Associations of CYP4A11 gene–gene and gene–smoking interactions with essential hypertension in the male eastern Chinese Han population

Objectives: The aim of this study was to investigate the impact of CYP4A11 single-nucleotide polymorphisms (SNP), additional gene–gene and gene–environment interactions on essential hypertension (EH) risk. Methods: A total of 1648 participants (788 males, 860 females), with a mean age of 56.1 ± 14.1 years old, were selected, including 820 EH patients and 828 normotension subjects. Logistic regression was performed to investigate association of SNPs within CYP4A11 gene with high DBP, high SBP and EH risk, and generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene–gene interaction and gene–smoking interaction. Results: Logistic regression analysis showed that EH risk was significantly higher in carriers of C allele of the rs1126742 polymorphism than those with TT genotype (TC+CC versus TT, adjusted OR (95%CI) = 1.56 (1.24–1.91). In addition, we also found that EH risk was also significantly higher in carriers of G allele of the rs3890011polymorphism than those with CC genotype (CG+ GG versus CC, adjusted OR (95%CI) = 1.31 (1.15–2.03). GMDR analysis indicated a potential gene–gene interaction between rs1126742 and rs3890011 and a gene–environment interaction between rs1126742 and smoking. We found that subjects with TC or CC of rs1126742 and CG or GG of rs3890011genotype have the highest EH risk, OR (95%CI) was 2.52 (1.28–3.57). Smokers with TC or CC of rs1126742 genotype have the highest EH risk, OR (95%CI) was 2.20 (1.28–3.40). Conclusions: Gene–gene interaction between rs1126742 and rs3890011 and gene–environment interaction between rs1126742 and smoking were associated with increased EH risk.     

Association of peroxisome proliferator-activated receptor delta and additional gene–smoking interaction on cardiovascular disease

Aims: To investigate the impact of peroxisome proliferator–activator receptor delta (PPARD) gene polymorphism and additional gene–smoking interaction on cardiovascular disease (CVD) risk based on this Chinese population. Methods: A total of 1048 subjects (617 males, 431 females) with a mean age of 52.9 ± 14.1 years old were selected, including 520 CVD patients and 528 normal control subjects. The logistic regression model was used to examine the association between three SNPs and CVD risk, odds ratio (OR), and 95% confident interval (95%CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to investigate the gene–smoking interaction. Results: Genotypes of variants in rs2016520 and rs9794 were associated with decreased CVD risk, and CVD risk was significantly lower in carriers of C allele of the rs2016520 polymorphism than those with the TT genotype (TC+CC versus TT), adjusted OR (95%CI) = 0.71 (0.56–0.86). In addition, we also found that CVD risk was also significantly lower in carriers of the G allele of the rs9794 polymorphism than those with the CC genotype (CG+ GG versus CC), adjusted OR (95%CI) = 0.69 (0.53–0.86). GMDR analysis suggested a potential gene–environment interaction between rs2016520 and smoking. Overall, the two-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 62.17%, and never smokers with TC or CC of the rs2016520 genotype have the lowest CVD risk, compared to smokers with TT of rs2016520, OR (95%CI) was 0.42 (0.23–0.66). Conclusions: The minor allele of rs2016520 and rs9794 in PPAR-δ and interaction between rs2016520 and non-smoking were associated with decreased risk of CVD.     

Association of adiponectin gene polymorphisms and additional gene-gene interaction with nonalcoholic fatty liver disease in the Chinese Han population

Purpose

To investigate the association between the single nucleotide polymorphisms (SNPs) of the adiponectin gene and nonalcoholic fatty liver disease (NAFLD) as well as the impact of the interaction of multiple SNPs on NAFLD risk, based on a Chinese population study.

Methods

A total of 612 subjects (411 male, 201 female) were selected, including 302 NAFLD patients and 310 controls. Three SNPs were selected for genotyping in the case-control study: rs266729, rs822393, and rs1501299. A logistic regression model was used to examine the interaction between the SNPs and NAFLD. The odds ratio (OR) and 95 % confidence interval (95 % CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the interaction among SNPs.

Results

Logistic analysis showed a significant association between genotypes of variants in rs266729 and rs822393 and increased NAFLD risk. The carriers of the homozygous mutant of two SNP polymorphisms revealed increased NAFLD risk compared to those with wild-type homozygotes; ORs (95 % CI) were 1.31 (1.14–1.81) (p = 0.001) and 1.18 (1.05–1.71) (p = 0.005), respectively. There was a significant two-locus model (p = 0.0010) involving rs266729 and rs822393, indicating a potential gene-gene interaction between rs266729 and rs822393. Overall, the two-locus models had a cross-validation consistency of 10 and testing accuracy of 62.17 %. Subjects with the CG or GG and CT or TT genotype have the highest NAFLD risk compared to subjects with the CC-CC genotype; the OR (95 % CI) was 2.52 (1.31–3.82), p < 0.001, after covariate adjustment.

Conclusions

Our results support an important association of the rs266729 (?11377 G/C) and rs822393 (?4522 C/T) polymorphism with increased risk of NAFLD. The interaction analysis showed a combined effect of rs266729 and rs822393 on NAFLD.

     

The Drosha rs10719 T>C polymorphism is associated with preeclampsia susceptibility

Purpose: Drosha is a member of the micro RNA (miRNA) processing machinery that affects miRNA processing. Single-nucleotide polymorphisms (SNPs) in the Drosha gene might affect microRNA processing and the expression of various genes. The aim of this study is to investigate the association between SNPs in the Drosha gene and preeclampsia (PE) in the southeast of Iran. Methods: Genotyping of Drosha rs10719 and rs6877842 was performed using blood samples from 219 PE women and 205 healthy control subjects by a polymerase chain reaction-restriction fragment length polymorphism method. Results: The Drosha rs10719TC genotype was significantly associated with 1.6-fold higher risk of PE (odds ratio (OR, 1.6 [95% CI, 1.1–2.4], P = 0.026). In addition, the frequency of the Drosha rs10719CC genotype was significantly higher in PE women and was associated with threefold higher risk of PE (OR 3 [95% CI 1.4–6.3], P = 0.004). There was no association between the Drosha rs6877842 polymorphism and PE susceptibility. The CC–GG combined genotype was associated with 3.4-fold higher risk of PE (OR 3.4 [95% CI 1.4–8.1], P = 0.007). The haplotype-based association analysis showed higher frequency of C–G haplotype of Drosha rs10719 and rs6877842 polymorphisms with the increased risk of PE 1.5-fold (OR 1.5 [95% CI 1.1 – 2], P = 0.01). Conclusions: The Drosha rs10719TC and CC genotypes were associated with PE risk. The CC–GG combined genotype and C–G haplotype of Drosha rs10719 and rs6877842 polymorphisms may increase PE susceptibility.     

Gene–gene interaction between CD40 and CD226 gene on systemic lupus erythematosus in the Chinese Han population

The aim of the study is to investigate the impact of CD40 and CD226 gene single-nucleotide polymorphism (SNP) and additional gene–gene interaction on systemic lupus erythematosus (SLE) risk in Chinese Han populations. Three SNPs were selected for genotyping in the case–control study: rs4810485, rs763361, and rs3765456. Logistic regression was performed to investigate association between SNP within CD40 and CD226 and SLE. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the interaction among three SNPs. Logistic regression analysis showed that SLE risk was significantly higher in carriers of T allele of rs4810485 in CD40 gene than those with GG genotype (GT+ TT vs GG), adjusted OR (95 % CI) 1.84 (1.40–2.29). In addition, we also found SLE risk was also significantly higher in carriers of rs763361 T allele within CD226 gene than those with CC genotype (CT+ TT vs CC), adjusted OR (95 % CI) 1.89 (1.38–2.13). GMDR analysis suggested a potential gene–gene interaction between rs4810485 and rs763361. Overall, cross-validation consistency of the two-locus model was 10/10, and the testing accuracy was 62.17 %. We also found that subjects with GT or TT of rs4810485 and CT or TT of rs763361 genotype have the highest SLE risk, compared with subjects with GG of rs4810485 and CC of rs763361 genotype, and OR (95 % CI) was 2.14 (1.67–3.08), after covariates adjustment. Our results support an important association of rs4810485 in CD40 gene and rs763361 in CD226 gene polymorphism, combined effect of rs4810485 and rs763361 with increased risk of SLE.     

IL-17 polymorphisms and asthma risk: a meta-analysis of 11 single nucleotide polymorphisms

Objective: There has been significant interest in the association between asthma and the polymorphisms of IL-17A and IL-17F for a period of time. This work aims to present a clearer relationship between asthma and the polymorphisms of IL-17A and IL-17F. Method: Searches were performed in Medline, EMBASE, and the Chinese National Knowledge Infrastructure (CNKI) databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relationship between polymorphisms of IL-17A and IL-17F and asthma. Results: Nine studies comprising 3650 asthmatics and 3370 controls were included in this meta-analysis for all single nucleotide polymorphisms (SNPs) (2–6 per SNP). Our study examined the polymorphisms of IL-17F rs1889570 (C/T) (CC versus TT: OR?=?0.55, 95%CI?=?0.41–0.75; CT versus TT: OR?=?0.54, 95%CI?=?0.40–0.72; CC/CT versus TT: OR?=?0.55, 95%CI?=?0.42–0.72; CC versus CT/TT, OR?=?1.83, 95%CI?=?1.39–2.41), IL-17A rs4711998(A/G) (AA/AG versus GG: OR?=?0.67, 95%CI?=?0.46–0.98), and IL-17A rs3819024(A/G) (AA versus GG: OR?=?1.77, 95%CI?=?1.39–2.25) and found they were significantly related to the risk of asthma. Conclusion: Our systematic review showed that IL-17F rs1889570(C/T), IL-17A rs4711998(A/G) and IL-17A rs3819024(A/G) may be potential risk factors for asthma susceptibility.     

Impact of interaction between CYP1A1 genetic polymorphisms and smoking on coronary artery disease in the Han of China

Aims: To investigate the association of CYP1A1 genotype and additional gene–smoking interaction with coronary artery disease (CAD) risk based on a Chinese case-control study. Methods: A total of 1862 participants (1134 men, 728 women) were selected, including 620 CAD patients and 1242 normal controls. Logistic regression was performed to investigate association of CYP1A1 genotype, gene–gene, and gene–smoking interaction with CAD. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best gene–gene and gene–smoking interaction combination, cross-validation consistency, the testing balanced accuracy, and the sign test, to assess if each selected interaction was calculated. Results: The carriers of homozygous mutant of rs4886605 polymorphism and heterozygous of rs4646903 are associated with increased CAD risk than those with wild-type homozygotes; OR (95% CI) was 1.98 (1.53–2.61) and 1.58 (1.24–1.96), respectively. The carriers of homozygous mutant of rs1048943 polymorphism is associated with decreased CAD risk than those with wild-type homozygotes, OR (95% CI) = 0.75 (0.60–0.93). GMDR model indicated a potential gene–gene interaction between rs4886605 and rs4646903 and a potential gene–smoking interaction between rs4886605 and smoking. Participants with rs4886605-CT or TT and rs4646903-TC or CC genotype have the highest CAD risk, compared to participants with rs4886605-CC and rs4646903-TT genotype; OR (95% CI) was 2.72 (2.03–3.61). In addition, we also found that smokers with rs4886605-CT or TT genotype have the highest CAD risk, compared to nonsmokers with rs4886605-CC genotype; OR (95% CI) was 3.07 (2.23–3.96). Conclusions: rs4886605 and rs4646903 are associated with increased CAD risk, but rs1048943 is associated with decreased CAD risk; we also found gene–gene interaction between rs4886605 and rs4646903 and gene–environment interaction between rs4886605 and smoking.     

Polymorphisms of the IL-23R gene are associated with primary immune thrombocytopenia but not with the clinical outcome of pulsed high-dose dexamethasone therapy

Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder that is characterized by decreased platelet count. The interleukin-23 receptor (IL-23R) has been identified as a susceptibility gene for the development of multiple autoimmune diseases. To investigate the possible association of IL-23R gene single-nucleotide polymorphisms (SNPs) with ITP and the association with the clinical outcome of pulsed high-dose dexamethasone (HD-DXM) therapy, four SNPs in the IL-23R gene, rs10889677, rs1884444, rs7517847, and rs11209032, were tested in a cohort of 75 ITP subjects and 81 controls by direct sequencing. IL-23R rs1884444 GT/TT variant genotypes were observed to be associated with significantly increased risk of ITP as compared with controls (GT/TT vs. GG: odds ratio (OR) 2.776, 95 % confidence intervals (CI) 1.086–7.090, p?=?0.028). However, other three SNPs revealed no statistically significant differences between patients and controls (rs10889677 CA/AA vs. CC: OR 2.200, 95 % CI 0.727–6.661, p?=?0.155; rs11209032 GA/AA vs. GG: OR 0.747, 95 % CI 0.379–1.472, p?=?0.399; rs7517847 TG/GG vs. TT: OR 1.031, 95 % CI 0.544–1.956, p?=?0.925). Furthermore, IL-23R SNPs revealed no association with clinical outcome of HD-DXM therapy. This study suggests that polymorphism in the IL-23R gene, rs1884444, indicates a significant association with susceptibility to ITP in a recessive genetic model but does not have association with the clinical outcome of HD-DXM therapy.     

中国2型糖尿病人群AMPKα2基因多态性与冠心病风险的相关性研究

目的研究我国T2DM人群AMPKα2基因多态性与冠心病（CAD）风险的相关性。方法以326例T2DM患者为研究对象,其中180例伴有CAD（cAD＋组）,146例不伴CAD（CAD-组）。应用聚合酶链式反应-限制性内切酶片断长度多态性（PCR-RFLP）技术或基因测序方法,研究AMPKα2基因8个单倍型标记单核苷酸多态性（tag-SNPs）与CAD风险的关系。结果（1）SNP rs11206887 GG基因型携带者较非携带者发生CAD的风险显著增加（OR=2．507,95％CI=1．244-5．053,P=0．010）,校正年龄、性别、BMI、吸烟、糖尿病病程后仍存在统计学差异（OR′=2．469,95％CI′=1．182～5．157,P′=0．016）。（2）SNP rs2143749 GG基因型携带者较非携带者发生CAD的风险增高（OR=1．680,95％CI=1．029-2．741,P=0．038）。（3）SNP rs2746347 TT基因型携带者较非携带者发生CAD的风险有增高趋势（OR=2．875,95％CI=1．034-7．996,P=0．043,校正OR′=1．715,95％CI′=1．016-2．895,P′=0．044）。（4）SNPrs2143749和SNP rs11206887 GG／GG基因型组合携带者较非携带者发生CAD的风险增高（P=0．014）。结论我国T2DM患者AMPK α2 SNPs与CAD的发病风险可能相关。     

Association between genetic variants in pre-miRNA and colorectal cancer risk in a Chinese population

Introduction

Single-nucleotide polymorphisms (SNPs) in pre-miRNAs may alter microRNA expression levels or processing and then contribute to the susceptibility of cancer development. We hypothesized that SNPs in pre-miRNAs may be associated with the risk of colorectal cancer (CRC).

Materials and methods

We genotyped four common polymorphisms (i.e., rs11614913, rs3746444, rs2910164, and rs2292832) in pre-miRNAs of 353 CRC patients and 540 healthy controls to investigate the association between the SNPs and the risk of CRC using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay.

Results

The rs11614913 CT, TT genotypes, and T allele were associated with an increased risk of CRC compared with the CC genotype and C allele (CT vs. CC: OR = 7.34, 95 % CI 3.76–14.34; TT vs. CC: OR = 13.66, 95 % CI 6.76–27.6; T vs. C: OR = 1.99, 95 % CI 1.63–2.42, respectively). Interestingly, using the rs2910164 GG genotype as a reference, the rs2910164 GC genotype was associated with an increased risk of CRC (OR = 1.49, 95 % CI 1.02–2.18), whereas the rs2910164 CC genotype was associated with a decreased risk of CRC (OR = 0.58, 95 % CI 0.37–0.93). When compared with the rs2910164G allele, rs2910164 C allele was associated with a reduced risk of CRC (OR = 0.80, 95 % CI 0.66–0.97, p = 0.02).

Conclusion

These findings suggest that rs11614913 and rs2910164 polymorphisms may be associated with the etiology of CRC.     

Association of AdipoQ single-nucleotide polymorphisms and smoking interaction with the risk of coronary heart disease in Chinese Han population

Aims: To investigate the impact of AdipoQ polymorphisms, and their additional interactions with smoking and drinking on coronary heart disease (CHD) risk based on Chinese population. Methods: Hardy?Weinberg equilibrium (HWE) was performed using SNPStats (available online at http://bioinfo.iconcologia.net/SNPstats). Generalized multifactor dimensionality reduction (GMDR) model was used to screen the best gene?gene and gene?environment interaction combinations. Logistic regression was performed to investigate association between four single-nucleotide polymorphisms (SNPs) and CHD and the interaction effect between rs1501299 and smoking. Results: Logistic analysis showed that CHD risks were higher in carriers with homozygous mutant of rs1501299 and rs2241766 than those with wild-type homozygotes, odds ratio (ORs) (95%CI) were 1.49 (1.19–1.95) and 1.71 (1.33–2.24), respectively, but CHD risks were lower in carriers with homozygous mutant of rs7649121 than those with wild-type homozygotes, OR (95%CI) was 0.72 (0.51–0.96). GMDR model indicated that there was a significant two-locus model (p = 0.0107) involving rs1501299 and current smoking, indicating a potential gene–environment interaction between rs1501299 and current smoking. Overall, the cross-validation consistency of this model was 9/10, and the testing accuracy was 60.11% (p = 0.0010). T-allele carriage had 42% prevalence, and one-quarter of them were current smokers. Smokers with rs1501299-GT or TT genotype have the highest CHD risk, compared to never-smokers with rs1501299-GG genotype, OR (95%CI) was 3.56 (1.91–5.42), after adjustment for gender, age, alcohol status, and body mass index. But we did not find any significant gene–gene and gene–drinking interaction combinations in GMDR models. Conclusions: Polymorphisms in rs1501299 and rs2241766, and their additional interactions between rs1501299 and smoking were associated with increased CHD risks: polymorphism in rs7649121 was associated with decreased CHD risks.     

Adiponectin receptor 1 and small ubiquitin-like modifier 4 polymorphisms are associated with risk of coronary artery disease without diabetes

Background The genes encoding adiponectin receptor 1 (ADIPOR1) and small ubiquitin-like modifier 4 (SUMO4) have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two genes, acting separately or interacting, affect risk of coronary artery disease (CAD) without diabetes. Methods We genotyped 200 CAD patients without diabetes and 200 controls without CAD or diabetes at three single-nucleotide polymorphisms (SNPs) in ADIPOR1 and one SNP in SUMO4, which were chosen based on previous studies. Potential associations were also explored between these SNPs and clinical characteristics of CAD without diabetes. Results Risk alleles at three SNPs in ADIPOR1 (rs7539542-G, rs7514221-C and rs3737884-G) and the G allele at SNP rs237025 in SUMO4 significantly increased risk of CAD without diabetes, with ORs ranging from 1.79 to 4.44. Carriers of any of these four risk alleles showed similar adverse clinical characteristics. Compared with individuals with a CC or GC genotype, those with a GG genotype at rs3737884 were at significantly higher risk of CAD that affected the left anterior descending coronary artery (OR: 6.77, P = 0.009), the right coronary artery (OR: 4.81, P = 0.028) or a relatively large number of vessels (P = 0.04). Individuals carrying a risk allele at one or more of the three SNPs in ADIPOR1 as well as a risk allele at the SNP in SUMO4 were at significantly higher risk of CAD without diabetes than individuals not carrying any risk alleles (OR: 5.82, 95% CI: 1.23?27.7, P = 0.013). Conclusions SNPs in ADIPOR1 and SUMO4 are associated with elevated risk of CAD without diabetes, and SNPs in the two genes may interact to jointly affect disease risk.     

Effects of interactions between environmental factors and KIF1B genetic variants on the risk of hepatocellular carcinoma in a Chinese cohort

AIM: To examine the effect of the potential interaction between KIF1B variants (rs17401966 and rs3748578) and environmental factors on the risk of hepatocellular carcinoma (HCC) in a high-risk region in China.METHODS: Three hundred and six patients with HCC and 306 hospital-based control participants residing in the Shunde region of Guangdong Province, China were enrolled. Clinical characteristics were collected by reviewing the complete medical histories from the patient archives, and epidemiological data were collected using a questionnaire and clinical examination. Two single nucleotide polymorphisms (SNPs) of KIF1B (rs17401966 and rs3748578) were chosen for the current study. All subjects were genotyped using a TaqMan real-time polymerase chain reaction. Multiplicative and additive logistic regression models were used to evaluate various gene-environment interactions.RESULTS: Smoking, frequent consumption of raw freshwater fish, hepatitis B virus (HBV) infection, and a family history of HCC were important risk factors for HCC in this population. Chronic infection with HBV was the most important environmental risk factor for HCC [odds ratio (OR) = 12.02; 95% confidence interval (95%CI): 6.02-24.00]. No significant association was found between the KIF1B variants alone and the risk of HCC. Nevertheless, a significant additive effect modification was observed between rs17401966 and alcohol consumption (P for additive interaction = 0.0382). Compared with non-drinkers carrying either the AG or GG genotype of rs17401966, individuals classified as alcohol consumers with the AA genotype of rs17401966 had a significantly increased risk of HCC (OR = 2.36; 95%CI: 1.49-3.74).CONCLUSION: The gene-environment interaction between the KIF1B rs17401966 variant and alcohol consumption may contribute to the development of HCC in Chinese individuals.     

Genetic variant of <Emphasis Type="BoldItalic">IL-10RA</Emphasis> and susceptibility to rheumatoid arthritis in a Chinese population

The aim of this study was to investigate the relationship between the single-nucleotide polymorphisms (SNPs) of interleukin 10 alpha receptor (IL10RA) gene and rheumatoid arthritis (RA) in a Chinese population. We examined 533 RA patients and 958 subjects as a control group. Three IL-10RA SNPs (rs9610, rs2229113 and rs3135932) were genotyped using TaqMan genotyping assays on Fluidigm 192.24 system. The IL-10RA rs9610 A allele was increased in patient group compared with control subjects (OR = 1.232, 95 % CI = 1.052–1.442, p = 0.030). Significant difference in genotype distribution was found in RA patients and controls (χ2 = 15.32, p < 0.001). We also discovered a statistical significance under the dominant model (GG + AG versus AA: OR = 0.676, 95 % CI = 0.546–0.837, p < 0.001). However, no significant difference was discovered in the recessive model (GG versus AG + AA: OR = 1.013, 95 % CI = 0.754–1.361, p = 0.932). Interestingly, significant differences were detected both in the allele and genotype frequencies of rs9610 between anti-CCP positive patients and anti-CCP negative patients (χ2 = 7.209, p = 0.007; χ2 = 9.061, p = 0.011; respectively). We also found a significant difference in genotype frequency at rs9610 in females compared with males (χ2 = 7.658, p = 0.022). Unfortunately, we failed to find any significant results between two IL-10RA SNPs (rs2229113 and rs3135932) and RA susceptibility. The findings suggest that IL-10RA rs9610 polymorphism might contribute to RA susceptibility.     

Relationship between interleukin-6 polymorphism and susceptibility to chronic hepatitis B virus infection

AIM:To identify the relationship between tag single nucleotide polymorphisms(tag SNPs) of interleukin-6(IL-6) gene and susceptibility to chronic hepatitis B virus(HBV) infection in a Han Chinese population.METHODS:We performed a case-control study of501 Chinese patients with chronic HBV infection and301 self-limiting HBV-infected individuals as controls.Genomic DNA was isolated from the whole blood of all subjects using phenol/chloroform with MaXtract highdensity tubes. Tag SNPs were identified using genotype data from the panel(Han Chinese in Beijing) of the phase II HapMap Project. Four tag SNPs in IL-6(rs17147230A/T,rs2066992G/T,rs2069837A/G and rs2069852A/G) were genotyped by the Multiplex Snapshot technique. The genotype and allele frequencies were calculated and analyzed.RESULTS:Five haplotypes were involved in the analysis,with frequencies higher than 0.03. One of the haplotypes,TTAA,was significantly different between the two groups. Overall haplotype P values were:ATAA,P = 0.605,OR(95%CI) = 1.056(0.860-1.297); TGAG,P = 0.385,OR(95%CI) = 1.179(0.813-1.709); TGGG,P = 0.549,OR(95%CI) = 1.087(0.827-1.429); TTAA,P = 0.004,OR(95%CI) = 0.655(0.491-0.873); TTAG,P = 0.266,OR(95%CI) = 1.272(0.832-1.944). However,the four SNPs showed no significant genotype/allele associations with susceptibility to chronic HBV infection. Overall allele P values were:rs17147230,P = 0.696,OR(95%CI) = 1.041(0.850-1.276); rs2066992,P = 0.460,OR(95%CI)= 1.090(0.868-1.369); rs2069837,P = 0.898,OR(95%CI) = 0.983(0.759-1.274); rs2069852,P = 0.165,OR(95%CI) = 0.859(0.693-1.064). Overall genotype P values were:rs17147230,P = 0.625; rs2066992,P= 0.500; rs2069837,P = 0.853; and rs2069852,P =0.380.CONCLUSION:The four tag SNPs of IL-6 gene may be associated with susceptibility to chronic HBV infection in the Han Chinese population.     

CD14 and IL6 polymorphisms are associated with a pro-atherogenic profile in young adults with acute myocardial infarction

This study investigated the relationship of polymorphisms in genes encoding CD14, IL-6 and TLR4 with metabolic, inflammatory and endothelial markers in young adults with acute myocardial infarction (AMI). Glucose, lipids, nitrate and inflammatory markers, flow mediated vasodilatation (FMV) and flow mediated by nitrate (FMN) were evaluated in 102 AMI and 108 non-AMI (control group) young individuals (<45 years). CD14 ?260C>T (rs2569190), IL6 ?174G>C (rs1800795) and TLR4 c.896A>G (rs4986790) and TLR4 c.1196C>T (rs4986791) polymorphisms were analyzed by PCR–RFLP. Minor allele frequencies of CD14, IL6 and TLR4 polymorphisms were similar between AMI and control groups (p > 0.05). In AMI group, individuals carrying IL6 ?174CC genotype had higher serum triglycerides, VLDL cholesterol and glucose compared to the IL6 ?174GG/GC genotype carriers (p < 0.05). Multiple logistic analysis showed that IL6 ?174CC genotype carriers had increased risk for hyperglycemia (>5.77 mmol/l) [OR: 6.75, 95 % CI: 1.80–24.40, p = 0.004] and hypertriglyceridemia (>2.68 mmol/l) [OR: 3.00, 95 % CI: 1.00–9.00, p = 0.043]. Moreover, CD14 ?260TT genotype was associated with reduced serum HDL cholesterol [OR: 3.10, 95 % CI: 1.00–9.01, p = 0.044] and apolipoprotein AI [OR: 3.20, 95 % CI: 1.00–9.70, p = 0.038] in AMI group. Relationship between CD14 and IL6 variants and altered inflammatory and endothelial (nitrate, FMV and FMN) markers was not found in both AMI and control groups. The IL6 ?174G>C and CD14 ?260C>T polymorphisms are likely to be associated with a pro-atherogenic profile but not with increased inflammatory markers and endothelial dysfunction in young AMI patients.     

Interaction between ALOX15 polymorphisms and coronary artery disease in North Indian population

Background: Coronary artery disease (CAD) is major cause of death and morbidity worldwide. Arachidonate 12/15-lipoxygenase (ALOX) is a member of the lipid peroxidizing enzyme family and implicated in the pathogenesis of atherosclerosis, but with contradicting results. Aim: The present study aimed to investigate the association of two polymorphisms in ALOX15 (rs2619112 and rs7217186) and the risk of CAD in North Indian population. Methods: A total of 500 angiographically confirmed CAD patients and 500 control subjects of North Indian population were recruited in the case-control study and genotyped by PCR-RFLP. Results: The data showed a significant association between the two polymorphisms and CAD. Multiple logistic regression revealed heterozygous genotype of both the polymorphisms viz. GA of rs2619112 and CT of rs7217186 to be associated with significant high risk of CAD after adjustment for confounders (p = 0.034, OR = 2.274, 95% CI (1.062–4.870) and p = 0.000, OR = 3.407, 95% CI (2.092–5.548) respectively). Stratified analysis based on gender showed GA and AA of rs2619112 each significantly increased the risk of CAD in females (p = 0.001, OR = 13.120, CI = 2.780–61.928; p = 0.028, OR = 5.393, CI = 1.196–24.316 respectively) whereas only GA increased CAD risk in males (p = 0.005, OR = 2.277, CI = 1.290–4.020). In case of rs7217186, CT and TT showed a significant high risk of CAD in males (p = 0.000, OR = 4.048, CI = 2.678–6.119; p = 0.000, OR = 2.861, CI = 1.928–4.245). Conclusion: The present study shows that rs7217186:C > T and rs2619112:G > A of ALOX15 are associated with increased risk of CAD in the North Indian population.     

Glutathione peroxidase 3 gene polymorphisms and the risk of sudden sensorineural hearing loss

The glutathione peroxidase 3 gene (GPX3) is reported to be a risk factor for arterial ischaemic stroke and cerebral venous thrombosis. GPX3 may be one of the aetiologies of sudden sensorineural hearing loss (SSNHL), which might be attributed to the genetic effect of GPX3 by influence reactive oxygen species (ROS). Unbalanced ROS have been associated with susceptibility to SSNHL. Therefore, we conducted a case–control study with 416 SSNHL cases and 255 controls. Five single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan genotyping assays. Each SNP was tested using the Hardy–Weinberg equilibrium (HWE), and the genetic effects were evaluated using three inheritance models. All five SNPs were in HWE. As the result, the AG genotype of rs3805435 had an adjusted odds ratio (OR) of 0.54 (95% confidence interval = 0.37–0.79, p = 0.001) compared with the AA genotype in the SSNHL cases. The GG and AG genotypes of the SNP rs3805435 were associated with SSNHL under the dominant model (p = 0.002, OR = 0.58). In conclusion, these results suggest that GPX3 polymorphisms influence susceptibility to SSNHL in southern Taiwan.     

Interleukin-1 gene cluster and IL-1 receptor polymorphisms in Iranian patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology with a complex pathogenesis involving multiple genetic and environmental contributions. Single-nucleotide polymorphisms (SNPs) in cytokine genes are associated with higher or lower cytokine activity, which can alter the susceptibility to certain diseases or their clinical outcomes. We investigated SNPs of the IL-1 family in Iranian SLE patients and normal individuals. We obtained blood samples from 207 SLE patients and 213 healthy controls. Cytokine genotyping was performed by polymerase chain reaction with sequence-specific primers. The following SNPs were assessed: IL-1A rs1800587, IL-1B rs16944 and rs1143634, IL-1R1 rs2234650 and IL-1RN rs315952. The frequency of the IL-1RN rs315952 CT genotype was significantly lower among patients with SLE compared with healthy controls (OR = 0.63, 95 % CI = 0.42–0.95; P < 0.05 relative to reference genotype and OR = 0.62, CI = 0.42–0.93; P < 0.05 relative to homozygous genotypes). For all other studied alleles and genotypes, there were no significant differences concerning genotype frequencies between patients and controls. A significant increase in IL-1RN rs315952 T allele frequency was noted in patients with a hematologic manifestation (OR = 1.75; 95 % CI = 1.07–2.84; P = 0.033). Polymorphism in IL-1RN rs315952 was significantly associated with SLE in Iranian patients, rs315952CT genotype being a protective factor. We found that IL-1RN rs315952 T allele frequency was significantly higher in patients with hematologic manifestations. Variation at this locus may affect IL-1 receptor antagonist activity, supporting the hypothesis that altered or imbalanced IL1 production may affect the risk of developing SLE.     

LBP and CD14 polymorphisms correlate with increased colorectal carcinoma risk in Han Chinese

AIM: To explore the associations of polymorphisms of lipopolysaccharide binding protein (LBP), cluster of differentiation 14 (CD14), toll-like receptor 4 (TLR-4), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) with the colorectal carcinoma (CRC) risk in Han Chinese. METHODS: Polymorphisms of LBP (rs1739654, rs223 2596, rs2232618), CD14 (rs77083413, rs4914), TLR-4 (rs5030719), IL-6 (rs13306435) and TNF-α (rs35131721) were genotyped in 479 cases of sporadic colorectal carcinoma and 486 healthy contr...