings.     

Association of two polymorphisms in the FADS1/FADS2 gene cluster and the risk of coronary artery disease and ischemic stroke

Little is known about the association of the FADS1/FADS2 SNPs and serum lipid levels and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese southern population. The present study aimed to determine such association in the Chinese southern population. A total of 1,669 unrelated subjects (CAD, 534; IS, 553; and healthy controls, 582) were recruited in the study. Genotypes of the FADS1 rs174546 SNP and the FADS2 rs174601 SNP were determined by the SNaPshot Multiplex Kit. The T allele and TT genotype frequencies of the two SNPs were predominant in our study population. The T alleles were associated with increased risk of CAD and IS. Correspondingly, the C alleles were associated with reduced risk of CAD and IS. Haplotype analyses showed that the haplotype of T-T (rs174546-rs174601) was associated with an increased risk for IS, and the haplotype of C-C (rs174546-rs174601) was associated with a reduced risk for CAD and IS. The two SNPs were likely to influence serum lipid levels. The T allele carriers of the two SNPs and rs174601 TT genotype were associated with decreased serum HDL-C and ApoAI levels in the patient groups and with an increased risk of CAD and IS. The present study suggests that the FADS1 rs174546 SNP and the FADS2 rs174601 SNP are associated with the risk of CAD and IS, and are likely to influence serum lipid levels. However, further functional studies are needed to clarify how the two SNPs actually affect serum lipid levels and the risk of CAD and IS.     

Gene-gene interaction in folate-related genes and risk of neural tube defects in a UK population

Objective: To investigate the contribution of polymorphic variation in genes involved in the folate-dependent homocysteine pathway in the aetiology of neural tube defects (NTD).

Design: Case-control association study.

Subjects: A total of 530 individuals from families affected by NTD, 645 maternal controls, and 602 healthy newborn controls from the northern UK.

Main outcome measures: Seven polymorphisms in six genes coding for proteins in the folate-dependent homocysteine pathway (MTHFR 677C→T, MTHFR 1298A→C, MTRR 66A→G, SHMT 1420C→T, CßS 844ins68, GCPII 1561C→T, RFC-1 80G→A). The impact of each polymorphism and the effect of gene–gene interactions (epistasis) upon risk of NTD were assessed using logistic regression analysis.

Results: The MTHFR 677C→T polymorphism was shown to represent a risk factor in NTD cases (CC v CT+TT odds ratio (OR) 2.03 [95% confidence interval (CI) 1.09, 3.79] p = 0.025) and the MTRR 66A→G polymorphism was shown to exert a protective effect in NTD cases (AA v AG+GG OR 0.31 [95% CI 0.10, 0.94] p = 0.04). When statistical tests for interaction were conducted, three genotype combinations in cases (MTRR/GCPII; MTHFR 677/CßS; MTHFR 677/MTRR) and one combination in case mothers (CßS/RFC-1) were shown to elevate NTD risk. Maternal–fetal interaction was also detected when offspring carried the MTHFR 677C→T variant and mothers carried the MTRR 66A→G variant, resulting in a significantly elevated risk of NTD.

Conclusion: Both independent genetic effects and gene–gene interaction were observed in relation to NTD risk. Multi-locus rather than single locus analysis might be preferable to gain an accurate assessment of genetic susceptibility to NTD.

     

Association between E-cadherin (CDH1) polymorphisms and pancreatic cancer risk in Han Chinese population

This study was designed to investigate the associations between E-cadherin (CDH1) gene polymorphisms and pancreatic cancer (PC) risk predisposition. We undertook a case-control study to analyze three E-cadherin polymorphisms (+54T>C, -160C>A and -347G→GA) in an Han Chinese population, by extraction of genomic DNA from the peripheral blood of 368 patients with PC and 376 control participants and performed E-cadherin genotyping using DNA sequencing. Overall, no statistically significant association was observed in +54T>C. Nevertheless, -347G→GA genotype was at increased risk of PC (P=0.022; odds ratio (OR) =1.128, CI 95%: 1.017-1.251). Furthermore, -347GA/GA genotype pancreatic cancers were more significantly common in cases of advanced T stage, lymph node metastasis and clinical pathological stage than G or G/GA genotypes PC. However, -160C>A genotype demonstrated a protective effect in PCs (P=0.017; OR=0.883, CI 95%: 0.798-0.977). In conclusion, polymorphism in -347G→GA was observed to be associated with susceptibility of PC. However, -160C>A polymorphism indicated to play a protective role in susceptibility to PC. Nevertheless, further investigation with a larger sample size is needed to support our results.     

广西人群miRNA-107基因多态性分布特征及其与血脂的关系

目的探讨miR-107基因单核苷酸多态性(SNP)位点rs2296616 C/T在广西地区健康人群中的分布特点,对比其在不同种族间基因型及等位基因频率分布的差异,并进一步探讨rs2296616 C/T位点单核苷酸多态性(SNP)与血脂水平的相关性。方法采用多重单碱基延伸SNP分型技术(multiplex SNa Pshot)和DNA测序法,检测372例广西健康人rs2296616 C/T位点的多态性,用7600生化仪检测其血脂相关指标,并用统计学方法分别比较rs2296616C/T位点多态性在各种族人群间的分布差异及不同基因型间的血脂水平差异。结果广西人群miR-107基因rs2296616 C/T位点存在TT(91.1%)和CT(8.9%)两种基因型及T(95.6%)和C(4.4%)两种等位基因。该位点的基因型和等位基因型频率在广西人群不同性别间的比较,差异无统计学意义(P>0.05)。其基因型和等位基因频率与人类基因组单体型图(Hap Map)所公布的欧洲人、日本人、非洲人、印第安人和墨西哥人分型数据相比较,差异均有统计学意义(P<0.05),但与北京汉族人群比较,差异无统计学意义(P>0.05)。rs2296616 C/T位点两种基因型人群血脂之间比较,携带TT基因型人群的高密度脂蛋白胆固醇(HDL-C)与CT组比较,差异具有统计学意义(P<0.05)。结论广西人群miR-107基因rs2296616 C/T位点多态性与其他种族人群之间比较存在不同程度的差异;rs2296616 C/T位点多态性与HDL-C水平高低有关。     

Gene-gene interactions among CX3CL1, LEPR and IL-6 related to coronary artery disease in Chinese Han population

Objective: The purpose of this study was to investigate the impact of the interactions among CX3CL1 (rs170364 and rs614230), LEPR (rs6700896), and IL-6 (rs2066992) polymorphisms on the risk of coronary artery disease (CAD) in Chinese Han population. Methods: 120 CAD patients and 109 healthy controls were enrolled in the study. Polymerase chain reaction (PCR) and direct sequencing methods were used to analyze the genotypes of CX3CL1, LEPR, and IL-6 polymorphisms. Multifactor dimensionality reduction (MDR) software was utilized to analyze gene-gene interactions. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used for evaluating the association between gene polymorphisms or gene-gene interactions and CAD risk. Results: In the study, TT genotype of rs170364 in CX3CL1 might decrease the CAD risk (OR=0.39, 95% CI=0.16-0.98). No significant correlation was found between T allele of rs170364 and CAD risk (P>0.05). CC genotype and C allele in rs614230 (CX3CL1) were significantly related with decreased risk of CAD (OR=0.38, 95% CI=0.17-0.86; OR=0.66, 95% CI=0.45-0.97). For IL-6 rs2066992 polymorphism. GG genotype could increase the risk of CAD (OR=2.32, 95% CI=1.04-5.17). Whereas, no significant correlation was observed between LEPR rs6700896 and CAD susceptibility. MDR analysis showed that CX3CL1, LEPR and IL-6 genes might jointly promote the occurrence of CAD. Conclusions: The interactions of CX3CL1, LEPR and IL-6 genes might increase the risk of CAD.     

Association of variants in CELSR2-PSRC1-SORT1 with risk of serum lipid traits,coronary artery disease and ischemic stroke

Recent genome-wide association studies (GWAS) have identified genetic variants associated with coronary artery disease (CAD), ischemic stroke (IS) and serum lipid traits in different ethnic groups. Some loci were found to affect the risk of CAD and IS. However, there were no data in the southern Chinese populations. Our study was to assess the association of CELSR2-PSRC1-SORT1 rs599839, rs464218 and rs6698443 SNPs and serum lipid levels and the risk of CAD and IS. The genotypes of 3 SNPs were detected in 561 CAD and 527 IS patients, and in 590 healthy controls. The genotypic and allelic frequencies of the rs599839 SNP were different between the controls and IS patients (P < 0.05). The minor G alleles of rs599839 and rs464218 SNPs were associated with higher high-density lipoprotein cholesterol concentrations in CAD and IS patients (P < 0.05); respectively. No association was found between the SNPs of rs599839, rs464218 and rs6698843 at the CELSR2-PSRC1-SORT1 and the risk of CAD or IS. These results will be replicated in the other Chinese populations.     

Interleukin-1β (3953/4) C→T polymorphism increases the risk of chronic periodontitis in Asians: evidence from a meta-analysis of 20 case-control studies

Introduction

To investigate the association of the interleukin-1β (IL-1β) (3953/4) C→T polymorphism with chronic periodontitis (CP) in Asians.

Material and methods

Systematic searches of electronic databases and hand searching of references were performed, including PubMed, Embase, the Cochrane Library, and the Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. Publication bias was tested by Egger''s test. Sensitivity analysis was conducted by limiting the meta-analysis studies conforming to Hardy-Weinberg equilibrium (HWE). Data analyses were carried out using RevMan 6.0.

Results

A meta-analysis was performed on 20 published case-control studies, including 1,656 CP cases and 1,498 healthy controls. The pooled OR was 1.60 (95% CI = 1.02–2.52, p = 0.04) for the T allele carriers (TT + CT) compared with CC and 1.60 (95% CI = 1.06–2.42, p = 0.02) for T vs. C. Subgroup analysis by country revealed significant risks of CP among Indians carrying the T allele (TT vs. CC: OR = 3.88, 95% CI = 1.77–8.50, p = 0.0007).

Conclusions

The analysis showed that IL-1β (3953/4) C→T polymorphism probably increases the risk of CP in Asians, and the IL-1β+3954 TT genotype may be associated with a strongly increased risk of CP in Indians, but not in Chinese.     

Matrix metalloproteinase 13 genotype in rs640198 polymorphism is associated with severe coronary artery disease

Atherosclerosis as a main etiopathogenetic source for coronary artery disease (CAD) development is intimately related to dynamic changes in the extracellular matrix (ECM). Elevated levels of MMP-13 have been observed in human atherosclerotic plaques which could also involve variability in MMP-13 gene. The aim of the study was to associate rs640198 polymorphism with CAD and/or with its severity.The study comprised 1071 consecutive patients with suspected or known coronary artery disease (CAD), confirmed by coronary angiography.Genotyping for the rs640198 polymorphism in MMP-13 gene was performed using Taqman® assay. The TT and TG genotypes of rs640198 polymorphism in MMP-13 gene confer the significantly increased risk of triple vessel disease compared to patients without atherosclerotic lesions in coronary arteries (odds ratio = 1.64, Pcorr = 0.05). Furthermore, an increased risk of having 5 and more stenoses (odds ratio = 1.90, Pcorr = 0.004) was observed in TT and TG carriers (sensitivity of 0.613 and a specificity of 0.544; power of the test is 0.87).The T allele of MMP-13 intron polymorphism rs640198 is associated with the severity of coronary artery disease, represented by the number of affected arteries as well as by the number of stenoses confirmed by coronarography.     

Association of two polymorphisms rs2910164 in miRNA-146a and rs3746444 in miRNA-499 with rheumatoid arthritis: A meta-analysis

Background

It has been reported that two single nucleotide polymorphisms (SNPs) rs2910164 in miRNA-146a and rs3746444 in miRNA-499 might be associated with the susceptibility to rheumatoid arthritis (RA). Owing to mixed and inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between the two SNPs and RA risk.

Methodology/main results

A systematic search of studies on the association of two SNPs with susceptibility to RA was conducted in PubMed and Embase. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. A total of 6 case-control studies on rs2910164 and 3 studies on rs3746444 were included. Though no evidence of association was found between rs2910164 polymorphism and RA risk in all the genetic models, a trend of reduced risk could be drawn. (C versus G: OR = 0.93, 95% CI 0.82–1.05; GC versus GG: OR = 0.89, 95% CI 0.73–1.10; CC versus GG: OR = 0.84, 95% CI 0.64–1.10; GC/CC versus GG: OR = 0.89, 95% CI 0.73–1.08; CC versus GC/GG: OR = 0.94, 95% CI 0.77–1.14). A significant increased risk of RA was observed in the rs3746444 polymorphism in homozygote comparison, recessive comparison, and allele comparison, but there was insufficient data to fully confirm the association of RA and rs3746444 in miRNA-499.

Conclusions

MiRNA-146a rs2910164 polymorphism is not associated with RA risk, while miRNA-499 rs3746444 polymorphism is correlated with RA risk. However, the results of miRNA-499 rs3746444 should be interpreted with caution due to limited sample and heterogeneity. Large-scale and well-designed studies are needed to validate our findings.     

Apolipoprotein E and α-1-antichymotrypsin allele polymorphism in sporadic and familial Alzheimer's disease

Alzheimer disease (AD) patients with both sporadic and familial forms of AD and non-demented controls were genotyped for common polymorphisms in the signal peptide for α-1-antichymotrypsin (ACT) gene and in two different regions of apolipoprotein E (APOE) gene. The ACT TT genotype was over-represented (P=0.025) in patients with early onset of sporadic AD. In this patient's group ACT TT genotype conferred a significant crude odds ratio for the disease (OR=2.09; 95% CI=1.09–4.00, P=0.025). After adjustment for the APOE ε4 and APOE −491 genotypes, logistic regression analysis confirmed that the ACT TT genotype resulted independently associated with early onset AD (adjusted OR=2.56; 85% C.I.=1.3–5.2, P=0.009). The frequency of APOE ε4 allele was increased in AD, as expected (OR=5.92, 95% CI=3.60–9.70, P=0.0001). On the contrary, the APOE −491 A/T genotypes were not associated with AD. No preferential association of the APOE ε4 allele or APOE −491 A/T genotypes with ACT A/T alleles was observed in AD. Present findings indicated that subjects with ACT TT genotype had an increased risk of developing AD and suggested that this genotype influenced the risk of an early onset of the disease by affecting the production of ACT molecules.     

Interleukin-17A gene polymorphism is associated with susceptibility to gastric cancer

We conducted a study to investigate the role of three common SNPs in the IL-17A and IL-17F genes (rs2275913G>A, rs3748067C>T and rs763780T>C) in the development of gastric cancer, and their interaction with H.pylori infection. A total of 326 patients with gastric cancer and 326 control subjects were consecutively recruited between May 2012 and May 2014. Genotyping of IL-17A rs2275913G>A and rs3748067C>T and IL-17F rs763780T>C was performed in a 384-well plate format on the Sequenom MassARRAY platform. By logistic regression analysis, individuals carrying the GA and AA genotypes of IL-17 rs2275913G>A were significantly associated with an increased risk of gastric cancer when compared with GG genotype, and the adjusted Ors (95% CI) were 1.46 (1.03-2.06) for GA genotype and 2.57 (1.51-4.43) for AA genotype. We observed that the GA+AA genotype of rs2275913 was associated with an increased risk of gastric cancer among H.pylori infection subjects (OR=2.21, 95% CI=1.29-3.79). In conclusion, we found that there was a significant association between L-17A rs2275913G>A polymorphism and increased gastric cancer risk, especially in H.pylori infection subjects.     

Association between Interleukin-27 gene polymorphisms and susceptibility to allergic rhinitis

Objectives

Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Interleukin-27 (IL-27), a novel IL-12 family member, has recently been reported to play a role in some immune-related disorders. This study was performed to evaluate the potential association of IL-27 polymorphisms with AR in a Chinese Han population.

Design and Methods

A case-control study was performed in 445 Chinese AR patients and 691 healthy controls. Three SNPs in the IL-27p28 gene, including rs153109, rs17855750 and rs181206, were detected using a polymerase chain reaction–restriction fragment length polymorphism assay (PCR–RFLP).

Results

A significantly increased prevalence of the rs153109 TT genotype and the T allele was found in AR patients, while a decreased prevalence of the CT and CC genotypes and the C allele was found. For rs153109, the TT genotype and the T allele were significantly associated with the risk of AR, but the CT and CC genotypes and the C allele decreased the risk of AR; for rs17855750, the TT genotype and T allele were risk factors for AR, and the GT genotype and G allele provided protection. TTT and TTC haplotypes in the IL-27p28 gene were positively correlated with AR, while CGT, CTC and CTT haplotypes were associated with a significantly decreased risk of AR.

Conclusion

This study indicates that IL-27p28 polymorphisms rs153109 and rs17855750 are likely involved in AR susceptibility, making them potentially useful genetic biomarkers for AR susceptibility in the Chinese Han population.     

CD38 Gene polymorphisms and susceptibility to B cell chronic lymphocytic leukemia

CD38 was suggested to be not only a prognostic marker but also a key element in the pathogenetic network underlying chronic lymphocytic leukemia (CLL). We aimed at determining whether polymorphisms of CD38 gene influence the risk of B-CLL and thus analyzed two potentially functional CD38 single nucleotide polymorphisms (SNPs), rs6449182 (184 C>G), and rs1800561 (418 C>T) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based assays in a study including 70 B-CLL patients and 70 age- and gender-matched controls. Our results demonstrated that the homozygous mutant genotypes of the two studied SNPs (GG and TT) showed a significantly higher risk of B-CLL compared with the homozygous wild types (p value?<?0.001, OR?=?2.813, 95% CI?=?1.898–4.168 and p value?=?0.011, OR?=?2.250, 95%CI?=?1.707–2.96, respectively). In addition, G and T carriers had more advanced clinical stage (p value?<?0.001). Also, a significant association was demonstrated between higher proportions of CD38-positive cells and carriers of G and T alleles (p value?<?0.001). Our data suggest that the risk of B-CLL carcinogenesis may be influenced by CD38 SNPs [rs6449182 (184 C>G) and rs1800561 (418 C>T)].     

CD40 -1C>T polymorphism and the risk of lung cancer in a Chinese population

Background: The co-stimulatory molecule CD40 plays an important role in anti-tumor responses by promoting cytotoxic T lymphocyte (CTL) activity and differentiation of helper T cells. Growing evidence suggests that single nucleotide polymorphisms (SNPs) in CD40 are associated with the susceptibility to cancer. This study investigated the association between the CD40 -1C/T SNP (rs1883832) and lung cancer in a Chinese population. Methods: We conducted a hospital-based case-control study including 105 lung cancer patients and 109 healthy control subjects. The -1C/T SNP in CD40 was genotyped by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), and its association with lung cancer susceptibility was evaluated. Results: The distribution of the genotypes of CD40-1C/T was significantly different between lung cancer patients and controls. The frequency of the TT genotype (adjusted P = 0.017; overall risk [OR] = 2.94; 95% confidence interval [CI] = 1.21-7.13) and TT/CT genotype (adjusted P = 0.020; OR = 1.95; 95% CI = 1.11-3.43) were significantly higher in lung cancer patients than that in controls. When the cases were categorized by tumor histology, the TT genotype was associated with a significantly increased risk of squamous cell carcinoma (adjusted OR = 6.53; 95% CI = 1.97-21.61; P = 0.002). Conclusion: Our findings suggest that the CD40 -1C/T SNP (rs1883832) is correlated with the susceptibility to lung cancer in Chinese, and the TT genotype may further increase the risk of lung cancer.     

Thermolabile methylenetetrahydrofolate reductase C677T polymorphism and homocysteine are risk factors for coronary artery disease in Moroccan population

Increased plasma total homocysteine (tHcy) levels have been shown to be a risk factor for coronary artery disease (CAD). The common methylenetetrahydrofolate reductase C677T (MTHFR C677T) polymorphism has been reported to be a strong predictor of mild hyperhomocysteinaemia (HHcy). We assessed whether this mutation was associated with increased risk of CAD and plasma levels of tHcy. We also evaluated interactions between this polymorphism, mild elevated tHcy levels and conventional risk factors of CAD. Method. Using PCR-RFLP analysis, we studied the frequency of the C677T genotypes and its effect on CAD and on tHcy concentrations in 400 subjects without and with CAD angiographically confirmed. There were 210 subjects with CAD and 190 subjects without CAD. Results. The frequencies of the C677T genotypes were 53% (59.5% in controls versus 48.1% in cases), 34.8% (32.1 in controls versus 37.1 in cases), and 11.8% (8.4% in controls versus 14.8% in cases), respectively, for 677CC, 677CT, and 677TT. The genotype frequencies were significantly different between case and control groups (P < .05). The 677T allele enhances the risk of CAD associated to HHcy (P < .01). In multivariate analysis models, MTHFR C677T polymorphism effect on CAD was masked by other risk factors. HHcy was only and independently influenced by MTHFR polymorphism and smoking habits, and it is a strong predictor of CAD independently of conventional risk factors. Conclusion. Our data suggest that HHcy is strongly and independently associated to CAD risk increase; and MTHFR C677T polymorphism and smoking habits were the main predictors of tHcy levels. The CAD risk increase is mainly associated with mild HHcy in 677TT, whereas in 677CT and 677CC it is mainly associated with the conventional risk factors.