Polymorphisms in <Emphasis Type="Italic">VEGF-A</Emphasis> are associated with COPD risk in the Chinese population from Hainan province

In this study, we examined and validated how common variants contribute to susceptibility to chronic obstructive pulmonary disease (COPD) in the Han Chinese population. Here, we genotyped 18 nucleotide polymorphisms and evaluated their association with COPD using chi-square test and genetic model analysis (246 COPD patients and 350 controls), and found three SNPs that might cause a predisposition to COPD. Both rs3025030 and rs3025033 are located on chromosome 6 in VEGF-A. We found one risk allele ‘C’ from rs3025030 and another ‘G’ from rs3025033 using the log-additive model (OR 1.40; 95% CI 1.05–5.96; P = 0.022), (OR 1.38; 95% CI 1.03–1.84; P = 0.03). We also found another risk allele ‘A’ of rs9296092 in gene region ZBTB9-BAK1 by the allele model (OR 2.63; 95% CI 1.27–5.45; P = 0.0078), (adjusted OR 3.53; 95% CI 1.12–11.11; P = 0.031). We found a risk haplotype ‘CG’ associated with the risk of COPD (OR 1.39; 95% CI 1.04–1.86; P=0.028). Our results when compared with previous studies showed significant association between VEGF-A polymorphism and COPD. We also identified rs9296092 as a risk factor for COPD.     

Fibroblast growth factor receptor 4 polymorphisms and coronary artery disease: a case control study

Fibroblast growth factors (FGFs) and their receptors (FGFRs) play important roles in vascular system. FGFR4 rs351855 (Gly388Arg) polymorphism has shown to be a risk factor for many diseases. The aim of this study was to investigate the association between FGFR4 polymorphisms and the susceptibility to coronary artery disease (CAD) in the Chinese population. We identified three polymorphisms in the FGFR4 gene, rs351855G/A (Gly388Arg), rs145302848C/G and rs147603016G/A, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 658 CAD cases and 692 healthy controls. Results showed that frequencies of GA genotype, AA genotype and A allele in rs351855 (Gly388Arg) polymorphism were significantly lower in CAD patients than in controls [odds ratio (OR) = 0.79, 95 % confidence intervals (CI) 0.62-0.99, P = 0.042; OR = 0.58, 95 % CI 0.41-0.81, P = 0.002; and OR = 0.77, 95 % CI 0.66-0.90, P = 0.001, respectively]. The rs147603016GA genotype and A allele also showed lower numbers in CAD cases (OR = 0.58, 95 % CI 0.36-0.93, P = 0.025; and OR = 0.59, 95 % CI 0.40-0.95, P = 0.028). The rs145302848C/G polymorphism did not show any correlation with CAD. Haplotype analysis revealed that the prevalence of ACG haplotype (rs351855, rs145302848 and rs147603016) was significantly decreased in CAD patients (P = 0.002). Our data suggested that the FGFR4 rs351855G/A (Gly388Arg) and rs147603016G/A polymorphisms could act as protective factors against CAD in the Chinese population and indicated that a single gene polymorphism could have diverse functions in different diseases.     

Association of interleukin (IL)-12 and IL-27 gene polymorphisms with chronic obstructive pulmonary disease in a Chinese population

The pathogenesis of chronic obstructive pulmonary disease (COPD) is not fully understood, and environment and genetic factors have been investigated. Moreover, cytokine genes play an important role in COPD pathogenesis. However, the molecular mechanism of COPD induced by the factors is still unknown. The present study was undertaken to clarify a role of interleukin (IL)-12 16974A/C and IL-27 4730T/C, -964A/G, and 2905T/G polymorphisms in Chinese subjects with COPD. Polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) and sequence analyses were used to type IL-12 and IL-27 polymorphisms in 120 patients with COPD and 100 healthy controls. There were significant differences in the genotype and allele distribution of -964A/G and 2905T/G polymorphisms of the IL-27 gene among cases and controls in a Chinese population. When compared with the control group, subjects with AG genotype of the IL-27 -964A/G had a 2.22-fold decreased risk of COPD (odds ratio [OR] = 0.450, 95% confidence interval [CI]: 0.245-0.826; p = 0.009), and subjects with TG genotype of the IL-27 2905T/G had a 2.85-fold decreased risk of COPD (OR = 0.351, 95% CI: 0.137-0.899; p = 0.024). Compared with the TAT haplotype, the TGG haplotype was associated with a significantly decreased risk of COPD (OR = 0.29, 95% CI: 0.108-0.784; p = 0.010). Even after Bonferroni corrections, significant associations with COPD were observed for the AG genotype of the IL-27 -964A/G and the TGG haplotype of the IL-27 gene. Our data suggest that polymorphisms in the IL-27 gene may play a role in the development of COPD in Chinese population.     

ECE1 polymorphisms may contribute to the susceptibility of sporadic congenital heart disease in a Chinese population

Endothelin-converting enzyme-1 (ECE1) plays a key role in the development of a subset of neural crest lineages such as cardiogenesis. Genetic variants of ECE1 C338A (rs213045) and T839G (rs213046) have been shown to alter ECE1 expression. This observation led us to hypothesize that two polymorphisms might influence the susceptibility of sporadic congenital heart disease (CHD). We conducted a case-control study comprised of 945 CHD cases and 972 non-CHD controls in a Chinese population. We tested our hypothesis by genotyping ECE1 C338A and T839G and assessed their association with the risk of CHD. Compared with the 338 CC and the 839 TT genotypes, the ECE1 338 AA/AC and 839 TG/GG genotypes significantly increased the risk of CHD (adjusted odds ratio [OR]=1.38, 95% confidence interval [CI]=1.14-1.68; and adjusted OR=1.30, 95% CI=1.07-1.58, respectively). A combined analysis was performed that showed that the presence of 2-4 risk alleles (the ECE1 338A and 839G allele) increased the risk of CHD by 2.07-fold compared with 0-1 risk alleles. Furthermore, we found that the association between 2-4 risk alleles and CHD risk was stronger in females (adjusted OR=1.77, 95% CI=1.31-2.40) than males (adjusted OR=1.33, 95% CI=1.03-1.71), and in the phenotypes of Tetralogy of Fallot (adjusted OR=1.84, 95% CI=1.10-3.06) and perimembranous ventricular septal defect (pmVSD) (adjusted OR=1.74, 95% CI=1.35-2.24). Our results suggest that ECE1 polymorphisms may contribute to the susceptibility of sporadic CHD in a Chinese population.     

SLC6A4基因多态性与海洛因依赖的关联性研究

目的:探讨5-羟色胺转运体基因(solute carrier family 6 member 4,SLC6A4)基因4个单核苷酸多态性(single nucleotide polymorphism,SNP)位点与海洛因依赖之间的关系。方法:严格按照诊断标准,选取无亲缘关系的海洛因依赖个体397例(病例组)及健康对照个体402例(对照组)提取基因组DNA,采用SNaPshot SNP分型技术对SLC6A4基因4个SNP位点(rs1042173,rs3813034,rs6354,rs7224199)进行基因分型,比较病例-对照组间各位点等位基因、基因型频率的差异。结果:病例组和对照组SLC6A4基因rs1042173和rs3813034位点的基因型和等位基因频率比较存在显著性差异(P0.05),rs1042173的C等位基因(P=0.031,OR=1.317,95%CI=1.026-1.691)及rs3813034的C等位基因(P=0.013,OR=1.375,95%CI=1.069-1.768)是海洛因依赖的危险因素。病例组TCC单倍型(rs7224199、rs3813034和rs1042173)的比例较对照组显著增高(P0.05)。结论:SLC6A4基因rs1042173和rs3813034多态性可能与海洛因成瘾有关,携带有rs1042173的C等位基因和rs3813034的C等位基因的个体及携带TCC单倍型的个体可能更容易对海洛因产生依赖。     

Investigation of IGF1, IGF2BP2, and IGFBP3 variants with lymph node status and esophagogastric junction adenocarcinoma risk

Esophagogastric junction adenocarcinoma (EGJA) may be associated with obesity and overweight. Thus, any variant in energy metabolism–related gene may influence the development of EGJA. In this study, we recruited 720 EGJA cases and 1541 noncancer controls. We selected IGF2BP2 rs4402960 G > T, rs1470579 A > C, IGF1 rs5742612 A > G and IGFBP3 rs3110697 G > A, rs2270628 C > T and rs6953668 G > A loci and assessed the relationship of these polymorphisms with lymph node status and susceptibility of EGJA. We found that IGF2BP2 rs1470579 A > C and IGFBP3 rs6953668 G > A polymorphisms were associated with the decreased risk of EGJA ( IGF2BP2 rs1470579: CC vs AA: adjusted odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.43-0.98, P = 0.041 and CC vs AA/AC: adjusted OR = 0.62, 95% CI = 0.41-0.93, P = 0.021 and IGFBP3 rs6953668: GA vs GG: adjusted OR = 0.66, 95% CI = 0.47-0.93, P = 0.019 and GA/AA vs GG: adjusted OR = 0.68, 95% CI = 0.48-0.95, P = 0.026). However, we also found that IGF1 rs5742612 A > G polymorphism increased the risk of LNM among patients with EGJA (GG vs AA: adjusted OR = 1.88, 95% CI = 1.02-3.46, P = 0.042 and GG vs AA/AG: adjusted OR = 1.92, 95% CI = 1.06-3.47, P = 0.032). This study suggests that IGF2BP2 rs1470579 A > C and IGFBP3 rs6953668 G > A polymorphisms may decrease genetic susceptibility to EGJA in eastern Chinese Han population. In addition, our findings also indicate that IGF1 rs5742612 A > G polymorphism may increase the susceptibility of LNM among patients with EGJA.     

SLC11A1 (NRAMP1) polymorphisms and tuberculosis susceptibility: updated systematic review and meta-analysis

Background

Natural resistance associated macrophage protein 1 (NRAMP1), encoded by the SLC11A1 gene, has been described to regulate macrophage activation and be associated with infectious and autoimmune diseases. The relation between SLC11A1 polymorphisms and tuberculosis susceptibility has been studied in different populations.

Methods

We systematically reviewed published studies on SLC11A1 polymorphisms and tuberculosis susceptibility until September 15, 2010 and quantitatively summarized associations of the most widely studied polymorphisms using meta-analysis.

Results

In total, 36 eligible articles were included in this review. In Meta-analysis, significant associations were observed between tuberculosis risk and widely studied SLC11A1 polymorphisms with summarized odds ratio of 1.35 (95%CI, 1.17–1.54), 1.25 (95% CI, 1.04–1.50), 1.23 (95% CI, 1.04–1.44), 1.31 (95%CI, 1.08–1.59) for 3′ UTR, D543N, INT4, and 5′ (GT)n, respectively. Heterogeneity between studies was not pronounced, and the associations did not remarkably vary in the stratified analysis with respect to study population and study base.

Conclusions

The association between SLC11A1 polymorphisms and tuberculosis susceptibility observed in our analyses supports the hypothesis that NRAMP1 might play an important role in the host defense to the development of tuberculosis.     

C-X-C chemokine receptor type 5 gene polymorphisms are associated with non-Hodgkin lymphoma

The C-X-C chemokine receptor type 5 (CXCR5) is one of the principal regulators for targeting T cells, B cells and dendritic cells into secondary lymphoid organs. Polymorphism studies of CXCR5 gene remain extremely scarce. The aim of this study was to examine the effect of polymorphisms in the CXCR5 gene on the development of non-Hodgkin lymphoma (NHL) in the Chinese population. Four polymorphisms in CXCR5 gene, rs148351692C/G, rs6421571C/T, rs80202369G/A and rs78440425G/A, were tested by polymerase chain reaction-restriction fragment length polymorphism in 404 NHL cases and 456 age-matched healthy controls. Data were analyzed using the χ(2) test. Results showed that individuals with the rs6421571 CT, rs6421571 TT and rs80202369 AA genotype had significantly increased susceptibility to NHL [Odd ratio (OR) = 1.41, 95 % confidence interval (CI): 1.04-1.92, p = 0.028; OR = 2.30, 95 % CI: 1.44-3.65, p < 0.001; and OR = 3.24, 95 % CI: 1.26-8.32, p = 0.010, respectively]. When analyzing the haplotypes of these polymorphisms, the prevalence of the TGG (rs6421571, rs80202369, and rs78440425) haplotype was significantly higher in NHL cases than in controls (OR = 1.59, 95 % CI: 1.25-2.03, p < 0.001). In addition, numbers of rs6421571 TT genotype and T allele were significantly increased in NHL patients with high Ann Arbor stages (p < 0.03) or NHL with B cell subtype (p < 0.02). These data indicate that CXCR5 gene polymorphisms may be new risk factors for NHL. The finding that the adjacent SNPs, rs6421571C/T and rs80202369G/A, are both associated with NHL suggests that the 87 bp region carrying these 2 polymorphisms may have important functional significance.     

Associations of Genetic Variants in the PSCA,MUC1 and PLCE1 Genes with Stomach Cancer Susceptibility in a Chinese Population

BackgroundSeveral genetic variants including PSCA rs2294008 C>T and rs2976392 G>A, MUC1 rs4072037 T>C, and PLCE1 rs2274223 A>G have shown significant association with stomach cancer risk in the previous genome-wide association studies (GWASs).MethodsTo evaluate associations of these SNPs in the Han Chinese, an independent hospital based case-control study was performed by genotyping these four polymorphisms in a total of 692 stomach cancer cases and 774 healthy controls acquired by using frequency matching for age and gender. False-positive report probability (FPRP) analysis was also performed to validate all statistically significant findings.ResultsIn the current study, significant association with stomach cancer susceptibility was observed for all the four polymorphisms of interest. Specifically, a significant increased stomach cancer risk was associated with PSCA rs2294008 (CT vs. CC: adjusted OR = 1.37, 95% CI = 1.07–1.74, and CT/TT vs.CC: adjusted OR = 1.30, 95% CI = 1.03–1.63), PSCA rs2976392 (AG vs. GG: adjusted OR = 1.30, 95% CI = 1.02–1.65, and AG/AA vs. GG: adjusted OR = 1.26, 95% CI = 1.00–1.59), or PLCE1 rs2274223 (AG vs. AA: adjusted OR = 1.48, 95% CI = 1.15–1.90, and AG/GG vs. AA: adjusted OR = 1.45, 95% CI = 1.14–1.84), respectively. In contrast, MUC1 rs4072037 was shown to decrease the cancer risk (CT vs. TT: adjusted OR = 0.77, 95% CI = 0.60–0.98). Patients with more than one risk genotypes had significant increased risk to develop stomach cancer (adjusted OR = 1.30, 95% CI = 1.03–1.64), when compared with those having 0–1 risk genotypes. Stratified analysis indicated that the increased risk was more pronounced in younger subjects, men, ever smokers, smokers with pack years ≤ 27, patients with high BMI, or non-cardia stomach cancer.ConclusionsThis study substantiated the associations between four previous reported genetic variants and stomach cancer susceptibility in an independent Han Chinese population. Further studies with larger sample size and different ethnicities are warranted to validate our findings.     

Two genetic variants in FABP1 and susceptibility to non-alcohol fatty liver disease in a Chinese population

Liver fatty acid-binding protein (FABP1) serves as a key regulator of hepatic lipid metabolism, and polymorphisms within the FABP1 gene have been associated with several metabolic traits. To investigate the association between FABP1 polymorphisms and the risk of non-alcohol fatty liver disease (NAFLD) in a Chinese population, the genotypes and haplotypes of FABP1 (rs2241883 T/C and rs1545224G/A) were determined in 553 patients with NAFLD and 553 healthy controls. The results showed that individuals with at least one copy of the rs2241883 C allele (TC or CC genotype) had an elevated risk for developing NAFLD (odds ratio [OR]=1.32, 95% CI: 1.01-1.71), and individuals with at least one copy of the rs1545224 A allele (GA or AA genotype) also had a significantly increased risk for NAFLD (OR=1.52, 95% CI: 1.14-2.02). Cumulative effect analysis of the two SNPs revealed that individuals with two risk genotypes were at significantly higher risk of NAFLD than those without risk genotype, and a significant trend of increased risk with increasing numbers of risk genotype was observed. Stratification analysis showed that the rs2241883 C allele carriers had higher level of LDL-C and the rs1545224 A allele carriers had higher level of FPG than those without this allele. In addition, haplotype analysis revealed that the one composed of the rs1545224 A and rs2241883 C variants was significantly associated with an increased risk for NAFLD (OR=1.34; 95% CI=1.05-1.40) compared to the GT haplotype. Taken together, the present study suggests that genetic variations within FABP1 influence susceptibility to NAFLD independently or jointly.     

Association of excision repair cross-complimentary group 1 gene polymorphisms with breast and ovarian cancer susceptibility

The role of excision repair cross-complimentary group 1 (ERCC1) gene polymorphisms in breast and ovarian cancer development has long been controversial and existing data were inconsistent. Here, we conducted a comprehensive meta-analysis to better clarify the association. Case-control studies published from December 2008 to November 2018 were assessed. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated. Fifteen articles with 24 case-control studies and 3 ERCC1 polymorphisms were enrolled. A total of 20 923 participants including 9896 cases and 11 027 controls were analyzed. The results showed that C to T variation in the ERCC1 rs11615 (C/T) polymorphisms was correlated with breast cancer susceptibility (T vs C: OR = 1.19, 95% CI = 1.02-1.38; TT + CT vs CC: OR = 1.24, 95% CI = 1.12-1.36). ERCC1 rs3212986 (C/A) polymorphisms posed an increased risk for breast and ovarian cancer as whole (A vs C: OR = 1.12, 95% CI = 1.01-1.25; AA + CA vs CC: OR = 1.11, 95% CI = 1.02-1.22), and presented especially higher risk for ovarian cancer (A vs C: OR = 1.31, 95% CI = 1.05-1.63; AA vs CA + CC: OR = 1.66, 95% CI = 1.12-2.47; AA vs CC: OR = 1.72, 95% CI = 1.12-2.64). Meanwhile, neither overall group analyses nor stratified analyses displayed any association of ERCC1 rs2298881 (A/C) polymorphisms in breast and ovarian cancer susceptibility. This meta-analysis suggested that ERCC1 rs11615 (C/T) polymorphisms were associated with breast cancer susceptibility and rs3212986 (C/A) polymorphisms were especially correlated with ovarian cancer risk. More case-control studies with well-adjusted data and diverse populations are essential for validation of our conclusion.     

Association of TNF-alpha/LTA polymorphisms with Crohn's disease in Koreans

Polymorphisms of the proinflammatory and immunoregulatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin-alpha (LTA), have been shown to affect their production and be associated with Crohn's disease. However, the actual alleles associated with the disease are variable among populations. The aim of this study was to test whether TNF-alpha and LTA polymorphisms were associated with Crohn's disease risk in Korean samples. Genotyping for five TNF-alpha promoter polymorphisms (-1031, -863, -857, -308, and -238) and two LTA polymorphisms (intron 1 and Thr60Asn) were performed on 289 Korean patients with Crohn's disease and 399 unrelated healthy controls. Carriers of an individual polymorphism of TNF-alpha at -857T, showed statistically significant association with Crohn's disease (adjusted OR=1.64, 95% CI=1.11-2.41, P=0.013). Following haplotype analysis, carriers of the haplotype consisted of the -1031C, -863A, and -857C alleles showed statistically significant association with Crohn's disease (adjusted OR=1.54, 95% CI=1.02-2.32, P=0.040). Significantly reduced frequencies were seen for the carriers of the LTA Thr60Asn polymorphism in patients (OR=0.62; 95% CI=0.42-0.93, P=0.019), suggesting a protective effect on Crohn's disease. Our data support the hypothesis that the TNF-alpha/LTA genotypes play an important role in the pathogenesis of Crohn's disease in Koreans.     

Osteopontin and systemic lupus erythematosus association: a probable gene-gender interaction

Osteopontin (SPP1) is an important bone matrix mediator found to have key roles in inflammation and immunity. SPP1 genetic polymorphisms and increased osteopontin protein levels have been reported to be associated with SLE in small patient collections. The present study evaluates association between SPP1 polymorphisms and SLE in a large cohort of 1141 unrelated SLE patients [707 European-American (EA) and 434 African-American (AA)], and 2009 unrelated controls (1309 EA and 700 AA). Population-based case-control association analyses were performed. To control for potential population stratification, admixture adjusted logistic regression, genomic control (GC), structured association (STRAT), and principal components analysis (PCA) were applied. Combined analysis of 2 ethnic groups, showed the minor allele of 2 SNPs (rs1126616T and rs9138C) significantly associated with higher risk of SLE in males (P = 0.0005, OR = 1.73, 95% CI = 1.28-2.33), but not in females. Indeed, significant gene-gender interactions in the 2 SNPs, rs1126772 and rs9138, were detected (P = 0.001 and P = 0.0006, respectively). Further, haplotype analysis identified rs1126616T-rs1126772A-rs9138C which demonstrated significant association with SLE in general (P = 0.02, OR = 1.30, 95%CI 1.08-1.57), especially in males (P = 0.0003, OR = 2.42, 95%CI 1.51-3.89). Subgroup analysis with single SNPs and haplotypes also identified a similar pattern of gender-specific association in AA and EA. GC, STRAT, and PCA results within each group showed consistent associations. Our data suggest SPP1 is associated with SLE, and this association is especially stronger in males. To our knowledge, this report serves as the first association of a specific autosomal gene with human male lupus.     

Genetic variation in the NBS1 gene is associated with hepatic cancer risk in a Chinese population

NBS1 plays important roles in maintaining genomic stability as a key DNA repair protein in the homologous recombination repair pathway and as a signal modifier in the intra-S phase checkpoint. We hypothesized that polymorphisms of NBS1 are associated with hepatic cancer (HCC) risk. The NBS1 rs1805794 C/G polymorphism has been frequently studied in some cancers with discordant results, but its association with HCC has not been investigated. Moreover, studies of the 3'UTR variant rs2735383 have not touched upon HCC. This study examined the contribution of these two polymorphisms to the risk of developing HCC in a Chinese population. NBS1 genotypes were determined in 865 HCC patients and 900 controls and the associations with risk of HCC were estimated by logistic regression. Compared with the rs1805794 GG genotype, the GC genotype had a significantly increased risk of HCC (adjusted odds ratios [OR]=1.41; 95% confidence interval [CI]=1.11-1.80), the CC carriers had a further increased risk of HCC (OR=2.27; 95% CI=1.68-3.14), and there was a trend for an allele dose effect on risk of HCC (p<0.001). Also, we found that the risk effect of rs1805794 CC+CG was more pronounced in HCC patients that drank (OR=2.28, 95% CI=1.55-3.29 for drinkers; OR=1.31, 95% CI=1.00-1.77 for nondrinkers). However, there was no significant difference in genotype frequencies of rs2735383 G/C site between cases and controls. These findings suggest that rs1805794 C/G polymorphism in NBS1 may be a genetic modifier for developing HCC.     

Association of RET Genetic Polymorphisms and Haplotypes with Papillary Thyroid Carcinoma in the Portuguese Population: A Case-Control Study

Thyroid cancer has a multifactorial aetiology resulting from the interaction of genetic and environmental factors. Several low penetrance susceptibility genes have been identified but their effects often vary between different populations. Somatic point mutations and translocations of the REarranged during Transfection (RET) proto-oncogene are frequently found in thyroid cancer. The aim of this case-control study was to determine the effect of four well known RET single nucleotide polymorphisms (SNPs) on the risk for differentiated thyroid carcinoma. A total of 545 Portuguese patients and 543 controls were genotyped by PCR and restriction enzyme analysis, for the following SNPs: G691S (exon 11, rs1799939 G/A), L769L (exon 13, rs1800861 T/G), S836S (exon 14, rs1800862 C/T), and S904S (exon 15, rs1800863 C/G). The minor allele of S836S was overrepresented in patients with papillary thyroid carcinoma (PTC) when compared to controls (OR 1.57; 95% CI 1.05–2.35; p = 0.026). The GGTC haplotype was also overrepresented in PTC (OR 2.51; 95% CI 1.07–5.91; p = 0.029). No associations were found in follicular thyroid carcinoma (FTC). Multivariate logistic regression analysis showed no differences regarding gender, age at diagnosis, lymph node or distant metastasis. However, a near significant overrepresentation of the minor alleles of G691S and S904S was found in patients with tumours greater than 10 mm of diameter at diagnosis. These data suggest that the RET S836S polymorphism in exon 14 and the GGTC haplotype are risk factors for PTC, but not FTC, and that the G691S/S904S polymorphisms might be associated with tumour behaviour.     

Association of leishmaniasis with TNF alpha promoter and SLC11A1 gene polymorphisms in patients of two endemic areas in Mexico

Some Single Nucleotide Polymorphisms (SNPs) of interleukins and other modulatory molecules of the immune response play an important role in susceptibility to infectious diseases, particularly those involving intracellular parasites. In this study, we evaluated allele, genotype and haplotype associations of two SNPs of the TNF-α promoter and seven of the SLC11A1 gene in 79 patients with localized cutaneous leishmaniasis (CL) and 15 with visceral leishmaniasis (VL), compared with 127 and 89 locality paired controls, respectively, from two endemic areas of Chiapas State, Mexico. None of the TNF-α alleles and genotypes was associated either to CL or to VL. Alleles rs2276631-C (P = 0.02; OR [95%CI] = 2.11 [1.16–3.86]) and rs2279015-G (P = 0.005; OR [95%CI] = 2.42 [1.33–4.41]) of SLC11A1, were associated with susceptibility to VL, whereas genotypes rs2276631 C/C (P = 0.003; OR [95%CI] = 2.65 [1.41–5.00]) and rs2279015 G/G (P = 0.018; OR [95%CI] = 2.05 [1.15–3.64]) were significantly increased in CL and VL patients, respectively. Complete haplotypes involved in susceptibility were CGCCGDins with VL and CGCCADins with CL. CGCCA was the minimal susceptibility haplotype for CL and CCG for VL. Our data suggest that SLC11A1 gene polymorphisms might have a relevant role in the pathology of leishmaniasis, directing towards susceptibility outcome of this disease in residents of an endemic area.     

Polymorphisms in the AKT1 and AKT2 genes and oesophageal squamous cell carcinoma risk in an Eastern Chinese population

Ethnic Han Chinese are at high risk of developing oesophageal squamous cell carcinoma (ESCC). Aberrant activation of the AKT signalling pathway is involved in many cancers, including ESCC. Some single nucleotide polymorphisms (SNPs) in genes involved in this pathway may contribute to ESCC susceptibility. We selected five potentially functional SNPs in AKT1 (rs2494750, rs2494752 and rs10138277) and AKT2 (rs7254617 and rs2304186) genes and investigated their associations with ESCC risk in 1117 ESCC cases and 1096 controls in an Eastern Chinese population. None of individual SNPs exhibited an association with ESCC risk. However, the combined analysis of three AKT1 SNPs suggested that individuals carrying one of AKT1 variant genotypes had a decreased ESCC risk [adjusted odds ratio (OR) = 0.60, 95% CI = 0.42–0.87]. Further stratified analysis found that AKT1 rs2294750 SNP was associated with significantly decreased ESCC risk among women (adjusted OR = 0.63, 95% CI = 0.43–0.94) and non‐drinkers (OR = 0.79, 95% CI = 0.64–0.99). Similar protective effects on women (adjusted OR = 0.56, 95% CI = 0.37–0.83) and non‐drinker (adjusted OR = 0.75, 95% CI = 0.60–0.94) were also observed for the combined genotypes of AKT1 SNPs. Consistently, logistic regression analysis indicated significant gene–gene interactions among three AKT1 SNPs (P < 0.015). A three‐AKT1 SNP haplotype (C‐A‐C) showed a significant association with a decreased ESCC risk (adjusted OR = 0.70, 95% CI = 0.52–0.94). Multifactor dimensionality reduction analysis confirmed a high‐order gene–environment interaction in ESCC risk. Overall, we found that three AKT1 SNPs might confer protection against ESCC risk; nevertheless, these effects may be dependent on other risk factors. Our results provided evidence of important gene–environment interplay in ESCC carcinogenesis.     

Genetic Variants of Angiotensin-Converting Enzyme Are Linked to Autism: A Case-Control Study

BackgroundAutism is a disease of complex nature with a significant genetic component. The importance of renin-angiotensin system (RAS) elements in cognition and behavior besides the interaction of angiotensin II (Ang II), the main product of angiotensin-converting enzyme (ACE), with neurotransmitters in CNS, especially dopamine, proposes the involvement of RAS in autism. Since the genetic architecture of autism has remained elusive, here we postulated that genetic variations in RAS are associated with autism.MethodsConsidering the relation between the three polymorphisms of ACE (I/D, rs4343 and rs4291) with the level of ACE activity, we have investigated this association with autism, in a case-control study. Genotype and allele frequencies of polymorphisms were determined in DNAs extracted from venous blood of 120 autistic patients and their age and sex-matched healthy controls, using polymerase chain reaction (PCR) and PCR–restriction fragment length polymorphism (PCR–RFLP) methods.ResultsThere were strong associations between both DD genotype of ACE I/D and the D allele, with autism (P = 0.006, OR = 2.9, 95% CI = 1.64–5.13 and P = 0.006, OR = 2.18, 95% CI = 1.37–3.48 respectively). Furthermore, a significant association between the G allele of rs4343 and autism was observed (P = 0.006, OR = 1.84, 95%CI = 1.26–2.67). Moreover, haplotype analysis revealed an association between DTG haplotype and autism (P = 0.008).ConclusionOur data suggests the involvement of RAS genetic diversity in increasing the risk of autism.     

Cytotoxic T-lymphocyte antigen-4 polymorphisms and susceptibility to osteosarcoma

Despite the knowledge of many genetic alterations present in osteosarcoma, the complexity of this disease precludes placing its biology into a simple conceptual framework. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays important roles in downregulating T-cell activation, thereby attenuating anti-tumor responses and increasing cancer susceptibility. Polymorphisms in the CTLA-4 gene are associated with different autoimmune diseases and cancers. The current study evaluated the association of four CTLA-4 gene mutations, -1661A/G (rs4553808), -318C/T (rs5742909), +49G/A (rs231775), and CT60A/G (rs3087243), with osteosarcoma in the Chinese population. CTLA-4 polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 267 osteosarcoma patients and 282 age-matched healthy controls. Results showed that the CTLA-4 gene +49 AA genotype, +49 A allele, and GTAG haplotype were significantly more frequent in osteosarcoma patients than in controls (odds ratio [OR] 2.20, 95% confidence interval [CI] 1.23-2.95, p?=?0.007; OR 1.32, 95% CI 1.03-1.69, p?=?0.029, and OR?=?1.47, 95% CI 1.03-2.09, p?=?0.033, respectively). The CTLA-4 +49G/A polymorphism and GTAG haplotype are associated with increased risk of osteosarcoma.