Association between Polymorphism of the Interleukin-13 Gene and Susceptibility to Hepatocellular Carcinoma in the Chinese Population

ObjectiveInterleukin-13 (IL-13) is a potent pleiotropic cytokine that is produced by activated CD4 T cells. This study was undertaken to determine the relationship between two IL-13 gene single nucleotide polymorphisms (SNP rs1800925 and SNP rs20541) and the incidence of hepatitis B virus-related (HBV) hepatocellular carcinoma (HCC).MethodThree hundred and ninety-eight HBV-positive individuals (192 HCC and 206 patients with chronic hepatitis) and one hundred and ninety-two healthy participants from the First Affiliated Hospital of Guangxi Medical University were enrolled in this study.ResultsThe results showed no significant differences between the genotype and allele frequencies of the IL-13 gene rs1800925 and rs20541 polymorphisms and chronic hepatitis B risk after adjusting for age, sex, tobacco use, and alcohol intake using binary logistic regression analyses. Regarding the rs20541 SNP, the GA genotype was significantly related to a decreased risk of HCC after adjusting for age, sex, tobacco use, and alcohol intake using binary logistic regression analyses (The odds ratio (OR) = 0.54, 95% confidence intervals (CI) 0.34–0.87). The adjusted OR for the GA and AA genotypes combined was 0.68 (95% CI 0.39–0.90).ConclusionThis study indicates that the functional IL-13 rs20541 polymorphism may contribute to the risk of HCC and that the rs20541 polymorphism is a protective factor for HCC.     

Association between polymorphisms in interleukin-4Rα and interleukin-13 and glioma risk: A meta-analysis

Introduction: It has been suggested that allergies are inversely associated with glioma risk. Single nucleotide polymorphisms in two allergy-related genes [interleukin (IL)-4Rα, IL-13] have been implicated in susceptibility to glioma; however, results from the published studies remained inconclusive. Methods: To derive a more precise relationship, we conducted a meta-analysis including seven case–control studies that investigated the influence of IL-4Rα rs1801275 and IL13 rs20541 polymorphisms on glioma risk. Data were extracted from these studies and pooled odds ratios (OR) with 95% confidence intervals (CI) were used to investigate the strength of the association. Results: Overall, the pooled analysis showed that there was no significant association between the IL-4Rα rs1801275 polymorphism and glioma risk (OR = 0.99, 95%CI: 0.79–1.25, AG/GG vs. AA). However, we found that the IL13 rs20541 variant genotypes (GA/AA) were significantly associated with reduced risk for glioma (OR = 0.85, 95%CI: 0.75–0.97, GA/AA vs. GG). In the stratified analyses by ethnicity, marginally significant association between the IL13 rs20541 polymorphism and decreased glioma risk was found among Asian populations in dominant models (OR = 0.84, 95%CI: 0.70–1.00, GA/AA vs. GG). Conclusions: This meta-analysis suggests that the IL13 rs20541 but not the IL-4Rα rs1801275 polymorphism may be a genetic predictor for glioma. More studies with larger sample size are warranted to further elucidate the impact of the IL13 rs20541 polymorphism on glioma risk.     

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.     

Differential allelic expression of IL13 and CSF2 genes associated with asthma

An important area of genetic research is the identification of functional mechanisms in polymorphisms associated with diseases. A highly relevant functional mechanism is the influence of polymorphisms on gene expression levels (differential allelic expression, DAE). The coding single nucleotide polymorphisms (SNPs) CSF2^rs25882 and IL13^rs20541 have been associated with asthma. In this work, we investigated whether the mRNA expression levels of CSF2 or IL13 were correlated with these SNPs. Samples were analyzed by mass spectrometry-based quantification of gene expression. Both SNPs influenced gene expression levels (CSF2^rs25882: p_overall = 0.008 and p_{DAE samples} = 0.00006; IL13^rs20541: p_overall = 0.059 and p_{DAE samples} = 0.036). For CSF2, the expression level was increased by 27.4% (95% CI: 18.5%–35.4%) in samples with significant DAE in the presence of one copy of risk variant CSF2^rs25882-T. The average expression level of IL13 was increased by 29.8% (95% CI: 3.1%–63.4%) in samples with significant DAE in the presence of one copy of risk variant IL13^rs20541-A. Enhanced expression of CSF2 could stimulate macrophages and neutrophils during inflammation and may be related to the etiology of asthma. For IL-13, higher expression could enhance the functional activity of the asthma-associated isoform. Overall, the analysis of DAE provides an efficient approach for identifying possible functional mechanisms that link disease-associated variants with altered gene expression levels.     

Importance of Fatty Acid Compositions in Patients with Peripheral Arterial Disease

Objective

Importance of fatty acid components and imbalances has emerged in coronary heart disease. In this study, we analyzed fatty acids and ankle-brachial index (ABI) in a Japanese cohort.

Methods

Peripheral arterial disease (PAD) was diagnosed in 101 patients by ABI ≤0.90 and/or by angiography. Traditional cardiovascular risk factors and components of serum fatty acids were examined in all patients (mean age 73.2±0.9 years; 81 males), and compared with those in 373 age- and sex-matched control subjects with no evidence of PAD.

Results

The presence of PAD (mean ABI: 0.71±0.02) was independently associated with low levels of gamma-linolenic acid (GLA) (OR: 0.90; 95% CI: 0.85–0.96; P = 0.002), eicosapentaenoic acid∶arachidonic acid (EPA∶AA) ratio (OR: 0.38; 95% CI: 0.17–0.86; P = 0.021), and estimated glomerular filtration rate (OR: 0.97; 95% CI: 0.96–0.98; P<0.0001), and with a high hemoglobin A1c level (OR: 1.34; 95% CI: 1.06–1.69; P = 0.013). Individuals with lower levels of GLA (≤7.95 µg/mL) and a lower EPA∶AA ratio (≤0.55) had the lowest ABI (0.96±0.02, N = 90), while the highest ABI (1.12±0.01, N = 78) was observed in individuals with higher values of both GLA and EPA∶AA ratio (P<0.0001).

Conclusion

A low level of GLA and a low EPA∶AA ratio are independently associated with the presence of PAD. Specific fatty acid abnormalities and imbalances could lead to new strategies for risk stratification and prevention in PAD patients.     

ERAP1 genetic variations associated with HLA-B27 interaction and disease severity of syndesmophytes formation in Taiwanese ankylosing spondylitis

IntroductionAnkylosing spondylitis (AS) is a familial, heritable disease specified by syndesmophyte formation leading to an ankylosed spine. Endoplasmic reticulum aminopeptidase 1 (ERAP1) genetic variations have been widely proved to be associated with AS in several ethnic populations. The aim of this study was to investigate whether ERAP1 single nucleotide polymorphisms (SNPs) are associated with AS susceptibility and disease severity in Taiwanese.MethodsFour ERAP1 SNPs (rs27037, rs27980, rs27044 and rs30187) were genotyped in 797 Taiwanese AS patients and 1,150 healthy controls. Distributions of genotype and alleles were compared between AS patients and healthy controls, and among AS patients stratified by clinical parameters.ResultsThe SNP rs27037T allele appeared to be a risk factor for AS susceptibility (P = 5.5 × 10^-5, OR 1.30, 95% CI: 1.15 to 1.48; GT+TT vs. GG P = 9.3 × 10^-5, OR 1.49, 95% CI: 1.22 to 1.82). In addition, the coding SNP (cSNP) rs27044G allele (P = 1.5 × 10^-4, OR 1.28, 95% CI: 1.13 to 1.46; CG+GG vs. CC, P = 1.7 × 10^-3, OR 1.44, 95% CI: 1.15 to 1.81) and the cSNP rs30187T allele (P = 1.7 × 10^-3, OR 1.23, 95% CI: 1.08 to 1.40; CT+TT vs. CC P = 6.1 × 10^-3, OR 1.38, 95% CI: 1.10 to 1.74) were predisposing factors for AS. Notably, the rs27044G allele carriers (CG+GG vs. CC, P = 0.015, OR 1.59, 95% CI: 1.33 to 2.30) and rs30187T allele carriers (CT+TT vs. CC, P = 0.011, OR 1.63, 95% CI: 1.12 to 2.38) were susceptible to syndesmophyte formation in AS patients. Furthermore, two cSNPs (rs27044 and rs30187) strongly associated with HLA-B27 positivity in AS patients. Finally, the ERAP1 SNP haplotype TCG (rs27037T/rs27980C/rs27044G) is a major risk factor for AS (adjusted P <0.00001, OR 1.38, 95% CI: 1.12 to 1.58) in Taiwanese.ConclusionsThis study provides the first evidence of ERAP1 SNPs involving syndesmophyte formation. The interactions between ERAP1 SNPs and HLA-B27 play critical roles in pMHC I pathway processing contributing to the pathogenesis of AS in multiple populations.     

Association of the Gene Polymorphisms IFN-γ +874, IL-13 ?1055 and IL-4 ?590 with Patterns of Reinfection with Schistosoma mansoni

Background

The immunologic findings that most consistently correlate with resistance in human schistosomiasis are high levels of IgE and low levels of IgG4. We have genotyped gene and promoter polymorphisms of cytokines associated with regulation of these isotypes in a cohort of men occupationally exposed to Schistosoma mansoni in western Kenya and evaluated their patterns with respect to resistance and susceptibility to reinfection after treatment and cure with praziquantel (PZQ).

Methodology/Principal Findings

In this cohort, polymorphisms in IL-4 (−590T high IgE), IL-13 (−1055T high producer) and IFN-γ (+874A high producer) demonstrated several correlations with resistance to reinfection. Resistance to reinfection was significantly correlated with the heterozygous IL-4 −590 genotype C/T (OR 3.5, [CI 1.2, 10.2]) compared to T/T. Among men with a homozygous IL-13 genotype CC/TT, having a T allele at the IFN-γ +874 position increased the odds of resistance relative to individuals with the IFN-γ +874 A/A genotype (OR = 17.5 [CI 3.0, 101.5]). Among men with homozygous A/A IFN-γ genotype, the heterozygous IL-13 genotype C/T was associated with resistance relative to the homozygous C/C or T/T genotypes (OR = 22.5 [CI 3.5, 144.4]). No increases in odds of resistance were found in relation to the IL-13 genotype among those with a T allele in the IFN-γ gene or in relation to the IFN-γ genotype among those with a heterozygous IL-13 genotype. Calculation of the attributable proportion of resistance showed a significant synergistic interaction between IL-13 −1055 C/T and IL-4 −590 C/T.

Conclusions

The identified polymorphisms do not by themselves confer resistance or susceptibility, but we propose that these genotypes allow the resistant phenotype to be developed and expressed upon suitable immune exposure. Based on the literature, these polymorphisms contribute to the regulation of their respective cytokines, likely leading to downstream differences in the production and interrelationships of critical defense mechanisms.     

Genetic Polymorphisms of Interleukin-16 and Risk of Knee Osteoarthritis

BackgroundInterleukin-16 (IL-16), a pleiotropic cytokine, plays a fundamental role in inflammatory diseases. This study investigates the association between IL-16 polymorphisms and the risk of knee osteoarthritis (OA) in a Chinese population.MethodsThe IL-16 rs11556218, rs4072111, and rs4778889 polymorphisms were determined in 150 knee OA cases and 147 healthy controls through polymerase chain reaction-restriction fragment length polymorphism.ResultsThe results suggested that the variants in IL-16 gene rs11556218 site were associated with a decreased knee OA risk after adjusting for age, sex, BMI, and smoking and drinking status (TG vs. TT: OR, 0.69; 95% CI, 0.53–0.89; P = 0.006; GG vs. TT: OR, 0.64; 95% CI, 0.45–0.90; P = 0.042; dominant model: OR, 0.68; 95% CI, 0.29–0.87; P = 0.002; G vs. T allele: OR, 0.77; 95% CI, 0.66–0.90; P = 0.003). Similarly, subjects bearing the rs4072111 variant genotypes and alleles also had a lower susceptibility to knee OA compared with those bearing the wild-type (CT vs. CC: OR, 0.66; 95% CI, 0.53–0.83; P = 0.002; TT vs. CC: OR, 0.57; 95% CI, 0.40–0.82; P = 0.027; dominant model: OR, 0.65; 95%, CI 0.52–0.80; P <0.001; T vs. C allele: OR, 0.69; 95% CI, 0.58–0.81; P <0.001). Further, the C allele and the combined genotype (CC+CT) of rs4778889 were associated with a slightly decreased risk of knee OA. In addition, we found two high-risk haplotypes: TTT (OR, 3.70) and GCC (OR, 6.22). Finally, serum IL-16 levels of knee OA patients were significantly higher than those of controls (P = 0.001).ConclusionsDespite the small sample size, this is the first study suggesting IL-16 gene polymorphisms to be associated with the risk of knee OA.     

Genetic Variations of IL-12B,IL-12Rβ1, IL-12Rβ2 in Behcet's Disease and VKH Syndrome

Purpose

To investigate the associations of single nucleotide polymorphisms (SNPs) of three genes (IL-12B, IL-12Rβ1 and IL-12Rβ2) in Behcet''s disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population.

Methods

A total of 806 BD cases, 820 VKH patients, and 1600 healthy controls were involved in this study. The first investigation included 400 BD patients, 400 VKH cases, and 600 healthy individuals. A second confirmatory study included a separate set of 406 BD patients, 420 VKH cases and another 1000 normal controls. Genotyping was carried out by PCR-restriction fragment length polymorphism assay and results were validated by using direct sequencing. The χ2 test was performed to compare the allele and genotype frequencies between cases and healthy controls.

Results

This study comprised two phases. In the first phase study, a significantly increased frequency of the rs3212227/IL-12B genotype CC and C allele was found in BD patients as compared to controls (Bonferroni corrected p value (p_c) = 0.009, OR 1.8; p_c = 0.024, OR 1.3, respectively). Moreover, the frequency of the C allele of rs3212227/IL-12B was also significantly increased in VKH patients (p_c = 0.012, OR 1.3, 95% CI 1.1 to 1.6). No associations were found for the other seven tested SNPs either in BD or VKH disease. The second study as well as the combined data confirmed the significant association of rs3212227/IL-12B with BD (CC genotype: combined p_c = 6.3×10⁻⁷, OR = 1.8; C allele: combined p_c = 2.0×10⁻⁵, OR = 1.3, respectively) and the C allele frequency of rs3212227/IL-12B as the risk factor to VKH patients (combined p_c = 2.5×10⁻⁵, OR 1.3, 95% CI 1.2 to 1.5).

Conclusions

Our study revealed that the IL-12B gene is involved both in the susceptibility to BD as well as VKH syndrome.     

A Meta-Analysis of the Association between ESR1 Genetic Variants and the Risk of Breast Cancer

BackgroundSingle nucleotide polymorphisms (SNPs) in the estrogen receptor gene (ESR1) play critical roles in breast cancer (BC) susceptibility. Genome-wide association studies have reported that SNPs in ESR1 are associated with BC susceptibility; however, the results of recent studies have been inconsistent. Therefore, we performed this meta-analysis to obtain more accurate and credible results.MethodsWe pooled published literature from PubMed, EMBASE, and Web of Science and calculated odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of associations using fixed effects models and random effects models. Twenty relevant case-control and cohort studies of the 3 related SNPs were identified.ResultsThree SNPs of the ESR1 gene, rs2077647:T>C, rs2228480:G>A and rs3798577:T>C, were not associated with increased BC risk in our overall meta-analysis. Stratified analysis by ethnicity showed that in Caucasians, the rs2228480 AA genotype was associated with a 26% decreased risk of BC compared with the GG genotype (OR = 0.740, 95% CI: 0.555–0.987). The C allele of the rs3798577:T>C variant was associated with decreased BC risk in Asians (OR = 0.828, 95% CI: 0.730–0.939), while Caucasians with this allele were found to experience significantly increased BC risk (OR = 1.551, 95% CI: 1.037–2.321). A non-significant association between rs2077647 and BC risk was identified in all of the evaluated ethnic populations.ConclusionRs3798577 was associated with an increased risk of BC in Caucasian populations but a decreased risk in Asians. Rs2228480 had a large protective effect in Caucasians, while rs2077647 was not associated with BC risk.     

Additive Effect between IL-13 Polymorphism and Cesarean Section Delivery/Prenatal Antibiotics Use on Atopic Dermatitis: A Birth Cohort Study (COCOA)

Background

Although cesarean delivery and prenatal exposure to antibiotics are likely to affect the gut microbiome in infancy, their effect on the development of atopic dermatitis (AD) in infancy is unclear. The influence of individual genotypes on these relationships is also unclear. To evaluate with a prospective birth cohort study whether cesarean section, prenatal exposure to antibiotics, and susceptible genotypes act additively to promote the development of AD in infancy.

Methods

The Cohort for Childhood of Asthma and Allergic Diseases (COCOA) was selected from the general Korean population. A pediatric allergist assessed 412 infants for the presence of AD at 1 year of age. Their cord blood DNA was subjected to interleukin (IL)-13 (rs20541) and cluster-of-differentiation (CD)14 (rs2569190) genotype analysis.

Results

The combination of cesarean delivery and prenatal exposure to antibiotics associated significantly and positively with AD (adjusted odds ratio, 5.70; 95% CI, 1.19–27.3). The association between cesarean delivery and AD was significantly modified by parental history of allergic diseases or risk-associated IL-13 (rs20541) and CD14 (rs2569190) genotypes. There was a trend of interaction between IL-13 (rs20541) and delivery mode with respect to the subsequent risk of AD. (P for interaction = 0.039) Infants who were exposed prenatally to antibiotics and were born by cesarean delivery had a lower total microbiota diversity in stool samples at 6 months of age than the control group. As the number of these risk factors increased, the AD risk rose (trend p<0.05).

Conclusion

Cesarean delivery and prenatal antibiotic exposure may affect the gut microbiota, which may in turn influence the risk of AD in infants. These relationships may be shaped by the genetic predisposition.     

Protective Role of the Interleukin 33 rs3939286 Gene Polymorphism in the Development of Subclinical Atherosclerosis in Rheumatoid Arthritis Patients

Objectives

To determine whether the interleukin-33 (IL-33)-interleukin-1 receptor like 1 (IL-1RL1) signaling pathway is implicated in the risk of subclinical atherosclerosis in patients with rheumatoid arthritis (RA).

Methods

A total of 576 Spanish RA patients from Northern Spain were genotyped for 6 well-known IL33-IL1RL1 polymorphisms (IL33 rs3939286, IL33 rs7025417, IL33 rs7044343, IL1RL1 rs2058660, IL1RL1 rs2310173 and IL1RL1 rs13015714) by TaqMan genotyping assay. The presence of subclinical atherosclerosis was determined by the assessment of carotid intima-media thickness (cIMT) by carotid ultrasound (US).

Results

RA patients carrying the TT genotype of the IL33 rs3939286 polymorphism had lower cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.71 ± 0.14 mm versus 0.76 ± 0.16 mm, respectively) while patients carrying the CT genotype had intermediate cIMT values (mean ± SD: 0.73 ± 0.17 mm). Moreover, RA patients carrying the mutant allele T of the IL33 rs3939286 polymorphism exhibited significantly lower cIMT values than those carrying the wild allele C (mean ± SD: 0.72 ± 0.16 mm versus 0.75 ± 0.18 mm respectively; p = 0.04). The association of both genotype and allele frequencies of IL33 rs3939286 and cIMT levels remained statistically significant after adjustment for sex, age at the time of US study, follow-up and center (p = 0.006 and p = 0.0023, respectively), evidencing that the potential effect conferred by IL33 rs3939286 may be independent of confounder factors. No association with other IL33-IL1RL1 genetic variants was observed.

Conclusions

In conclusion, our results may suggest a potential protective effect of the IL33 rs3939286 allele T in the risk of subclinical atherosclerosis in patients with RA.     

Prevalence of Cognitive Impairment in Recently Diagnosed Type 2 Diabetes Patients: Are Chronic Inflammatory Diseases Responsible for Cognitive Decline?

ObjectiveTo estimate the prevalence of cognitive impairment (CI) among patients recently diagnosed with type 2 diabetes (RDD) and to identify any relationships between CI and RDD comorbidities. Methods: One thousand seven hundred twelve patients with RDD participated in a cross-sectional study. The patients’ sociodemographic and clinical data were registered.ResultsThe sample population had an average age of 51 ± 11 years, and 63.26% of the patients were female. CI was diagnosed in 38 patients (2.2%) and was more common among both females (2.8% vs. 1.3%, p = 0.063) and the elderly (0% at an age ≤ 30 years vs. 10.4% at an age > 70 years, p = 0.0001). Rheumatoid arthritis (present in 15.8% vs. absent in 2.1%) and asthma (13% vs. 2.1%) correlated significantly with CI based on the results of our logistic regression analysis.ConclusionAge, female gender, rheumatoid arthritis and asthma are risk factors for CI in the setting of RDD.     

Two Susceptibility Loci to Takayasu Arteritis Reveal a Synergistic Role of the IL12B and HLA-B Regions in a Japanese Population

Takayasu arteritis (TAK) is an autoimmune systemic vasculitis of unknown etiology. Although previous studies have revealed that HLA-B^∗52:01 has an effect on TAK susceptibility, no other genetic determinants have been established so far. Here, we performed genome scanning of 167 TAK cases and 663 healthy controls via Illumina Infinium Human Exome BeadChip arrays, followed by a replication study consisting of 212 TAK cases and 1,322 controls. As a result, we found that the IL12B region on chromosome 5 (rs6871626, overall p = 1.7 × 10⁻¹³, OR = 1.75, 95% CI 1.42–2.16) and the MLX region on chromosome 17 (rs665268, overall p = 5.2 × 10⁻⁷, OR = 1.50, 95% CI 1.28–1.76) as well as the HLA-B region (rs9263739, a proxy of HLA-B^∗52:01, overall p = 2.8 × 10⁻²¹, OR = 2.44, 95% CI 2.03–2.93) exhibited significant associations. A significant synergistic effect of rs6871626 and rs9263739 was found with a relative excess risk of 3.45, attributable proportion of 0.58, and synergy index of 3.24 (p ≤ 0.00028) in addition to a suggestive synergistic effect between rs665268 and rs926379 (p ≤ 0.027). We also found that rs6871626 showed a significant association with clinical manifestations of TAK, including increased risk and severity of aortic regurgitation, a representative severe complication of TAK. Detection of these susceptibility loci will provide new insights to the basic mechanisms of TAK pathogenesis. Our findings indicate that IL12B plays a fundamental role on the pathophysiology of TAK in combination with HLA-B^∗52:01 and that common autoimmune mechanisms underlie the pathology of TAK and other autoimmune disorders such as psoriasis and inflammatory bowel diseases in which IL12B is involved as a genetic predisposing factor.     

The Effects of Genetic Variation in FTO rs9939609 on Obesity and Dietary Preferences in Chinese Han Children and Adolescents

The association of the rs9939609 single nucleotide polymorphism in FTO gene with obesity has been extensively investigated in studies of populations of European, African, and Asian ancestry. However, inconsistent results have been reported in Asian populations, and the relationship of FTO variation and dietary behaviors has only rarely been examined in Chinese children and adolescents. The aim of this study was to assess the association of rs9939609 with obesity and dietary preferences in childhood in a Chinese population. Epidemiological data including dietary preferences were collected in interviews using survey questionnaires, and rs9939609 genotype was determined by real-time PCR. The associations of rs9939609 genotypes with obesity and dietary preferences were analyzed by multivariate logistic regression using both additive and dominant models. The results showed that subjects with a TA or AA genotype had an increased risk of obesity compared with the TT participants; the odds ratios (ORs) were 1.47 (95% CI: 1.25–1.71, P = 1.73×10⁻⁶), and 3.32 (95% CI: 2.01–5.47, P = 2.68×10⁻⁶), respectively. After adjusting for age and gender, body mass index, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triglycerides, and low-density lipoprotein cholesterol were higher, and high-density lipoprotein cholesterol was lower in TA and AA participants than in those with the TT genotype. After additionally controlling for body mass index, the association remained significant only for systolic blood pressure (P = 0.005). Compared with TT participants, those with the AA genotype were more likely to prefer a meat-based diet (OR = 2.81, 95% CI: 1.52–5.21). The combined OR for obesity in participants with TA/AA genotypes and preference for a meat-based diet was 4.04 (95% CI: 2.8–5.81) compared with the TT participants who preferred a plant-based diet. These findings indicate the genetic variation of rs9939609 is associated with obesity and dietary preferences in Chinese children and adolescents.     

CARD9 gene rs4077515 polymorphism is associated with the susceptibility of Hashimoto’s thyroiditis and the development of thyroid cancer

AmisHashimoto’s thyroiditis (HT) is the most common type of autoimmune thyroiditis and is a risk factor for the occurrence of thyroid papillary carcinoma (PTC). The study aimed to explore the distribution of CARD9 rs4077515 polymorphism in HT and PTC patients, in order to evaluate its association with the occurrence and development of HT.Methods150 HT patients and 120 PTC cases were included. Genotypes of CARD9 rs40775155 polymorphism were sequenced and counted.ResultsA remarkable increase trend of rs4077515 AA genotype was found in HT cases in comparison with the control group, while GG genotype frequency exhibited a down trend. An excess of A allele was also detected in HT group. HT cases carrying AG and AA genotypes had high risk to receive hormonotherapy and needed a much larger dose. In comparison with HT cases, both AG and AA appeared more frequently in PTC patients, and are associated with the tumor size, LN metastasis and surgical margin. The AG (OR = 2.566, 95 % CI = 1.376–4.786) and AA (OR = 3.040, 95 % CI = 1.525–6.060) genotype carriers had a greater risk of developing PTC. The A allele of rs4077515 polymorphism was a risk allele for the onset of PTC among HT cases (OR = 1.775, 95 % CI = 1.260–2.502).ConclusionCARD9 rs4077515 polymorphism is likely to be a risk factor for HT in the Chinese Han population, it also contributes to the development of PTC for HT patients.     

血清白介素8基因多态性与食管鳞癌根治术后的相关性分析

摘要 目的：探讨与分析血清白细胞介素8（IL-8）基因多态性与食管鳞癌（ESCC）根治术后的相关性。方法：2017年8月到2020年6月选择在本院诊治的食管鳞癌患者98例作为研究对象,检测血清IL-8表达水平。所有患者都给予根治手术治疗,随访患者的预后并进行相关性分析。结果：所有患者术后随访到2021年7月,平均随访时间为25.69±2.58个月,死亡28例,死亡率为28.6 %（死亡组）。两组血清IL-8表达水平表达具有差异（P<0.05）。所有患者的基因型频率均符合Hardy-Weinberg这一平衡法则,表明本文所选取的样本均具有群体代表性。IL-8基因启动子rs4073A/T的AA基因型较死亡组高,TT基因型较死亡组低,两组A、T等位基因频率分布对比有差异（P<0.05）。直线相关性分析显示：IL-8基因启动子rs4073A/T的AA基因型、A等位基因、血清IL-8表达水平与预后死亡率存在相关性（P<0.05）。多因素logistic回归分析显示：IL-8基因启动子rs4073A/T的AA基因型、A等位基因、血清IL-8表达水平为导致患者随访死亡的主要因素（OR=2.051,3.094,P<0.05）。结论：食管鳞癌根治术后患者依然存在一定的死亡率,患者死亡与血清IL-8基因多态性存在相关性,同时多伴随有IL-8的高表达。IL-8基因启动子rs4073A/T的AA基因型、A等位基因、血清IL-8表达水平为导致患者死亡的主要因素。     

IL13 gene polymorphisms modify the effect of exposure to tobacco smoke on persistent wheeze and asthma in childhood,a longitudinal study

Background

Tobacco smoke and genetic susceptibility are risk factors for asthma and wheezing. The aim of this study was to investigate whether there is a combined effect of interleukin-13 gene (IL13) polymorphisms and tobacco smoke on persistent childhood wheezing and asthma.

Methods

In the Isle of Wight birth cohort (UK, 1989–1999), five IL13 single nucleotide polymorphisms (SNPs): rs1800925 (-1112C/T), rs2066960, rs1295686, rs20541 (R130Q) and rs1295685 were genotyped. Parents were asked whether their children had wheezed in the last 12 months at ages 1, 2, 4 and 10 years. Children who reported wheeze in the first 4 years of life and also had wheezing at age 10 were classified as early-onset persistent wheeze phenotype; non-wheezers never wheezed up to age 10. Persistent asthma was defined as having a diagnosis of asthma both during the first four years of life and at age 10. Logistic regression methods were used to analyze data on 791 children with complete information. Potential confounders were gender, birth weight, duration of breast feeding, and household cat or dog present during pregnancy.

Results

Maternal smoking during pregnancy was associated with early-onset persistent wheeze (OR 2.93, p < 0.0001); polymorphisms in IL13 were not (OR 1.15, p = 0.60 for the common haplotype pair). However, the effect of maternal smoking during pregnancy was stronger in children with the common IL13 haplotype pair compared to those without it (OR 5.58 and OR 1.29, respectively; p for interaction = 0.014). Single SNP analysis revealed a similar statistical significance for rs20541 (p for interaction = 0.02). Comparable results were observed for persistent childhood asthma (p for interaction = 0.03).

Conclusion

This is the first report that shows a combined effect of in utero exposure to smoking and IL13 on asthma phenotypes in childhood. The results emphasize that genetic studies need to take environmental exposures into account, since they may explain contradictory findings.     

Distinct Role of CD86 Polymorphisms (rs1129055, rs17281995) in Risk of Cancer: Evidence from a Meta-Analysis

Background and Purpose

Previous studies concerning the role of CD86 polymorphisms (rs1129055 and rs17281995) in cancer fail to provide compelling evidence. The aim of this study was to investigate the role of common polymorphisms in the risk of cancer by meta-analysis.

Methods

By using the search terms Cluster of Differentiation 86/CD86/B7-2/polymorphism/polymorphisms/cancer, we searched PubMed, Embase, CNKI, and Wanfang and identified four studies for rs1129055 (2137 subjects) and rs17281995 (2856 subjects) respectively. Cancer risk was estimated by odds ratio (OR) and 95% confidence interval (95% CI).

Major Findings

Overall, we observed significant reduced risk of cancer in relation to rs1129055. Compared with the individuals with AA genotype, the individuals with GG genotype appeared to have 62% decreased risk to develop cancer (GG versus AA: OR, 0.62; 95% CI, 0.49–0.79; P_het., 0.996). Similar effects were indicated in the G versus A allele model and the GG versus GA+AA genetic model (OR, 0.83; 95% CI, 0.74–0.93; P_het., 0.987; OR, 0.63; 95% CI, 0.50–0.79; P_het., 0.973). In addition, we found genotypes of rs17281995 had a major effect on overall cancer risk (CC versus GG: OR, 2.38; 95% CI, 1.43–3.95; P_het., 0.433; C versus G: OR, 1.23; 95% CI, 1.06–1.43; P_het., 0.521; CC versus GC+GG: OR, 2.38; 95% CI, 1.45–3.93; P_het., 0.443). The association was also observed in Caucasians and colorectal cancer. No obvious publication bias was detected in this meta-analysis.

Conclusions

These data reveal that rs1129055 may have protective effects on cancer risk in Asians and that rs17281995 is likely to contribute to risk of cancer, particularly colorectal cancer in Caucasians.