A meta-analysis of the relationship between MYO9B gene polymorphisms and susceptibility to Crohn’s disease and ulcerative colitis

ObjectiveBoth Crohn’s disease (CD) and ulcerative colitis (UC) have a complex etiology involving multiple genetic and environmental factors. Multiple UC and CD susceptibility genes have been identified through genome-wide association studies and subsequent meta-analyses. The aim of this meta-analysis was to clarify the impact of MYO9B gene polymorphisms on CD and UC risk.MethodsThe PubMed, Elsevier Science Direct and Embase databases were searched to identify eligible studies that were published before October 2014. Data were extracted and pooled crude odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.ResultsA total of 11 studies, containing 3297 CD cases, 3903 UC cases and 8174 controls were included in this meta-analysis. Bonferroni correction results showed that rs1545620 A/C polymorphism of MYO9B gene was associated with both CD and UC susceptibility in Caucasians (OR = 0.88, 95% CI = 0.82 ∼ 0.95, P = 0.001; OR = 0.82, 95% CI = 0.76 ∼ 0.89, P < 0.001), but not in Chinese. rs1457092 G/T and rs2305764 C/T polymorphisms are associated with UC susceptibility (OR = 0.85, 95% CI = 0.79 ∼ 0.91, P < 0.001; OR = 0.88, 95% CI = 0.83 ∼ 0.93, P < 0.001), but not with CD susceptibility in Caucasians.ConclusionsThis meta-analysis suggested that rs1545620 is both CD and UC susceptible locus in Caucasians; rs1457092 and rs2305764 are UC susceptible loci, but are not CD susceptible loci in Caucasians. Further studies with more sample size are needed for a definitive conclusion.     

FCεRI gene promoter polymorphisms and total IgE levels in susceptibility to atopic dermatitis in Korea

IgE-dependent activation of mast cells and basophils through the high-affinity IgE receptor (FcεRI) is involved in the pathogenesis of allergen-induced immune responsiveness in atopic diseases like atopic dermatitis (AD). We sought to determine FcεRI gene polymorphisms are associated with AD in Korean patients, and analyzed the relevance of FcεRI gene polymorphisms and serum IgE levels. We conducted a case-control association analysis (175 patients and 56 controls) of Korean subjects. Genotyping was performed using the TaqMan fluorogenic 5' nuclease assay, and serum levels of IgE were measured using a fluorescence enzyme immunoassay. We found that there were no significant relationships between FcεRI and AD, although there were trends towards an association between the 66T>C (rs2251746) polymorphism and total serum IgE levels in the Korean AD patients. In conclusion, while the 66T>C (rs2251746) of the FcεRIα polymorphism may be linked to AD and higher serum IgE levels, polymorphisms in the FcεRIβ gene did not confer susceptibility to AD in our patient sample.     

Association between rs6887695 and 3′-untranslated region polymorphisms within the interleukin-12B gene and susceptibility to autoimmune diseases in Asian and European population: A meta-analysis

Background: The associations between rs6887695 and 3′-untranslated region (3′-UTR) single-nucleotide polymorphisms (SNPs) within interleukin-12B (IL-12B) and autoimmune diseases (ADs) remain controversial and inconclusive. The aim of this study was to evaluate the association between IL-12B (3′-UTR A/C and rs6887695 C/G SNPs) and ADs by meta-analysis. Methods: PubMed and EMBASE were exhaustively searched for studies on the association between IL-12B SNPs and ADs. Publication bias was examined by a funnel plot and Egger’s test. The robustness of the pooled results was assessed by sensitivity analysis. A fixed- or a random-effects model was applied to calculate the pooled odds ratios (ORs). Results: A total of 34 studies were included in this meta-analysis. The pooled results demonstrated that IL-12B rs6887695 SNPs were significantly associated with the risk of ADs. However, there was no significant association between IL-12B 3′-UTR SNPs and ADs. When the studies were stratified by ethnicity, significant association between IL-12B 3′-UTR SNPs and ADs was observed in both Asian and European population. In addition, allele A within 3′-UTR of IL-12B gene was found to be a protective factor for T1DM, but a risk factor for psoriasis. Conclusion: The IL-12B 3′-UTR and rs6887695 SNPs are associated with susceptibility to ADs.     

Endosomal toll-like receptor gene polymorphisms and susceptibility to HIV and HCV co-infection – Differential influence in individuals with distinct ethnic background

The genetic background of human populations can influence the susceptibility and outcome of infection diseases. Toll-like receptors (TLRs) have been previously associated with susceptibility to human immunodeficiency virus (HIV) infection, disease progression and hepatitis C, virus (HCV) co-infection in different populations, although mostly in Europeans. In this study, we investigated the genetic role of endosomal TLRs on susceptibility to HIV infection and HCV co-infection through the analysis of TLR7 rs179008, TLR8 rs3764880, TLR9 rs5743836 and TLR9 rs352140 polymorphisms in 789 Brazilian individuals (374 HIV+ and 415 HIV?), taking into account their ethnic background. Amongst the 357 HIV+ individuals with available data concerning HCV infection, 98 were positive. In European descendants, the TLR9 rs5743836 C carriers displayed a higher susceptibility to HIV infection [dominant, Odds Ratio (OR) = 1.53; 95% CI: 1.05–2.23; P = 0.027]. In African descendants, TLR9 rs5743836 CT genotype was associated with protection to HIV infection (codominant, OR = 0.51; 95% CI: 0.30–0.87; P = 0.013). Also, the TLR9 rs352140 AA variant genotype was associated with susceptibility to HIV+/HCV+ co-infection in African descendants (recessive, OR = 2.92; 95% CI: 1.22–6.98, P = 0.016). These results are discussed in the context of the different ethnic background of the studied individuals highlighting the influence of this genetic/ethnic background on the susceptibility to HIV infection and HIV/HCV co-infection in Brazilian individuals.     

Relationship between single nucleotide polymorphisms in the 3’-untranslated region of the vascular endothelial growth factor gene and susceptibility to diabetic peripheral neuropathy in China

Introduction

This study is to elucidate the relationship between a 936C/T mutation at the 3’-untranslated region of the human vascular endothelial growth factor (VEGF) gene and diabetic peripheral neuropathy (DPN).

Material and methods

All subjects recruited in this study were divided into DM (diabetes without neuropathy, retinopathy or nephropathy), DPN (diabetes with peripheral neuropathy only) and healthy control groups. The gene polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism, as well as other clinical methods including serum VEGF by ELISA.

Results

The C allele frequency and CC genotype frequency in the DPN group were higher than those in the NC group and DM group. The T allele frequency and CT+TT genotype (carrying the T allele) frequency in the DPN group were lower than those in the NC group (χ² = 19.051 and 18.533, both p < 0.001) and DM group (χ² = 11.117 and 11.156, both p = 0.001). However, there was no statistically significant difference in the three genotype (CC/CT+TT) frequencies and allele (C/T) frequencies between the DM group and the NC group. The multivariate logistic regression analysis showed that the levels of glycated hemoglobin (HbA_1c), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and plasma VEGF positively correlated with DPN, while the 936C/T gene polymorphism of VEGF negatively correlated with DPN.

Conclusions

Allele 936C of VEGF may serve as a genetic marker susceptible to DPN, while allele 936T may be a protective genetic marker of DPN.     

Associations between PTPN2 polymorphisms and susceptibility to ulcerative colitis and Crohn’s disease: a meta-analysis

Objective

Ulcerative colitis (UC) and Crohn’s disease (CD) result from an interaction between genetic and environmental factors. Though several polymorphisms have been identified in PTPN2, their roles in the incidence of UC and CD are conflicting. This meta-analysis was aimed to clarify the impact of these polymorphisms on UC and CD risk.

Method

PubMed, EMBASE, Cochrane Library and CBM were searched until 23 July 2013 for eligible studies on three PTPN2 polymorphisms: rs2542151, rs1893217 and rs7234029. Data were extracted, and pooled odd ratios (ORs) as well as 95 % confidence intervals (95 % CIs) were calculated.

Conclusion

The meta-analysis indicated that rs2542151, rs1893217 and rs1893217 were associated with increased CD risk, while the former was associated with increased UC risk. The differences in age of onset and ethnic groups may influence the associations. Gene–gene and gene–environment interactions should be investigated in the future.

Results

Seventeen studies with 18,308 cases and 20,406 controls were included. Significant associations were found between rs2542151 polymorphism and CD susceptibility (OR = 1.22, 95 % CI, 1.15–1.30, I ² = 32 %), as well as between rs2542151 and UC susceptibility (OR = 1.16, 95 % CI, 1.07–1.25, I ² = 39 %). A similar result was found in Caucasians, but not in Asians. Moreover, a significant increase in CD risk for all carriers of the minor allele of rs1893217 (OR = 1.45, 95 % CI, 1.23–1.70, I ² = 0 %) and rs7234029 (OR = 1.36, 95 % CI, 1.16–1.59, I ² = 0 %) were found. For children, the rs1893217 polymorphism appeared to confer susceptibility to CD (OR = 1.56, 95 % CI, 1.28–1.89, I ² = 0 %).     

Tagging single nucleotide polymorphisms in the PPAR-γ and RXR-α gene and type 2 diabetes risk:a case-control study of a Chinese Han population

Peroxisome proliferator-activated receptor (PPAR-γ),which is mainly involved in adipocyte differentiation, has been suggested to play an important role in the pathogenesis of insulin resistance and atherosclerosis. We investigated the frequencies of two common tagging polymorphisms of the PPAR-γ gene and two of PPAR-α with minor allele frequency (MAF)≥ 0.05 in the Chinese Han population and analyzed the correlation between the different genotypes and the risk of type 2 diabetes mellitus (T2DM). TaqMan assay was performed to test the genotypes in T2DM patients (n = 1,105) and normal controls (n = 1,107). Serum adiponectin concentration was measured by ELISA kit. The variant genotypes rs17817276GG, rs3856806CT and rs3856806CT/TT of PPAR-γ were associated with T2DM, P = 0.023,0.037 and 0.018, respectively. Furthermore, the prevalence of haplotype GT in PPAR-γ was less frequent in the case subjects (0.3%) than in the controls (1.9%) [P < 0.001,OR(95%CI)=0.13 (0.06-0.31)]. Patients with genotype TT of rs3856806 had a higher serum level of adiponectin than those with the genotype CC and CT (P = 0.031 and 0.038, respectively). There was no statistically significant difference between patients and controls in genotype distribution of rs6537944 and rs1045570 of the RXR-α gene. The present study suggests that the variant genotypes in the PPAR-γ gene could decrease the risk for the development of T2DM in the Chinese Han population.     

The association between the C-509T and T869C polymorphisms of TGF-β1 gene and the risk of asthma: A meta-analysis

Asthma is a complex multigenic disease in which gene–environment interactions play a critical role in disease onset and progression. Transforming growth factor-β1 (TGF-β1) is one of several candidate locus for the pathogenesis of asthma, and is highly polymorphic. To derive a more precise estimation of the relationship between the T869C and C-509T polymorphisms of the TGF-β1 gene and asthma, a meta-analysis of 24 published case–control studies was conducted. 20 studies for C-509T polymorphism and 8 studies for T869C polymorphism were included. The pooled odds ratios were calculated respectively for allele contrasts, additive genetic model, dominant genetic model and recessive genetic model. Subgroup analyses were also performed by ethnicity, age, atopic status and asthma severity for two gene polymorphisms. In regard to T869C polymorphism, significant associations with asthma were observed in recessive (OR 1.23, 95%CI 1.00–1.51 and P = 0.047), additive and allele models. In the subgroup analysis by age, significant risks were also found in the recessive model for adults (OR 1.31, 95%CI 1.02–1.69 and P = 0.032), atopic asthma (OR 1.63, 95%CI 1.07–2.49 and P = 0.023). With respect to C-509T polymorphism, significant associations with asthma were demonstrated in the overall analysis and subgroup analyses in the dominant model for Asian (OR 1.37, 95%CI 1.04–1.81 and P = 0.025), Adults (OR 1.26, 95%CI 1.02–1.56 and P = 0.035), Children (OR 1.19, 95%CI 1.01–1.40 and P = 0.034). Potentially functional TGF-β1 C-509T and T869C polymorphisms may be risk factors for asthma susceptibility.     

The androgen receptor CAG and GGN repeat polymorphisms and prostate cancer susceptibility in African-American men: results from the Flint Men’s Health Study

Repeat lengths of the CAG and GGN microsatellites in exon 1 of the androgen receptor (AR) gene have been hypothesized to be associated with prostate cancer risk. In vitro studies have showed an inverse association between AR CAG and GGN repeat length and activity levels of the AR product. It is known that men of African descent have a higher incidence of and greater mortality from prostate cancer than men of Caucasian or Asian descent and, on average, a smaller number of repeats at AR CAG and GGN. Consistent with these findings, studies have also found increased AR protein expression levels in benign prostatic hyperplasia and prostatic diseased tissues from men of African descent. Despite these findings, limited studies have been conducted to evaluate the association between repeat lengths at AR CAG and prostate cancer risk in African Americans. Our study is the first such study to examine whether repeat length of the AR GGN repeat is associated with prostate cancer risk in African Americans. We found no evidence for an association between AR CAG or GGN repeat lengths and prostate cancer risk in a population-based sample of African Americans.     

Association study between 834+7G/A and +1332C/T polymorphisms in the growth arrest specific 6 gene and risk of severe preeclampsia in Chinese population北大核心CSCD

Objective To investigate the relationship between polymorphisms of the growth arrest specific 6 (GAS6)gene and severe preeclampsia in a South West Han Chinese population. Methods Blood samples from 167 patientswith severe preeclampsia and 312 normal pregnant women as controls from Han Chinese in Chengdu area wereanalyzed by polymerase chain reaction-restriction fragment length polymorphisms. Results C and T allelefrequencies for +1332C/T site were 85. 63% and 14. 37% in the patient group, respectively, and 78. 04% and 21.96% in control group, respectively. The TT genotype and variant T allelic frequencies of the + 1332C/Tpolymorphism were significantly lower in patients with severe preeclampsia than in the control group (both P< 0. 05), and the odds ratio for the risk of severe preeclampsia was 0. 602 (95% CI: 0. 401-0. 904) incarriers for the variant T allele (x2 = 6. 045, P = 0.014). G and A allele frequencies for 834 +7G/A site were 72. 75% and 27. 25% in case group, respectively, and 74. 36% and 25. 64% in control group,respectively. The genotype and allele frequencies of the 834 + 7G/A polymorphism in patients with severe preeclampsia and controls showed no significant differences (both P>0. 05). In addition, there was no significant association between the polymorphisms and blood pressure levels in the patient or control groups. Conclusion The variant GAS6 +1332 T allele is associated with a decreased risk for severe preeclampsia in a South West Han Chinese population. On the other hand, the 834 + 7G/A polymorphism has no effect on the severe preeclampsia.     

Association between tumor necrosis factor-α gene polymorphisms and diffuse large B-cell lymphoma in Chinese Han population: evidence from two center case-control study and a meta-analysis

Objectives: The tumor necrosis factor-α (TNF-α) gene, which plays crucial roles in tumorigenesis, is reported to be an independent marker for cancer. This study aims to examine the association between the TNF-α G308A polymorphism and DLBCL risk based on the two center case-control studies and meta-analysis. Methods: In the current study, we performed a two centers case-control study to investigate the effect of the TNF-α G308A polymorphism on DLBCL risk in Chinese Han population. A meta-analysis including 10 published datasets along with current dataset, including 111 comparisons containing 34,041 cases and 42,730 controls were enrolled, was next performed to further confirm the association after literature search was conducted and relevant studies were identified from PubMed, Embase, and Web of Science. Results: The TNF-α -308A allele was associated with a significantly increased DLBCL risk in the two independent patient case-control studies and additionally for pooled analysis from the two sets (P<0.05 for both). The result of meta-analysis further demonstrated that the A allele of -308A was significantly correlated with DLBCL risk under the allelic model (OR=1.35, 95% CI=1.27-1.44) without heterogeneity by fixed-effects model analysis (Q=17.30, P=0.139). Moreover, sensitivity analysis supported the robustness of this meta-analysis. Conclusion: This study suggested that -308A polymorphism may be associated with the susceptibility of DLBCL in a Chinese population. The further meta-analysis provides additional evidence supporting the above result that the risk allele of the -308A polymorphism may increase DLBCL risk.     

Social support and behavior in a stressful situation in relation to myocardial infarction and mortality: who is at risk? results from prospective cohort study “men born in 1914,” malmö, sweden

Coronary heart disease remains an important cause of morbidity and mortality. Much data support the view that social support is associated with coronary heart disease. Participants of the study “Men born in 1914,” (414 men) were followed from a baseline measurement in 1982/83 until the end of 1996. At baseline, the men answered a questionnaire on social support and participated in a stressful test where their behavior was categorized as adaptive or maladaptive. This study examined whether social support had a prospective impact on the incidence of myocardial infarction and all-cause mortality when behavior in the stressful task was taken into consideration. The conclusion of the study was that unsatisfactory levels of social support is associated with an increased risk of incident myocardial infarction (HR 2.40, CI 1.36-4.25, p = .003) and premature death (HR 1.99, CI 1.32-3.00, p = .001) but only in men who had shown maladaptive behavior in the test.     

Polymorphisms in the human CYP1A1 gene as susceptibility factors for lung cancer: exon-7 mutation (4889 A to G), and a T to C mutation in the 3′-flanking region

Genetic differences in the metabolism of carcinogens may codetermine individual predisposition to cancer. Cytochrome P-4501A1 (CYP1A1) metabolically activates precarcinogens in cigarette smoke, such as benzo(a)pyrene, which is also an inducer of CYP1A1. Two point mutations have been reported, m1 in the 3-flanking region (6235T to C), and m2 within exon 7 (4889A to G), the latter leading to an isoleucine to valine exchange. In the Japanese population ml and m2 are correlated with lung cancer, suggesting an increased susceptibility to cigarette smoking related lung cancer. We studied 142 lung cancer and 171 reference patients in an ethnically homogeneous German group for m1 and m2 mutations by restriction fragment length polymorphism and allele-specific polymerase chain reaction, respectively. No statistically significant difference was found in the distribution of m1 alleles between lung cancer and controls; the frequency was 8.5% and 7.3% of the alleles, respectively (odds ratio = 1.17). A trend to an overrepresentation of ml alleles was observed among 52 squamous cell carcinoma patients (odds ratio = 1.65). In contrast, the frequency of m2 alleles in lung cancer patients was twofold higher (6.7%) than in the reference group (3.2%; odds ratio = 2.16; 95% confidence limits 0.96–5.11, P = 0.033); the odds ratio of m2 alleles in squamous cell carcinoma was 2.51 (95% confidence limits 0.85–7.05, P = 0.05). There was a close genetic linkage of m2 to m1 (10 of 11 reference patients), but a significantly higher number of cancer patients showed no linkage compared to the controls (odds ratio = 8.89, 95% confidence limits 0.83–433, P = 0.04). Thus no association was found between presence of ml alleles and lung cancer, but, in contrast, m2 alleles proved as a hereditary risk factor, especially if not linked with m1 alleles.Abbreviations Ah aryl hydrocarbon - CYP1A1 cytochrome P4501A1 - CYP1A1 CYP1A1 gene - PCR polymerase chain reaction - PY pack years - RFLP restriction fragment length polymorphism Correspondence to: N. Drakoulis