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.     

Association study between the −1021C/T polymorphism of the dopamine-β-hydroxylase gene promoter and personality traits in healthy subjects

Dopamine and norepinephrine are implicated in the characterization of personality traits. Dopamine-β-hydroxylase (DBH) is the enzyme responsible for conversion of dopamine to norepinephrine, and thus plays an important role in controlling dispositions of these neurotransmitters. Previous studies have shown that the −1021C/T polymorphism of the DBH gene promoter influences plasma DBH activity. Therefore, we examined the association between the −1021C/T DBH polymorphism and personality traits in 627 Japanese healthy volunteers. The DBH genotypes were identified by a PCR-RFLP method, and personality traits were assessed by the Temperament and Character Inventory (TCI). In the two-factor analysis of covariance with the DBH genotype and sex as factors and with age as a covariate, there was no main effect of the DBH genotype on any TCI score, while the interaction between the factors was significant in harm avoidance. In the post hoc analysis, the group with the T allele predictive of lower DBH activity had higher scores of harm avoidance than that without the T allele in females (p = 0.006), but not in males. The present study suggests that the −1021C/T DBH polymorphism affects the personality trait of harm avoidance in healthy females.     

Association between interleukin-1β C (3953/4)T polymorphism and chronic periodontitis: Evidence from a meta-analysis

The aim of this study was to perform a meta-analysis to evaluated the association between interleukin-1β (IL-1β) C(3953/4)T polymorphism and chronic periodontitis (CP). Systematic searches of electronic databases and hand searching of references were performed, including PubMed, Embase and Web of Science. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. Publication bias was tested by Begg’s funnel plot and Egger’s regression test. Sensitivity analysis was conducted by limiting the meta-analysis studies conforming to Hardy–Weinberg equilibrium (HWE) or high quality (score ? 7). Data analyses were carried out by Stata 11.0. There were significant associations between IL-1β C(3953/4)T polymorphism and CP (for T allele vs. C allele: OR = 1.30, 95%CI = 1.05–1.60, p = 0.02; for T/T vs. C/C: OR = 1.66, 95%CI = 1.12–2.45, p = 0.01; for C/T + T/T vs. C/C: OR = 1.28, 95%CI = 0.99–1.65; and for T/T vs. C/T + C/C: OR = 1.62, 95%CI = 1.15–2.29, p = 0.006). When stratified by ethnicity, statistically significantly elevated risk was found for Caucasians, but not for Asians. When stratified by study design, evidences of significant association was observed between IL-1β C(3953/4)T polymorphism and CP in both population-based studies and hospital-based studies. This meta-analysis indicates that there is strong evidence for association between IL-1β C(3953/4)T polymorphism and CP.     

Genetic association between p73 G4C14–A4T14 polymorphism and risk of squamous cell carcinoma

This study is to evaluate the association between p73 G4C14–A4T14 polymorphism and squamous cell carcinoma (SCC) risk in diverse populations. We searched the PubMed, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine databases for all articles on the association between p73 G4C14–A4T14 polymorphism and SCC risk through March 2014. We performed a comprehensive meta-analysis of six case–control studies that included 1,758 SCC cases and 2,970 case-free controls. All analyses were performed using STATA 11.0, using two-sided P values. Overall, this meta-analysis showed that the p73 G4C14–A4T14 polymorphism was associated with a significantly increased risk of SCC in three genetic models. However, after excluding one study deviating from Hardy–Weinberg equilibrium, the results then demonstrated that the p73 G4C14–A4T14 polymorphism was only associated with elevated risk of cervical squamous cell carcinoma (for AT/GC vs GC/GC: OR 1.51, 95 % CI 1.14–2.00, P _{heterogeneity} = 0.996; for AT/AT+AT/GC vs GC/GC: OR 1.42, 95 % CI 1.08–1.87, P _{heterogeneity} = 0.994) in subgroup analysis by tumor sites. No publication bias was found in the present study. This meta-analysis suggests that the p73 G4C14–A4T14 polymorphism is associated with an increased risk of cervical squamous cell carcinoma. Further large and well-designed studies are needed to confirm this association.     

No evidence for association between 1858 C/T single-nucleotide polymorphism of PTPN22 gene and primary Sjögren's syndrome

One-third of first-degree relatives of patients with primary Sj?gren's syndrome (pSS) suffer from other autoimmune diseases, including type I diabetes, systemic lupus erythematosus and autoimmune thyroiditis. Recently, 1858 C/T polymorphism of PTPN22 gene was reported to predispose to these autoimmune diseases. We decided to investigate whether PTPN22 gene polymorphism was also involved in the genetic predisposition to pSS in a case-control study, including 183 patients with pSS and 172 healthy controls. No significant differences in allele (T allele frequency: 7.7% in patients with pSS vs 7.8% in controls, P=0.9) and genotype frequencies of PTPN22 polymorphism were detected between patients with pSS and controls. PTPN 22 gene polymorphism was not associated with a specific pattern of autoantibody secretion either. Thus, 1858 C/T polymorphism of PTPN22 gene is not involved in genetic predisposition to pSS.     

The +874T/A polymorphism in the interferon-γ gene and tuberculosis risk: an update by meta-analysis

The +874T/A polymorphism in the interferon-γ (IFN-γ) gene has been extensively examined for association to tuberculosis (TB); however, results of different studies have been inconsistent. The aim of this study was to comprehensively analyze the genetic risk of the +874T/A polymorphism in IFN-γ gene for TB by meta-analysis. A total of 4553 cases and 4631 controls in 21 case-control studies were included in this meta-analysis. The results indicated that the variant T allele carriers had a 27% decreased risk of TB, when compared with the homozygote AA (odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.61-0.87 for TT + TA versus AA). In the subgroup analysis by ethnicity, significant decreased risks were associated with T allele carriers in Asians (OR= 0.71, 95% CI = 0.52-0.97, p = 0.03) but not in Caucasians (OR = 0.87, 95% CI = 0.65-1.17, p = 0.37). Our results suggest that the IFN-γ +874T/A polymorphism contributes to susceptibility to TB.     

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.     

Association of polymorphism +874 A/T of interferon-γ and susceptibility to the development of tuberculosis: meta-analysis

The immune defence against Mycobacterium tuberculosis is complex and involves multiple interacting cells. Studies in subjects with polymorphisms in genes for IFN or its receptor gene evaluate their relationship with mycobacterium infections. The purpose of this study was to analyze the evidence of the effect of polymorphism +874 A/T from interferon-γ on the occurrence of tuberculosis. We performed a meta-analysis of studies published between June 2002 and April 2012. The articles analyzed assessed the relationship between the polymorphism +874 A/T and the development of tuberculosis. The meta-analysis was performed with a random effect model, considering the heterogeneity among studies. Genotype TT showed a protective effect (OR, 0.77; 95% CI?=?0.67–0.88) while genotype AA may be associated with increased susceptibility to developing tuberculosis (OR, 1.51; 95% CI?=?1.38–1.65). In relation to alleles, we can verify that the A allele is related to the development of tuberculosis (OR, 1.56; 95% CI?=?1.42–1.71). This information reinforces the importance of host genetics in the development of infectious diseases. Studies in this area can result in the promotion of new and more accurate genetic markers.     

The association between the functional PTPN22 1858 C/T and MIF −173 C/G polymorphisms and juvenile idiopathic arthritis: a meta-analysis

Background  

The aim of this study was to determine whether the protein tyrosine phosphatase nonreceptor 22 (PTPN22) 1858 C/T (rs2476601) and macrophage migration inhibitory factor (MIF) −173 C/G polymorphisms confer susceptibility to juvenile idiopathic arthritis (JIA).     

Genetic association between the HIF-1α P582S polymorphism and cervical cancer risk: a meta analysis

Background: Hypoxia-inducible factor-1 alpha (HIF-1α) P582S polymorphism has been reported to increase transactivation capacity of HIF-1α, which is prone to tumorigenesis. Several published case-control studies on the association between P582S polymorphism and cervical cancer have shown mixed results. In this study, we chose to perform a meta-analysis to assess the association. Methodology/Principal findings: We conducted a meta-analysis consisting of four studies with a total of 846 cases and 991 controls. All data were collected and overall comparison was performed among all subjects. Using the fi xed effects model, the homozygous and the recessive models showed a significant increase in the risk of cervical cancer (the pooled OR=6.32, 95% CI=2.28-17.55, Phet=0.348; the pooled OR=5.86, 95% CI=2.13-16.11, Phet=0.394 respectively). Publication bias was not significantly indicated in this analysis. Conclusions: This meta-analysis demonstrates that HIF-1α P582S polymorphism may be associated with the risk of cervical cancer.     

The PD-1 rs36084323 A > G polymorphism decrease cancer risk in Asian: A meta-analysis

The rs36084323 A?>?G polymorphism in programmed cell death-1(PD-1) gene has been reported to be associated with cancer risk. However, the results of previous studies were inconsistent. Therefore, we performed a meta-analysis to identify the potential association, by searching the PubMed, EMBASE, Cochrane Library, and the Chinese CNKI, WANFANG and CBM databases. Data were extracted and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the strength of the association. A total of 10 relevant studies involving 4445 cancer cases and 5126 controls were recruited. Overall, the results indicated that the PD-1 rs36084323 A?>?G polymorphism was not statistically associated with cancer risk. However, stratified analysis revealed that there was a statistically reduced cancer risk in Asians(G vs. A, OR?=?0.89, 95%CI:0.81–0.97, P?=?0.008, I²?=?48.8%; GG vs. AA, OR?=?0.79, 95% CI:0.66–0.94, P?=?0.008, I²?=?48.7%; GG/AG vs. AA, OR?=?0.87, 95%CI:0.76–0.98, P?=?0.017, I²?=?34.9%; GG vs. AG/AA, OR?=?0.85, 95%CI:0.75–0.97, P?=?0.027, I²?=?40%) and in the patients with EOC(AG vs. AA, OR?=?0.69, 95%CI:0.54–0.90, P?=?0.005, I²?=?0%; GG/AG vs. AA, OR?=?0.67, 95%CI:0.52–0.85, P?=?0.001, I²?=?0). Meta-regression showed that ethnicity (P?=?0.029) but not cancer types (P?=?0.792), source of controls (P?=?0.207) or ample size (P?=?0.585) were the sources of heterogeneity. This meta-analysis demonstrates the PD-1 rs36084323 A?>?G polymorphism is associated with decreased cancer risk in Asian, and suggests it could potentially serve as a biomarker to screen high-risk individuals. Large-scale and well-designed case-control studies are needed to enrich the evidence of this result.     

The possible association between the presence of an MPO −463 G > A (rs2333227) polymorphism and cervical cancer risk

Purpose

The association between myeloperoxidase (MPO) polymorphism and the risk of cervical cancer is inconclusive. We performed a meta-analysis to clarify if a correlation exists between MPO polymorphism and the risk for developing cervical cancer.

Relationship between the polymorphism of tumor necrosis factor-α-308 G>A and susceptibility to inflammatory bowel diseases and colorectal cancer: a meta-analysis

Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are common health problems worldwide. Tumor necrosis factor (TNF) is a type of cytokine that induces inflammation and inhibits tumorigenesis. Several studies have assessed the relationship between the polymorphism of TNF-α-308 G>A and the susceptibility to IBD and CRC; however, the results have been controversial. In addition, the hypothesis whether the increased risk of CRC in IBD patients could be partly ascribed to the polymorphism of TNF-α-308 G>A was unclear. Therefore, we conducted this meta-analysis to confirm these associations. Pooled odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated on the basis of data from 14, 18, and 7 studies from a total of 27 studies for the associations between the polymorphism of TNF-α-308 G>A and ulcerative colitis, Crohn's disease (CD) and CRC. In Europeans, the AA genotype increased the risk of ulcerative colitis (UC) (OR, 2.041; 95% CI, 1.261-3.301) and CD (OR, 1.730; 95% CI, 1.168-2.564) significantly, without obvious heterogeneity and publication bias. Meanwhile, the GA genotype increased the risk of UC in Asians (OR, 2.360; 95% CI, 1.269-4.390) significantly. However, no significant association was observed for CRC in any ethnic population. The results of this meta-analysis suggested that the polymorphism of TNF-α-308 G>A participates in modifying the susceptibility to UC and CD in Europeans and Asians. The increased risk of CRC in IBD patients should be clarified as the combined effects of polymorphisms in TNF-α and other cytokines, and the interaction with environmental factors, in future studies.     

PTPN22 1858C > T polymorphism and susceptibility to systemic lupus erythematosus: a meta-analysis update

Studies performed in the past years showed PTNP22 1858?C?>?T (rs2476601) polymorphism as associated with systemic lupus erythematosus susceptibility, although conflicting findings are still found. In this context, a powerful statistical study, such as meta-analysis, is necessary to establish a consensus. The aim of this study was to evaluate association studies between the PTPN22 1858?C?>?T polymorphism and SLE by a meta-analysis update, including three recently published studies in the last three?years. A total of 3868 SLE patients and 7458 healthy individuals were considered herein, enclosing 19 studies from Asian, American, European and Latin ethnic groups. Odds ratio (OR) was performed for allelic, dominant and recessive genetic models. Statistically significant association was found between the PTPN22 1858?C?>?T polymorphism and susceptibility to SLE in all inheritance models. Allelic genetic model data (OR?=?1.54, 95% confidence interval (CI)?=?1.38–1.72, p value=.000) shows that T allele confers increased SLE susceptibility. As well as recessive genetic model (OR?=?2.04, 95% CI?=?1.09–3.82, p value?=?.030) for T/T genotype. Instead, dominant genetic model shows that C/C genotype confers lower susceptibility for SLE development (OR?=?0.62, 95% CI?=?0.54–0.72, p value?=?.000). In addition, we provided an ethnicity-derived meta-analysis. The results showed association in Caucasian (OR?=?1.47, p value?=?.000) and Latin (OR?=?2.41, p value?=?.000) ethnic groups. However, rs2476601 polymorphism is not associated nor in Asian (OR=?1.31; p value?=?.54) and African (OR?=?2.04; p value=.22) populations. In conclusion, present meta-analysis update confirms that T allele and T/T genotype in PTPN22 1858?C?>?T polymorphism confers SLE susceptibility, particular in Caucasian and Latin groups, suggesting PTPN22 1858?C?>?T as a potential genetic marker in SLE susceptibility.     

Interleukin-6-174G > C (rs1800795) polymorphism distribution and its association with rheumatoid arthritis: A case-control study and meta-analysis

The association of interleukin-6 (IL-6)-174G?>?C (rs1800795) single nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) is a relevant issue because of conflicting and consensus lacking reports published in literature. We investigated IL-6-174G?>?C promoter polymorphism in 34 RA patients, attending a tertiary care hospital in north India. We also performed a meta-analysis, of the previously published studies reporting this genetic relationship, in overall population, and independently in Asian and Caucasian ethnicities to further elucidate this association. A total of 13 studies, including the current one, involving 3291 RA cases and 3812 controls were analyzed. Out of the 13 studies, 6 were from Asian, 6 from Caucasian and 1 from a mixed population. Our case-control study showed significant association of IL-6-174G?>?C SNP with increased RA risk: allelic (OR?=?3.750, 95% CI?=?1.800–7.813, p?<?0.001); dominant (OR?=?2.800, 95% CI?=?1.167–6.721, p?=?0.021); and recessive (OR?=?36.72, 95% CI?=?2.004–672.7, p?=?0.015). The meta-analysis revealed the increased RA risk associated with IL-6-174G?>?C SNP in overall population: allelic (OR?=?1.650, 95% CI?=?1.169–2.329, p?=?0.004); homozygous (OR?=?1.380, 95% CI?=?0.906–2.101, p?=?0.133); heterozygous (OR?=?1.559, 95% CI?=?1.001–2.428, p?=?0.049); dominant (OR?=?1.663, 95% CI?=?1.078–2.567, p?=?0.022); and recessive (OR?=?1.366, 95% CI?=?0.964–1.935, p?=?0.079). Subgroup analysis also showed this polymorphism to be associated with increased RA risk in Asian population: allelic (OR?=?3.724, 95% CI?=?1.361–10.190, p?=?0.010); dominant (OR?=?3.823, 95% CI?=?1.320–11.074, p?=?0.013); and recessive (OR?=?4.357, 95% CI?=?1.634–11.623, p?=?0.003), but not in Caucasian population. This meta-analysis shows that IL-6-174G?>?C SNP is significantly associated with increased RA risk in overall, and specifically in Asian population.     

Genetic analysis of interleukin-1 receptor antagonist and interleukin-1β single-nucleotide polymorphisms C−511T and C+3953T in alopecia areata: susceptibility and severity association

The present study was aimed to explore the effect of two selected polymorphisms from interleukin-1β (IL-1β) gene [SNPs ?511 and +3953] and a variable number of tandem repeat (VNTR) from interleukin-1 receptor antagonist (IL-1RN) on the susceptibility and severity of alopecia areata (AA) in Kuwaiti subjects. IL-1β SNPs C?511T, C+3953T, and IL-1RN VNTR were screened in 96 alopecia patients classified clinically, according to the disease severity as patchy (P), semiuniversalis (SU), and universalis (U), and in 100 ethnically matched healthy controls. Polymerase chain reaction followed by restriction fragment length polymorphism and direct DNA sequencing were employed for genotyping. Comparing the stratified AA cases based on severity, IL-β SNP C?511T showed a significant association (genotype and allelotype levels p = 0.03 and p = 0.028, respectively). Genotype CC was 50 % more frequent in U cases than in P or SU. When P and SU were grouped and tested against U, a significant difference was observed (genotype and allelotype levels p = 0.006 and p = 0.008, respectively). Compared to genotype CT, carriers of IL-1β ?511 CC genotype showed an increased risk to develop severe AA (p = 0.004, OR = 4.14, 95 % CI = 1.61–10.69). Four alleles and genotypes (1/1, 1/3, 1/4, and 2/2) of IL-1RN VNTR were detected in AA patients while only two (1/1 and 1/3) in controls. IL-1RN VNTR showed genotype and allelotype association with AA (p = 0.05 and p = 0.025, respectively). Our results showed that IL-1β and IL-1RN VNTR are significantly associated with the susceptibility to alopecia areata. Allele C of the IL-β C?511T SNP is linked to the severe form of AA.     

Effect of transforming growth factor-β1 869C/T polymorphism and radiation pneumonitis

Background: The Transforming growth factor-β1 (TGFβ1) 869C/T polymorphism was associated with radiation pneumonitis (RP) susceptibility. However, the results remained controversial. Thus, a meta-analysis was conducted. Methods: Relevant studies were systematically searched by using the NCBI, Medline, Web of Science and Embase databases. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using random-effects models. Results: There was a significant association between TGFβ1 869C/T polymorphism and RP susceptibility (OR = 1.77; 95% CI, 1.27-2.47; P = 0.0007). Conclusion: This study suggested that TGFβ1 869C/T polymorphism was a risk factor of RP.     

Distribution of the − 13910C>T polymorphism in the general population of Portugal and in subjects with gastrointestinal complaints associated with milk consumption

Background: The ? 13910C>T polymorphism has been associated with lactase persistence (LP) in European populations.

Aim: To assess ? 13910C>T genotypes across Portugal and in adult individuals with unspecific gastrointestinal complaints associated with milk consumption.

Subjects and methods: This study genotyped ? 13910C>T in the general population from Northern (n = 64), Central (n = 70) and Southern (n = 65) Portugal and in 40 subjects with gastrointestinal symptoms. Additionally, the concordance was evaluated between breath-hydrogen test and ? 13910C>T genotypes in 65 samples.

Results: An overall frequency of 0.349 for the LP ? 13910*T allele was estimated in the general population, with a noticeable decrease in the South (0.269) compared with North (0.383) and Centre (0.393). Among the symptomatic group, the frequency of the ? 13910*T allele (0.363) was not significantly different from the general population. A 94% concordance was found between the breath-hydrogen and the molecular tests.

Conclusions: This study suggests that (i) the distribution of the LP polymorphism is not uniform across the country, (ii) genotyping ? 13910C>T is a good diagnostic tool for lactase status in the Portuguese population and (iii) self-reported gastrointestinal complaints are not good predictors of the LP status, implying that a significant part of those complaints may not be related to hypolactasia.