Associations between interleukin 1 polymorphisms and susceptibility to systemic lupus erythematosus: A meta-analysis

Objective

This study determined whether interleukin 1 (IL1) polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE).

Methods

A meta-analysis was conducted on the associations between the IL1A, IL1B, and IL1 receptor antagonist (IL1RN) polymorphisms and SLE.

Results

A total of 15 studies involving 1956 SLE cases and 2347 controls were included in the meta-analysis. The meta-analysis showed an association between SLE and the IL1A −889 T allele in the overall population and Europeans (OR = 0.858, 95% CI = 0.737–0.986, p = 0.032; OR = 0.827, 95% CI = 0.687–0.994, p = 0.043). Meta-analysis of the IL1RN polymorphism revealed an association with SLE in all study subjects (OR for IL1RN^∗2 = 1.539, 95% CI = 1.266–1.871, p = 1.5 × 10⁻²) and in Europeans and Asians (OR = 1.483, 95% CI = 1.187–1.852, p = 0.001; OR = 1.787, 95% CI = 1.167–2.736, p = 0.008). No associations were found between SLE and the IL1B −511 C/T, 3953 C/T, and IL1A +4845 G/T polymorphisms.

Conclusions

This meta-analysis suggests IL1A −889 C/T polymorphism is associated with susceptibility to SLE in Europeans, and that the IL1RN^∗2 allele is associated with susceptibility to SLE in Europeans and Asians.     

Association between functional Fc receptor-like 3 (FCRL3) −169 C/T polymorphism and susceptibility to seropositive rheumatoid arthritis in Asians: A meta-analysis

Objective

The aim of this study was to determine whether the functional Fc receptor like-3 (FCRL3) −169 C/T polymorphism confers susceptibility to rheumatoid arthritis (RA).

Methods

A meta-analysis was conducted on the associations between the FCRL3 −169 C/T polymorphism and RA.

Results

A total of 17 comparison studies including 11,170 patients and 11,142 controls were considered in the meta-analysis. The meta-analysis showed no association between RA and the FCRL3 −169 C allele in study subjects (OR = 1.046, 95% CI = 0.997–1.098, p = 0.068). Stratification by ethnicity indicated an association between the FCRL3 −169 C allele and RA in Asians (OR = 1.101, 95% CI = 1.035–1.174, p = 0.002), but not in Europeans. Stratification of patients according to the presence of rheumatoid factor (RF) revealed a different significant association between the C allele and RA in RF-positive and RF-negative RA patients. Stratification by ethnicity indicated an association between the FCRL3 −169 C allele and RF-positive RA in Asians (OR = 1.093, 95% CI = 1.004–1.189, p = 0.040), but not in Europeans.

Conclusions

This meta-analysis demonstrates that the FCRL3 −169 C/T polymorphism may confer susceptibility to seropositive RA in Asians.     

Associations between interleukin-10 polymorphisms and susceptibility to systemic lupus erythematosus: A meta-analysis

Objective

The study determined whether interleukin-10 (IL-10) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE).

Methods

A meta-analysis was conducted on the associations between the IL-10-1082 G/A, -819 C/T, -592 C/A polymorphisms and the haplotype of the IL-10-1082 G/A, -819 C/T, -592 C/A polymorphisms and SLE.

Results

A total of 19 studies involving 2828 SLE patients and 4008 controls were considered in the meta-analysis. Meta-analysis of the IL-10-1082 G/A polymorphism revealed an association between SLE and the IL-10-1082 G allele (odds ratio [OR] = 1.158, 95% confidence interval [CI] = 1.051–1.276, p = 0.003). Stratification by ethnicity indicated an association between the IL-10-1082 G allele and SLE in Europeans (OR = 1.160, 95% CI = 1.039–1.296, p = 0.008). Meta-analysis stratified by ethnicity produced an association between the IL-10-819 C allele and SLE in Asians (OR = 1.308, 95% CI = 1.030–1.619, p = 0.027). Meta-analysis of the homozygous GCC/GCC haplotype failed to show a significant association with SLE in Europeans (OR = 1.223, 95% CI = 0.981–1.526, p = 0.074). However, meta-analysis of the GCC haplotype revealed a significant association with RA in all study subjects (OR = 1.402, 95% CI = 1.001–1.964, p = 0.049). Stratification by ethnicity indicated an association between the GCC haplotype and SLE in Europeans (OR = 1.656, 95% CI = 1.087–2.523, p = 0.019), but not in Asians (OR = 1.100, 95% CI = 0.703–1.721, p = 0.677). Meta-analysis of homozygous ATA/ATA haplotype failed to show a significant association with SLE in overall and European groups. However, meta-analysis of the ATA haplotype revealed a significant association with SLE in all study subjects (OR = 1.516, 95% CI = 1.039–2.213, p = 0.031) and Asians (OR = 2.580, 95% CI = 2.086–3.192, p < 1 × 10⁻⁹), but not in Europeans (OR = 1.233, 95% CI = 0.816–1.862, p = 0.320).

Conclusions

This meta-analysis suggests that the IL-10 polymorphisms confer susceptibility to SLE in Europeans and in Asians.     

Association between CTLA-4 polymorphisms and susceptibility to Celiac disease: A meta-analysis

Objective

The study explored whether cytotoxic T lymphocyte antigen-4 (CTLA-4) polymorphisms confer susceptibility to Celiac disease (CD).

Methods

A meta-analysis was conducted on the associations between the CTLA-4 CT60 A/G, +49 A/G, −318 C/T polymorphisms and CD using allele contrast, a recessive model, a dominant model, and homozygote contrast.

Results

Thirteen separate comparison studies were considered in the meta-analysis consisting of 5072 patients with CD and 13,462 controls. All subjects were Europeans. Meta-analysis of the CTLA-4 CT60 A/G polymorphism showed an association between CD and the CTLA-4 CT60 G allele in all subjects [Odds ratio (OR) = 1.160, 95% Confidence interval (CI) = 1.104–1.219, p < 1.0 × 10⁻⁹). Meta-analysis using the recessive model also revealed an association between CD and the CTLA-4CT60 GG genotype (OR = 1.331, 95% CI = 1.093–1.620, p = 0.004). Furthermore, analyses using the dominant model and homozygote contrast showed the same pattern as that shown by the CTLA-4CT60 G allele. Meta-analysis of the CTLA-4 +49 A/G polymorphism showed no association between CD and the CTLA-4 +49 G allele in all subjects (OR = 0.992, 95% CI = 0.872–1.129, p = 0.907). Meta-analysis using the recessive, dominant model, and homozygote contrast showed the same pattern as that shown by the CTLA-4 +49 Gallele. Meta-analysis of the CTLA-4 −318 C/T polymorphism showed no association between CD and the CTLA-4 −318 T allele in all subjects (OR = 1.018, 95% CI = 0.813–1.275, p = 0.877).

Conclusions

The CTLA-4 CT60 A/G polymorphism was associated with CD susceptibility, but no association was found between CTLA-4 +49 A/G and −318 C/T polymorphisms and CD in Europeans.     

CTLA-4 polymorphisms and susceptibility to inflammatory bowel disease: A meta-analysis

Objective

The aim of this study was to explore whether the cytotoxic T lymphocyte associated antigen-4 (CTLA-4) polymorphisms are associated with susceptibility to ulcerative colitis (UC) and Crohn’s disease (CD).

Methods

The authors conducted a meta-analysis on associations between CTLA-4 +49 A/G, −318 C/T, CT60 A/G polymorphisms, and (AT)n repeat in the 3′ untranslated region (UTR) and UC and CD susceptibility.

Results

A total of 15 comparison studies were considered in our meta-analysis. Meta-analysis revealed no association between UC and the CTLA-4 +49 G and CTLA-4 −318 T alleles in all subjects (OR = 0.982, 95% CI = 0.851–1.1339, p = 0.804; OR = 0.500, 95% CI = 0.223–1.124, p = 0.094). No association was found between UC and the CTLA-4 CT60 A/G polymorphism in Europeans. However, a significant association was observed between the longer allele (?118 bp) of the (AT)n and UC in Asian population (OR = 6.073, 95% CI = 4.246–8.684, p = 1.0 × 10⁻⁹). Meta-analysis of the CTLA-4 +49 A/G, −318 C/T, CT60 A/G polymorphisms showed no association with CD.

Conclusions

This meta-analysis demonstrates that the CTLA-4 (AT)n repeat in 3′ UTR may be associated with susceptibility to UC in Asians, while no association was found between the CTLA-4 +49 A/G, −318 C/T, and CD60 A/G polymorphism and susceptibility to UC and CD.     

SNP/haplotype associations of CCR2 and CCR5 genes with severity of chagasic cardiomyopathy

Background

Chronic inflammation plays a major role in the tissue injury seen in the chronic chagasic cardiomyopathy. The CCR2 and CCR5 chemokine receptors are involved with the type of cellular infiltrate present in cardiac tissue and CCR5-gene variants were previously associated with this pathology.

Methods and results

This is a replication study in an independent cohort with larger sample size. Nine SNPs of CCR5 and CCR2 were typified to confirm the association previously found with Chagas disease. Evidence of association with severity was found for the A allele of rs1799864 of CCR2 (p_ad = 0.02; OR = 1.91, 95% CI = 1.10–3.30), the T allele of the rs1800024 of CCR5 (p_ad = 0.01; OR = 1.95, 95% CI = 1.13–3.38), and the HHF^∗2 haplotype (p = 0.03, OR = 1.65, 95% CI = 1.03–2.65). These results were replicated in the study combined with previous data. In this analysis it was replicated the allele T of rs2734648 (p_ad = 0.009, OR = 0.52, 95% CI = 0.32–0.85) with protection. In addition, the allele G of rs1800023 (p_ad = 0.043, OR = 0.61, 95% CI = 0.38–0.98), and the HHC haplotype (p = 0.004, OR = 0.62, 95% CI = 0.44–0.86) were also associated with protection. In contrast, the allele A of rs1799864 of CCR2 (p_ad = 0.009; OR = 1.90, 95% CI = 1.17–3.08); and the allele T of rs1800024 of CCR5 (p_ad = 0.005, OR = 1.98, 95% CI = 1.22–3.23) were associated with greater severity. No evidence of association between symptomatic and asymptomatic patients was observed.

Conclusions

These results confirm that variants of CCR5 and CCR2 genes and their haplotypes are associated with the severity but not with susceptibility to develop chagasic cardiomyopathy.     

Distribution of Killer cell immunoglobulin like receptor genes in end stage renal disease among North Indian population

Introduction

NK cell function is regulated by cell surface inhibitory and activating receptors including the C-type lectin receptors and Killer Immunoglobulin-like receptors (KIR). The effect of immune modulating cytokines produced by NK cells in the pathogenesis of end stage renal disease (ESRD) remained intriguing. In this regard the present study assesses the combinatorial association of KIR gene content and KIR receptor–HLA ligand in the North Indian ESRD patients.

Material and methods

KIR gene polymorphism as a susceptible marker in ESRD among 512 patients and 512 ethnically matched controls was analyzed. PCR-SSP based genotyping for KIR gene content and HLA-A, B, C typing was carried out.

Results

Significant difference in frequencies of KIR2DS1–HLA-C2 (p ? 0.0001, OR = 1.98, CI = 1.50–2.61), KIR2DS2–HLAC1 (p ? 0.0001, OR = 1.87, CI = 1.42–2.46), KIR3DS1–HLA-Bw4 (p = 0.0038, OR = 1.46, CI = 1.13–1.88) combinations for ESRD was found. In the combinatorial analysis Bw4⁺/3DL1⁻/3DS1⁺ (p ? 0.0001, OR = 4.90, CI = 2.75–8.71) and C1⁺/2DL2⁻/2DL3⁻/2DS2⁺/2DS3⁺ (p = 0.0037, OR = 2.50, CI = 1.35–4.63) showed risk association. KIR3DS1 was observed to be susceptible for all four primary kidney disease groups.

Conclusion

NK cell de-regulation due to HLA ligand binding KIR receptors may be involved in the patho-physiology of ESRD. Upon analyzing the data in this context it was found that C2/C2 donor might improve the clinical outcome of patients having C2 ligands.     

Impact of genetic polymorphisms on the pathogenesis of idiopathic achalasia: Association with IL33 gene variant

Aim

To investigate the association of single nucleotide polymorphisms (SNPs) of genes involved in the regulation of immune responses, IL33, IL1RL1, IL23R, and IL10, with idiopathic achalasia in an Italian cohort of patients.

Materials and methods

A panel of eleven polymorphisms were genotyped in 116 unrelated idiopathic achalasic patients and 371 healthy subjects, by using TaqMan genotyping assays.

Results

Significant differences of allele (P = 0.0065, OR = 1.59, CI = 1.14–2.22) and genotype (P = 0.0097, OR = 1.74, CI = 1.14–2.65) frequencies of the IL33 rs3939286 variant were found between achalasic patients and controls. No association of the other investigated SNPs was detected. No differences in genotype and allele distribution were found with respect to clinical characteristics of patients.

Conclusion

We provide for the first time an association between the risk of developing idiopathic achalasia and IL-33 variant, underling the role of cytokines and inflammatory mediators on the pathogenesis of the disease.     

The nuclear factor-kB functional promoter polymorphism is associated with endometriosis and infertility

Introduction

An aberrant immunologic mechanism has been suggested to be involved in the pathogenesis of endometriosis. Nuclear factor-kB (NF-kB) plays a key role in the immune and inflammatory response and modulates cell proliferation, apoptosis, adhesion, invasion, and angiogenesis in many cell types involved in the development of endometriosis. We hypothesized a possible relationship between the NFKB1 promoter regulatory polymorphism and endometriosis and/or infertility.

Methods

A genetic association study comprising 172 infertile women with endometriosis, 77 women with idiopathic infertility and 189 controls was performed. Detection of the −94 insertion/deletion ATTG (rs28362491) polymorphism in the NFKB1 gene was done using the RFLP–PCR (Restriction Fragment Length Polymorphism–Polymerase Chain Reaction) technique. The results were statistically analyzed, and a p-value <0.05 was considered significant.

Results

Single-marker analysis revealed a significant association between the −94 insertion/deletion ATTG polymorphism and endometriosis-related infertility (p = 0.014, OR = 1.47, 95% CI = 1.09–1.97), especially in moderate/severe disease cases. Considering the idiopathic infertility group, a significant association was also found (p = <0.001, OR = 2.01, 95% CI = 1.35–2.98), suggesting that the −94 insertion/deletion ATTG polymorphism is associated with endometriosis and/or infertility.

Conclusion

In the population sample studied, the −94 insertion/deletion ATTG polymorphism in the NFKB1 gene was positively associated both with moderate/severe endometriosis and idiopathic infertility.     

Predictors and moderators of outcome in different brief interventions for smoking cessation in general medical practice

Objective

To explore demographic-, health-, and smoking-related predictors and moderators of outcome in smokers who participated in two different brief smoking cessation interventions.

Methods

Data were acquired using a quasi-randomized controlled trial that tested the efficacy of computer-generated tailored letters and physician-delivered brief advice against assessment only. Daily smokers (n = 1499) were recruited from 34 general medical practices. We used Generalized Estimating Equation analyses to investigate the relationship between 6-month prolonged smoking abstinence assessed at 12-, 18-, and 24-month follow-ups and potential predictors and moderators.

Results

Female gender (OR = 1.49, 95% CI = 1.01–2.19), higher level of education (OR = 1.82, 95% CI = 1.18–2.82), intention to quit smoking (OR = 1.66, 95% CI = 1.16–2.38), and smoking cessation self-efficacy (OR = 1.30, 95% CI = 1.03–1.64) were positively, nicotine dependence (OR = 0.84, 95% CI = 0.76–0.94) and the presence of a smoking partner (OR = 0.60, 95% CI = 0.42–0.85) were negatively associated with smoking abstinence. Compared to assessment only, physician advice was less effective for people without an intention to quit smoking and for unemployed.

Conclusion

Smoking cessation interventions might be improved by tailoring them to demographic- and smoking-related variables which were identified as predictors in this study.

Practice implications

The results suggest that tailored letters are a more universally applicable brief intervention in general medical practice than physician advice.     

Four tumor necrosis factor alpha genes polymorphisms and periodontitis risk in a Chinese population

Background

Tumour necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of generalized aggressive periodontitis (AgP) and chronic periodontitis (CP). The objective of the present study was to evaluate the association of four TNF-alpha gene polymorphisms (−1031T/C, −857C/T, −308G/A and −238G/A) with susceptibility to AgP and CP in a Chinese population.

Methods

A hospital-based case-control study was conducted in in patients with CP (n = 180), AgP (n = 180) and healthy controls (n = 180). Gene promoter polymorphisms were analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay. Genotype and allele frequencies were analyzed using the chi-square test and logistic regression analysis.

Results

TNF-alpha −1031CC genotype was significantly higher [odds ratio (OR) = 2.36, 95% confidence interval (CI) = 1.03, 5.43; P = 0.04] in patients with CP compared with healthy controls. TNF-alpha −308AA genotype was significantly higher (OR = 2.71, 95% CI = 1.09, 6.73; P = 0.03) in patients with AgP compared with healthy controls. No association was found of TNF-alpha −857C/T and −238G/A polymorphisms with susceptibility to AgP or CP.

Conclusions

Our data demonstrated that TNF-alpha −1031CC genotype was a risk factor for CP, and that TNF-alpha −308AA genotype was a risk factor for AgP. But there is a lack of association of TNF-alpha −857C/T and −238G/A polymorphisms with susceptibility to AgP or CP in a Chinese population.     

−1154G/A and −2578C/A polymorphisms of the vascular endothelial growth factor gene in Tunisian Alzheimer patients in relation to β-amyloid (1–42) and total tau protein

Recent evidences indicate that polymorphisms within the promoter region of the vascular endothelial growth factor (VEGF) gene may elevate the risk for Alzheimer's disease (AD). To further investigate, we have analyzed association between promoter polymorphisms of the VEGF gene in 93 AD patients and age and sex matched 113 controls from Tunisian population. The distribution of genotype and allele frequencies of the VEGF (−2578C/A) and (−1154G/A) polymorphisms did not differ significantly between AD and control groups (p > 0.05). In the subgroup of ApoE ?4 carriers, the −2578A was observed to be significantly higher in the AD patients than in the control individuals. After adjusting the data by gender, age and the ApoE ?4 status using logistic regression, the −2578A allele was found to increase the risk for sporadic AD by 1.7-fold. The present study provides the evidence that the −2578A allele may be associated with the development of AD in the individuals with ApoE ?4 allele. In addition, AD patients carrying the −2578A allele had lower Aβ42 (p = 0.029) levels than those without this allele, particularly in subjects with ApoE ?4 allele.     

Fibulin-5 (FBLN5) gene polymorphism is associated with pelvic organ prolapse

Objective

FBLN5 encodes a key protein of elastic fiber matrix assembly and function that contributes to maintaining pelvic support and plays the important role in the pathophysiology of pelvic organ prolapse (POP). The aim of the study was to investigate whether there is an association between common single-nucleotide polymorphisms (SNPs) of the FBLN5 gene and POP.

Study design

A total of eleven tag SNPs of the FBLN5 gene were genotyped using the polymerase chain reaction with confronting two-pair primers (PCR-CTPP) in 210 patients with POP (stages III–IV) and 292 controls with no even minimal POP.

Results

We revealed significant associations of tag SNPs rs2018736 and rs12589592 with POP. The top association signal was found for SNP rs2018736 (protective effect for the minor allele A) in the entire set: p = 0.0026, OR = 0.42, 95% CI: 0.24–0.75; in the stratum with pelvic floor trauma: p = 0.0018, OR = 0.27, 95% CI: 0.11–0.64; and in the stratum with fetal macrosomia: p = 0.013, OR = 0.14, 95% CI: 0.03–0.71. The results of the haplotype analyses were consistent with the single SNP analysis. In the strata without perineal trauma and fetal macrosomia effects were non-significant, possibly, due to the smaller effect sizes.

Conclusions

Current data provide, for the first time, strong evidence that common SNPs of the FBLN5 gene are associated with POP especially after pelvic floor injury.     

Relationship between postmenopausal osteoporosis and the components of clinical sarcopenia

Purpose

The aim of the study was to determine the relationship between the components of clinical sarcopenia and osteoporosis in postmenopausal women.

Methods

A population-based cohort of 590 Finnish postmenopausal women (mean age 67.9; range 65–72) was selected from the Osteoporosis Fracture Prevention (OSTPRE-FPS) study in 2002. Bone mineral density (BMD) and lean tissue mass were assessed by dual X-ray absorptiometry (DXA). The study sample was divided into three categories according to the WHO BMD classification: normal, osteopenia and osteoporosis. The study sample was divided into non-sarcopenic, presarcopenic, sarcopenic and non-classified groups according to quartiles of RSMI i.e. relative skeletal muscle index (appendicular muscle mass (kg)/square of height (m)), hand grip strength (kPa) and walking speed.

Results

In logistic regression analysis sarcopenic women had 12.9 times higher odds of having osteoporosis (p ≤ 0.001, OR = 12.9; 95% CI = 3.1–53.5) in comparison to non-sarcopenic women. In comparison to women in the highest grip strength quartile, women within the lowest quartile had 11.7 times higher odds of having osteoporosis (p = 0.001, OR = 11.7; 2.6–53.4). Sarcopenic women had 2.7 times higher odds of having fractures than their non-sarcopenic counterparts (p = 0.005, OR = 2.732; 1.4–5.5). Sarcopenic women had also 2.1 times higher risk of falls during the preceding 12 months compared to non-sarcopenic women (p = 0.021, OR = 2.1; 1.1–3.9). Adjustment for age, body mass index (BMI), physical activity and hormone therapy (HT) did not significantly alter these results.

Conclusions

The components of clinical sarcopenia are strongly associated with osteoporosis. Grip strength is the most significant measurement to reveal the association between sarcopenia and osteoporosis, falls and fractures.     

Genetic factors and multiple sclerosis in the Moroccan population: A role for HLA class II

Background and objective

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system that mainly affects young adults. The association between susceptibility to MS and HLA class II genes, in particular the DRB1*15 allele, has been reported in diverse ethnic groups. The aim of our study was to investigate the distribution of HLA-DRB1* and -DQB1* alleles in Moroccan population and their implication in the susceptibility to the disease.

Methods

Fifty-seven MS patients were compared to 172 healthy controls unrelated to one another and matched by age, sex and ethnic origin. HLA class II (DRB1* and DQB1*) typing was performed by PCR-SSP and/or Luminex (PCR-SSO). Allelic and haplotypic frequencies, P-values, odds ratio (OR) and 95% confidence interval (CI) were calculated using the software SPSS.

Results

A significant increase of DRB1*15 allele frequency (17.6% vs 8.4%, OR = 2.67, 95% CI = 1.36–5.23, P = 0.004) and HLA-DRB1*15-DQB1*06 haplotype (8.8% vs 4.08%, OR = 2.78, 95% CI = 1.41–5.48, P = 0.002) were observed in Moroccan MS patients. No association of the DR15 allele with sex or age at onset was appreciated. Concerning HLA-DQB1* alleles, no significant difference between patients and controls was found.

Conclusions

Our results reveal a role for HLA-DRB1*15 allele molecules in the predisposition of Moroccan patients to MS. Although this study should be confirmed on a larger sample size, it analyzes for the first time the possible role of a genetic marker for susceptibility to MS in Moroccan population.     

Psychological factors and subclinical atherosclerosis in postmenopausal Chinese women in Hong Kong

Background

Substantial evidence shows that psychological factors are associated with cardiovascular diseases. However, data on the association between psychological factors and subclinical atherosclerosis is lacking in postmenopausal Chinese women.

Objectives

To examine the associations of perceived stress and trait anxiety with subclinical atherosclerosis in postmenopausal Chinese women in Hong Kong. Their relationships with biological and behavioral risk factors were also examined.

Methods

Between 2002 and 2004, we recruited 518 postmenopausal women aged 50–64 years. Perceived stress and trait anxiety were evaluated by the perceived stress scale and the state-trait anxiety inventory, respectively. Subclinical atherosclerosis was determined by measuring carotid intima-media thickness (IMT) and plaque using B-mode ultrasonography.

Results

Perceived stress and trait anxiety showed no significant association with IMT or plaque. Multivariate analyses showed high perceived stress scores were associated with an increased risk of elevated total cholesterol (OR = 2.10; 95% CI = 1.17–3.77) and elevated low-density lipoprotein cholesterol (LDL-C) (OR = 2.39; 95% CI = 1.36–4.21). High trait anxiety scores were associated with a 2.7-fold risk of elevated LDL-C (OR = 2.74; 95% CI = 1.56–4.80). Women with high perceived stress or trait anxiety scores were more likely to be physically inactive.

Conclusions

Perceived stress and trait anxiety were associated with atherogenic lipid levels, but not subclinical atherosclerosis. Maintaining high physical activity may help alleviate psychological stress and anxiety.     

Association of CTLA-4 variants with susceptibility to inflammatory bowel disease: A meta-analysis

Objective

The aim of this study was to determine whether CTLA-4 gene variants were associated with susceptibility to inflammatory bowel disease (IBD).

Methods

Meta-analysis was conducted on the association between CTLA-4 variants and IBD using: (1) allelic contrast, (2) the recessive model, and (3) the dominant model.

Results

A total of 9 relevant studies including 1739 Crohn’s disease (CD) cases, 10 relevant studies containing 1017 ulcerative colitis (UC) cases and 2685 healthy controls were involved in this meta-analysis. Overall, CTLA-4+49A/G, −318C/T and CT60 variants were not associated with IBD susceptibility in all genetic models (P > 0.05). Stratification by ethnicity indicated a significant association between the CTLA-4+49A/G variant and CD in Caucasian group (GG vs. GA + AA: OR = 0.723, 95% CI = 0.564–0.926, P = 0.010). In Asian group, meta-analysis showed a significant association between the CTLA-4 CT60 variant and UC (AA vs. AG + GG: OR = 0.375, 95% CI = 0.163–0.861, P = 0.021).

Conclusions

Based on the published literature, this meta-analysis suggests that the CTLA-4+49A/G variant may be related to CD susceptibility in Caucasians, and the CTLA-4 CT60 variant may be associated with UC susceptibility in Asians.     

Association between interleukin-8 gene −251 T/A polymorphism and the risk of peptic ulcer disease: A meta-analysis

It remains controversial regarding the association between interleukin-8 (IL-8) gene −251 T/A polymorphism and peptic ulcer disease (PUD) risk. Thus, a large-scale meta-analysis evaluating the precise association between this gene variant and PUD risk is required. We searched the PubMed, Embase, Web of Science, and Google Scholar until April 25, 2012. Additionally, hand searching of the references of identified articles were performed. All the statistical tests were performed using Stata 11.0. A total of eight studies (3105 subjects) were included in this meta-analysis. Overall, no significant association was found between IL-8 gene −251 T/A polymorphism and PUD risk (for A allele vs. T allele: OR = 1.17, 95% CI = 0.97–1.41, p = 0.094; for A/A vs. T/T: OR = 1.33, 95% CI = 0.94–1.90, p = 0.108; for A/A vs. A/T + T/T: OR = 1.22, 95% CI = 0.97–1.52, p = 0.083; for A/A + A/T vs. T/T: OR = 1.26, 95% CI = 0.95–1.67, p = 0.113). However, in the subgroup analyses by ethnicity, H. pylori infection and the subtype of PUD, significant associations were found between IL-8 gene −251 T/A polymorphism and PUD risk in Asians, H. pylori+, duodenal ulcer disease (DUD) and gastric ulcer disease (GUD), respectively. In summary, the present meta-analysis suggests that IL-8 gene −251 T/A polymorphism is associated with increased PUD risk among Asians, and especially for the subgroups of H. pylori+, DUD and GUD.     

Association between two single nucleotide polymorphisms of PDCD6 gene and increased endometriosis risk

Programmed cell death 6 (PDCD6), a calcium binding protein of the penta EF-hand protein family, and its receptors are involved in regulation of apoptosis pathways. To evaluate the relationship between genetic polymorphisms of PDCD6 gene and endometriosis (ED) risk, we investigated the association of two single nucleotide polymorphisms (SNPs) of PDCD6 gene (rs4957014 and rs3756712) in 220 endometriosis patients and 386 unrelated healthy controls. The genotypes of these two SNPs were determined by using polymerase chain reaction (PCR)–restriction fragment length polymorphism (RFLP) and DNA sequencing methods. Significantly increased endometriosis risk was observed to be associated with G allele of rs4957014 locus (OR = 1.31, 95% CI = 1.03–1.69). We have also observed increased ED risk was statistically associated with rs4957014 polymorphism in a dominant model (OR = 1.52, 95% CI = 1.09–2.13). Although no association has been found between ED risk and the allele frequencies of rs3756712 locus (a marginal P = 0.066, OR = 1.27, 95% CI = 0.98–1.65), but in a dominant model, increased endometriosis risk was significantly associated with rs3756712 polymorphism (OR = 1.54, 95% CI = 1.11–2.17). In conclusion, the current study indicates that PDCD6 gene may be a new susceptibility gene to endometriosis.