Genetic association of cyclooxygenase-2 gene polymorphisms with Parkinson’s disease susceptibility in Chinese Han population

Objective: The aim of this study was to explore the genetic association of cyclooxygenase-2 (COX2) gene promoter region polymorphisms with Parkinson’s disease (PD) susceptibility in Chinese Han population. Methods: The genotyping of COX2 gene polymorphisms was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 122 patients with PD and 120 healthy persons. The association strength of gene polymorphism with disease was measured by odds ratio (OR) and 95% confidence interval (95% CI) calculated using χ² test which also evaluated the Hardy-Weinberg equilibrium (HWE) of gene polymorphism in controls. The linkage disequilibrium and haplotype were also analyzed as evidence in the analysis of association. Results: On condition that the genotypes distributions of COX2 -1290A>G, -1195G>A, -765G>C in the control group all conformed to HWE, however, only the homozygous genotype AA of -1195G>A polymorphism showed an association with PD (OR=0.432, 95% CI=0.196-0.950). In addition, in haplotype analysis, G-A-C haplotype frequency in cases was significantly lower than the controls, compared with the common haplotype A-G-G (P=0.031, OR=0.375, 95% CI=0.149-0.940). Conclusions: COX2 -1195G>A polymorphism might play a protective role in the onset of PD and G-A-C haplotype in this three promoter region polymorphisms also showed a negative association.     

Correlation between the interactions of ABCA4 polymorphisms and smoking with the susceptibility to age-related macular degeneration

Objective: Our study was aimed to analyze the relationship between retina-specific ATP-binding cassette, sub-family A, member 4 (ABCA4) gene polymorphisms and gene-environment interactions with age-related macular degeneration (AMD) susceptibility. Methods: 98 AMD patients and 110 healthy controls, matched in age and sex, were enrolled in this study. ABCA4 polymorphisms (2633C>A, 5646G>A and 6389T>A) were determined by direct sequencing. Differences of genotype and allele distributions were analyzed by χ² test. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were adopted to represent the relative risk of AMD. Gene-environment interactions were analyzed using crossover analysis. Results: 2633C>A polymorphism had no obvious correlation with AMD risk. Genotype AA and allele A in 5646G>A polymorphism significantly increased the risk of AMD (OR=4.753, 95% CI=1.249-18.085; OR=1.944, 95% CI=1.209-3.126). 6389T>A polymorphism AA genotype had no significant correlation with AMD risk, but the A allele distinctly enhanced the AMD risk (OR=1.681, 95% CI=1.071-2.639). Afterwards, we analyzed the interactions between ABCA4 polymorphisms and smoking on AMD. Smoking had interactions with all of 2633C>A (CC+CA), 5646G>A and 6389T>A polymorphisms, and the interactions were significantly correlated with AMD. Conclusions: 2633C>A (CC+CA) genotype, 5646G>A and 6389T>A polymorphisms of ABCA4 gene and smoking are susceptible factors for AMD, and the interactions of ABCA4 polymorphisms with smoking increased the risk of AMD.     

Association between E-cadherin (CDH1) polymorphisms and pancreatic cancer risk in Han Chinese population

This study was designed to investigate the associations between E-cadherin (CDH1) gene polymorphisms and pancreatic cancer (PC) risk predisposition. We undertook a case-control study to analyze three E-cadherin polymorphisms (+54T>C, -160C>A and -347G→GA) in an Han Chinese population, by extraction of genomic DNA from the peripheral blood of 368 patients with PC and 376 control participants and performed E-cadherin genotyping using DNA sequencing. Overall, no statistically significant association was observed in +54T>C. Nevertheless, -347G→GA genotype was at increased risk of PC (P=0.022; odds ratio (OR) =1.128, CI 95%: 1.017-1.251). Furthermore, -347GA/GA genotype pancreatic cancers were more significantly common in cases of advanced T stage, lymph node metastasis and clinical pathological stage than G or G/GA genotypes PC. However, -160C>A genotype demonstrated a protective effect in PCs (P=0.017; OR=0.883, CI 95%: 0.798-0.977). In conclusion, polymorphism in -347G→GA was observed to be associated with susceptibility of PC. However, -160C>A polymorphism indicated to play a protective role in susceptibility to PC. Nevertheless, further investigation with a larger sample size is needed to support our results.     

Lack of association between polymorphisms of the DNA base excision repair genes MUTYH and hOGG1 and keratoconus in a Polish subpopulation

Introduction

Keratoconus (KC) is a non-inflammatory thinning of the cornea and a leading indication for corneal transplantation. Oxidative stress plays a role in the pathogenesis of this disease. The products of the hOGG1 and MUTYH genes play an important role in the repair of oxidatively modified DNA in the base excision repair pathway. We hypothesized that variability in these genes may change susceptibility to oxidative stress and predispose individuals to the development of KC. We investigated the possible association between the c.977C>G polymorphism of the hOGG1 gene (rs1052133) and the c.972G>C polymorphism of the MUTYH gene (rs3219489) and KC occurrence as well as the modulation of this association by some KC risk factors.

Material and methods

A total of 205 patients with KC and 220 controls were included in this study. The polymorphisms were genotyped with polymerase chain reaction (PCR) restriction fragment length polymorphism and PCR-confronting two-pair primer techniques. Differences in genotype and allele frequency distributions were evaluated using the χ² test, and KC risk was estimated with an unconditional multiple logistic regression with and without adjustment for co-occurrence of visual impairment, allergies, sex and family history for KC.

Results

We did not find any association between the genotypes and combined genotypes of the c.977C>G polymorphism of the hOGG1 gene and the c.972G>C polymorphism of the MUTYH gene and the occurrence of KC.

Conclusions

Our findings suggest that the c.977C>G-hOGG1 polymorphism and the c.972G>C-MUTYH polymorphism may not be linked with KC occurrence in this Polish subpopulation.     

Surfactant protein B gene polymorphisms is associated with risk of bronchopulmonary dysplasia in Chinese Han population

Objective: To investigate the relationship between Surfactant protein B (SP-B) gene polymorphisms and bronchopulmonary dysplasia (BPD) development in preterm infants of China Han ethnic population. Methods: SP-B gene polymorphisms were studied in 134 neonates who were born at < 32 weeks of gestation, with the diagnosis of BPD and in a control group of 168 preterm infants without BPD. Genotyping for SP-B was performed by polymerase chain reaction (PCR) and gene sequencing. Results: In this study, three of the SNP genotypes, -18C/A, 1580C/T and 4564T/C were common identified in SP-B gene. The -18C/A genotype was found to be significantly associated with BPD (χ² = 10.741, P < 0.01), with P < 0.01 for the dominant model (OR = 1.712, 95% CI = 1.228-2.3894) and the allelic model (OR = 1.787, 95% CI = 1.276-2.502). The 1580C/T genotype was found to be associated with BPD (χ² = 7.014, P < 0.05), with P < 0.05 for the dominant model (OR = 0.752, 95% CI = 0.593-0.954) and P < 0.01 for the allelic model (OR = 0.706, 95% CI = 0.548-0.909). The 4564T/C genotypes and alleles were found not to be associated with BPD (χ² = 3.399 and 3.227, P > 0.05). Conclusion: SP-B -18C/A and 1580C/T polymorphisms are associated with BPD. The 1580C/T polymorphism was protective while the -18C/A polymorphism increased the risk for BPD. SP-B 4564T/C polymorphism is not associated with BPD.     

Validation of rs2956540:G>C and rs3735520:G>A association with keratoconus in a population of European descent

Corneal ectasias, among which keratoconus (KC) is the single most common entity, are one of the most frequent reasons for corneal grafting in developed countries and a threatening complication of laser in situ keratomileusis. Genome-wide association studies have previously found lysyl oxidase (LOX) and hepatocyte growth factor (HGF) associated with susceptibility to KC development. The aim of our study was to validate the effects of seven single-nucleotide polymorphisms (SNPs) within LOX and HGF over KC. Unrelated Czech cases with KC of European descent (108 males and 57 females, 165 cases in total) and 193 population and gender-matched controls were genotyped using Kompetitive Allele Specific PCR assays. Fisher''s exact tests were used to assess the strength of associations. Evidence for association was found for both of the tested loci. It was strongest for rs3735520:G>A near HGF (allelic test odds ratio (OR)=1.45; 95% confidence interval (CI), 1.06–1.98; P=0.018) with A allele being a risk factor and rs2956540:G>C (OR=0.69; 95% CI, 0.50–0.96; P=0.024) within LOX with C allele having a protective effect. This first independent association validation of rs2956540:G>C and rs3735520:G>A suggests that these SNPs may serve as genetic risk markers for KC in individuals of European descent.     

Interleukin-17A gene polymorphism is associated with susceptibility to gastric cancer

We conducted a study to investigate the role of three common SNPs in the IL-17A and IL-17F genes (rs2275913G>A, rs3748067C>T and rs763780T>C) in the development of gastric cancer, and their interaction with H.pylori infection. A total of 326 patients with gastric cancer and 326 control subjects were consecutively recruited between May 2012 and May 2014. Genotyping of IL-17A rs2275913G>A and rs3748067C>T and IL-17F rs763780T>C was performed in a 384-well plate format on the Sequenom MassARRAY platform. By logistic regression analysis, individuals carrying the GA and AA genotypes of IL-17 rs2275913G>A were significantly associated with an increased risk of gastric cancer when compared with GG genotype, and the adjusted Ors (95% CI) were 1.46 (1.03-2.06) for GA genotype and 2.57 (1.51-4.43) for AA genotype. We observed that the GA+AA genotype of rs2275913 was associated with an increased risk of gastric cancer among H.pylori infection subjects (OR=2.21, 95% CI=1.29-3.79). In conclusion, we found that there was a significant association between L-17A rs2275913G>A polymorphism and increased gastric cancer risk, especially in H.pylori infection subjects.     

Association of MDR1 gene polymorphisms with the risk of hepatocellular carcinoma in the Chinese Han population

The multidrug resistance 1 gene (MDR1) is an important candidate gene for influencing susceptibility to hepatocellular carcinoma (HCC). The objective of the present study was to evaluate the association of MDR1 polymorphisms with the risk of HCC in the Chinese Han population. A total of 353 HCC patients and 335 healthy subjects were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), created restriction site-PCR (CRS-PCR) and DNA sequencing methods were used to identify MDR1 gene polymorphisms. Two allelic variants (c.335T>C and c.3073A>C) were detected. The CC genotype of the c.335T>C polymorphism was associated with an increased risk of developing HCC compared to the TT genotype (OR = 2.161, 95%CI = 1.350-3.459, χ² = 10.55, P = 0.0011). The risk of HCC was significantly higher for the CC genotype in the c.3073A>C polymorphism compared to the AA genotype in the studied populations (CC vs AA: OR = 2.575, 95%CI = 1.646-4.028, χ² = 17.64, P < 0.0001). The C allele of the c.335T>C and c.3073A>C variants may contribute to the risk of HCC (C vs T of c.335T>C: OR = 1.512, 95%CI = 1.208-1.893, χ² = 13.07, P = 0.0003, and C vs A of c.3073A>C: OR = 1.646, 95%CI = 1.322-2.049, χ² = 20.03, P < 0.0001). The c.335T>C and c.3073A>C polymorphisms of the MDR1 gene were associated with the risk of occurrence of HCC in the Chinese Han population. Further investigations are needed to confirm these results in larger different populations.     

Association of ERCC gene polymorphism with osteosarcoma risk

BackgroundThe relationship between ERCC gene polymorphism and osteosarcoma risk / overall survival of osteosarcoma is still conflicting, and this meta-analysis was performed to assess these associations.Material and methodsThe association studies were identified from PubMed, and eligible reports were included and calculated using meta-analysis method.ResultsFour studies were included for the association of ERCC gene polymorphism with osteosarcoma risk, and nine studies were recruited into this meta-analysis for the relationship between ERCC gene polymorphism and overall survival of osteosarcoma. The meta-analysis indicated that ERCC1 rs3212986 (8092 C>A) gene polymorphism, ERCC1 rs11615 (19007 T>C) gene polymorphism, ERCC2 rs1799793 (A>G) gene polymorphism, ERCC2 rs13181 (Lys751Gln) gene polymorphism were not associated with osteosarcoma risk. ERCC1 rs2298881 (C>A) gene polymorphism, ERCC1 rs3212986 (8092 C>A) gene polymorphism, ERCC1 rs11615 (19007 T>C) gene polymorphism, ERCC2 rs1799793 (Asp312Asn) gene polymorphism were not associated with overall survival of osteosarcoma. Interestingly, ERCC2 rs13181 A allele and GG genotype were associated with overall survival of osteosarcoma, but AA genotype not (A allele: OR = 0.78, 95% CI: 0.65–0.93, P = 0.007; GG genotype: OR = 1.32, 95% CI: 1.05–1.65, P = 0.02; AA genotype: OR = 0.69, 95% CI: 0.45–1.04, P = 0.08).ConclusionERCC2 rs13181 A allele and GG genotype were associated with overall survival of osteosarcoma.     

Association of STAT4 gene rs7574865G > T polymorphism with ulcerative colitis risk: evidence from 1532 cases and 3786 controls

Introduction

Several studies have reported the relationship between the STAT4 rs7574865G > T polymorphism as a susceptibility factor to ulcerative colitis (UC). However, the results have been controversial. Therefore, we conducted this meta-analysis to obtain the most reliable estimate of the association.

Material and methods

PubMed, Embase and Web of Science databases were searched. Crude odds ratios (OR) with 95% confidence intervals (CI) were extracted and pooled to assess the strength of the association between the STAT4 rs7574865G > T polymorphism and risk of UC. A total of five eligible studies including 1532 cases and 3786 controls based on the search criteria were involved in this meta-analysis.

Results

We observed that the STAT4 rs7574865G > T polymorphism was significantly correlated with UC risk when all studies were pooled into the meta-analysis (the allele contrast model: OR = 1.13, 95% CI = 1.02–1.25; the heterozygote codominant model: OR = 1.22, 95% CI = 1.04–1.43; the dominant model: OR = 1.25, 95% CI = 1.07–1.45). In the stratified analysis by ethnicity, significant associations were observed in Spanish for the allele contrast model (OR = 1.20; 95% CI = 1.04–1.39), for the homozygote codominant model (OR = 1.57; 95% CI = 1.07–2.31), for the dominant model (OR = 1.20; 95% CI = 1.01–1.43), and for the recessive model (OR = 1.50; 95% CI = 1.03–2.19).

Conclusions

This meta-analysis suggests that the STAT4 rs7574865G > T polymorphism is a low-penetrant risk factor for UC, especially in Spanish.     

Interleukin-10 -1082A/G polymorphism is associated with the development of acute pancreatitis in a Chinese population

We conducted a case-control study to investigate the association between IL-10 gene polymorphism (-1082A/G, -819T/C, and -592A/C) and risk of acute pancreatitis in a Chinese population. A total of 240 patients with proven acute pancreatitis and 240 control subjects were collected between May 2012 and January 2015. Genotyping of the IL-10-1082A/G, -819T/C, and -592A/C gene polymorphisms was conducted by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. By univariate logistic regression analysis, patients with acute pancreatitis were more likely to have higher BMI (OR=2.12, 95% CI=1.45-3.12; P<0.001) and have a habit of alcohol drinking (OR=2.01, 95% CI=1.37-2.95; P<0.001). There were significant differences in the genotype distributions of IL-10-1082A/G between patients with acute pancreatitis and control subjects (χ²=9.97, P=0.007). By multiple logistic regression analysis, we found that individuals with the GG genotype of IL-10-1082A/G were associated with an increased risk of acute pancreatitis when compared with the AA genotype (OR=2.32, 95% CI=1.20-4.59; P=0.007). In dominant and recessive models, the IL-10-1082A/G gene polymorphism was significantly correlated with an elevated risk of acute pancreatitis, and the adjusted Ors (95% CI) were 1.50 (1.03-2.20) and 1.99 (1.06-3.79), respectively. However, no significant different was found between IL-10-819T/C and -592A/C gene polymorphisms and susceptibility to acute pancreatitis. In conclusion, we suggest that IL-10-1082A/G gene polymorphisms contribute to the development of acute pancreatitis in codominant, dominant and recessive models.     

Correlation between survivin genetic polymorphisms and lung cancer susceptibility

Aims: The purpose of the study was to analyze the relationship of survivin polymorphisms including -31G/C, -625G/C, 9194A/G and 9809T/C with the susceptibility to lung cancer. Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to test the polymorphisms of -31G/C, -625G/C, 9194A/G and 9809T/C in 104 patients with lung cancer and 104 healthy controls. Then, linkage disequilibrium and haplotypes were analyzed by HaploView software. The differences of genotype, allele and haplotype frequencies in case and control group were assessed via chi-square test. Odds ratio (OR) with 95% CI were used to evaluate the correlation of survivin polymorphisms with lung cancer. Results: Genotype distribution of each polymorphism site in control group was in agreement with Hardy-Weinberg equilibrium (HWE) (P>0.05). The frequency of -31G/C CC genotype and C allele in case group were much higher than that of controls, respectively (CC: 33.6% vs. 22.1%; C: 57.2% vs. 46.6%) and CC genotype as well as C allele were appeared to be risk factors for lung cancer. Meanwhile, 9194A/G GG genotype could increase the risk for lung cancer (OR=2.86, 95% CI=1.14-7.20). The risk of G allele carriers for lung caner was higher than that of A allele (OR=1.63, 95% CI=1.08-2.47). The haplotypes analysis indicated that CGGC and GCAT were associated with the susceptibility to lung cancer (OR=2.79, 95% CI=1.58-4.92; OR=2.36, 95% CI=1.29-4.30). Conclusions: Survivin -31G/C and 9194A/G polymorphisms were associated with the risk of lung cancer. The CGGC and GCAT haplotypes carriers were more likely to develop lung cancer.     

Correlation of interactions between NOS3 polymorphisms and oxygen therapy with retinopathy of prematurity susceptibility

Aim: This study was aimed to detect the correlation of nitric oxide synthase 3 (NOS3) gene polymorphisms (T-786C and G894T) and retinopathy of prematurity (ROP) susceptibility. Interaction between NOS3 gene polymorphisms and the duration of oxygen therapy was also explored in ROP babies. Methods: Genotypes of NOS3 gene polymorphisms were genotyped by MassArray method. Hardy-Weinberg equilibrium (HWE) was used to calculate the representativeness of the cases and controls. Crossover analysis was utilized to explore the gene environment interactions. Relative risk of ROP was presented by odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs). Results: Among the subject features, oxygen therapy had obvious difference between case and control groups (P<0.05). There existed significant association between-786C allele and ROP susceptibility (P=0.049, OR=0.669, 95% CI=0.447-0.999). Genotypes of T-786C polymorphism and genotypes and alleles of G894T polymorphism did not related to the susceptibility of ROP. Interactions were existed between NOS3 gene polymorphisms and oxygen therapy duration. When the duration of oxygen therapy was less than 17 days, both -786CC genotype and 894GT genotype were correlated with ROP susceptibility (P=0.020, OR=0.115, 95% CI=0.014-0.960; P=0.011, OR=0.294, 95% CI=0.100-0.784). Conclusion: -786C allele might have a protective effect for ROP. Interactions of -786CC and 894GT genotype with oxygen therapy duration (less than 17 days) were both protection factors of ROP.     

Association between CTLA-4 gene polymorphism and ankylosing spondylitis: a case-control study

Aims: The aim of our study was to evaluate the association between CTLA-4 polymorphisms (+49A/G, -318C/T and CT60A/G) and ankylosing spondylitis (AS) susceptibility. Methods: A total of 120 AS cases and healthy controls, matched on the age and gender, were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) were used to determine the gentypes of +49A/G, -318C/T and CT60A/G polymorphisms. Genotype distribution in control group was assessed by Hardy Weinberg Equilibrium (HWE) test. Odds ratio (OR) with 95% confidence interval (95% CI) were adopted to evaluate the relationship of CTLA-4 polymorphisms and AS susceptibility. Results: In our study, genotype distribution of the three polymorphisms in control group was consistent with the HWE (P > 0.05). The genotype analysis showed that AA genotype of + 49A/G polymorphism could increase the risk for AS (OR=2.357, 95% CI=1.127-4.930). Moreover, the frequency of A allele was also presented as a risk factor for AS. Additionally, AA genotype and A allele of CT60A/G appeared to be related with AS susceptibility (OR=2.610, 95% CI=1.047-6.510; OR=1.751, 95% CI=1.160-2.641). However, the T allele of -318C/T appeared to be a protective factor for AS (OR=0.383, 95% CI=0.228-0.643). Conclusion: In summary, there existed significant association between CTLA-4 gene polymorphisms and increased or decreased risk for AS.     

Predictive role of miR-146a rs2910164 (C>G), miR-149 rs2292832 (T>C), miR-196a2 rs11614913 (T>C) and miR-499 rs3746444 (T>C) in the development of hepatocellular carcinoma

We conducted a case-control study to evaluate the association of miR-146a rs2910164 (C>G), miR-149 rs2292832 (T>C), miR-196a2 rs11614913 (T>C) and miR-499 rs3746444 (T>C) polymorphisms with the risk of hepatocellular carcinoma. A total of 274 patients with HCC were collected between January 2013 and December 2014. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was taken to determine the polymorphism of miR-146a C>G, miR-149 T>C, miR-196a2 T>C and miR-499 T>C. By comparing with control groups, patients with HCC were more likely to be males (OR=2.01, 95% CI=1.38-2.95), have older age (OR=1.52, 95% CI=1.09-2.13), have a history of alcohol drinking (OR=2.09, 95% CI=1.49-2.93), and be infected with HBV (OR=32.98, 95% CI=19.70-55.46) and HCV (OR=56.26, 95% CI=23.28-152.98) infection. By conditional regression analysis, individuals carrying the TC and CC genotypes of miR-196a2 T>C were found to be associated with an elevated risk of HCC compared to the TT genotype, and the adjusted odds ratio were 1.50 (1.03-2.17) and 2.86 (1.60-5.16), respectively. Moreover, the TC+CC genotype was correlated with an increased risk of HCC (OR=1.69, 95% CI=1.19-2.41) compared to the wide-type genotype. In conclusion, our results suggested that miR-196a2 T>C polymorphism is associated with HCC risk in Chinese population.     

Cyclooxygenase-2 Polymorphisms and Susceptibility to Colorectal Cancer: A Meta-Analysis

Purpose

Four polymorphisms, -765G>C, -1195G>A, 8473T>C, and Val511Ala, in the cyclooxygenase-2 (COX-2) gene were identified to be associated with colorectal cancer (CRC) risk. However, the results are inconsistent. The objective of this meta-analysis was to evaluate the association between these four polymorphisms and the risk of CRC.

Materials and Methods

All eligible case-control studies published up to December 2012 on the association between the four polymorphisms of COX-2 and CRC risk were identified by searching PubMed and Web of Science. The CRC risk associated with the four polymorphisms of the COX-2 gene was estimated for each study by odds ratio (OR) together with its 95 % confidence interval (CI), respectively.

Results

A total of 15 case-control studies were included. Overall, no evidence has indicated that the -1195A allele, -765C allele, 8473C allele, and 511Ala allele are associated with susceptibility to CRC (-1195G>A: OR=1.11, 95 % CI: 0.82-1.51, p=0.78; -765G>C: OR=1.08, 95 % CI: 0.96-1.21, p=0.07; 8473T>C: OR=1.03, 95 % CI: 0.89-1.18, p=0.91; Val511Ala: OR=0.71, 95 % CI: 0.46-1.09, p=0.94). However, stratified analysis with ethnicity indicated that individuals with -765GC or GC/CC genotypes had an increased risk of CRC among Asian populations (GC vs. GG: OR=1.05, 95 % CI: 0.87-1.28, p=0.03; GC+CC vs. GG: OR=1.08, 95 % CI: 0.96-1.21, p=0.07).

Conclusion

This meta-analysis indicated that -765G>C polymorphism was significantly associated with susceptibility to CRC in Asian populations.     

The Interaction Between Allelic Variants of CD86 and CD40LG: A Common Risk Factor of Allergic Asthma and Rheumatoid Arthritis

Purpose

Allergic asthma (AA) and rheumatoid arthritis (RA) are immune tolerance-related diseases, and immune tolerance is known to be influenced by costimulatory molecules. In this study, we sought to identify common genetic susceptibility in AA and RA.

Methods

Two hundred cases of AA, 184 cases of RA, and 182 healthy controls were recruited at the Seoul National University Hospital, Seoul, Korea. Eight single nucleotide polymorphisms (SNPs) in five genes coding costimulatory molecules, namely, -318C>T, +49A>G, and 6230G>A in CTLA4, IVS3+17T>C in CD28, -3479T>G and I179V in CD86, -1C>T in CD40, and -3458A>G in CD40LG were scored, and genetic interactions were evaluated by multifactor dimensionality reduction (MDR) analysis.

Results

MDR analysis revealed a significant gene-gene interaction between -3479T>G CD86 and -3458A>G CD40LG for AA. Subjects with the T/T genotype of -3479T>G CD86 and the A/A genotype of -3458A>G CD40LG were found to be significantly more likely to develop AA than those with the T/T genotype of -3479T>G CD86 and A/- genotype of -3458A>G CD40LG (adjusted OR, 6.09; 95% CI, 2.89-12.98; logistic regression analysis controlled by age). Similarly those subjects showed a significant risk of developing RA (adjusted OR, 39.35; 95% CI, 15.01-107.00, logistic regression analysis controlled by age).

Conclusions

Our findings suggest that a genetic interaction between CD86 and CD40LG favors the development of both AA and RA.     

TNF-α-308G/A polymorphism associated with TNF-α protein expression in patients with diabetic nephropathy

Aims: This study was to clarify the regulated effects of TNF-α -308G/A polymorphism on TNF-α and investigate the relationship of -308G/A polymorphisms with diabetic nephropathy (DN) susceptibility. Methods: 86 DN patients and 94 healthy individuals were enrolled in our study. Polymerase chain reaction-sequence specific primer (PCR-SSP) detection technology was used to testify single nucleotide polymorphism (SNP) of TNF-α gene. Enzyme-linked immunosorbent assay (ELISA) was used to measure the content of TNF-α protein. Odds ratio (OR) with 95% CI were used to evaluate the association of TNF-α -308G/A polymorphism and DN susceptibility. Results: The level of TNF-α protein was much higher in DN patients compared to that of controls (P < 0.05). For TNF-α -308G/A, G/A genotype could increase the risk for DN (OR = 2.15, 95% CI = 1.08-4.30). Moreover, a allele frequency was found higher in cases compared with controls, which suggested that A allele served as an genetic-susceptibility factor for DN (OR = 1.89, 95% CI = 1.10-3.26). Further analysis indicated that level of TNF-α for individuals with mutant genotype (GA and AA) were higher than that of individuals with wild genotype (P < 0.05). However, AA genotype showed no effects on DN susceptibility (OR = 2.08, 95% CI = 0.56-7.33). Conclusion: TNF-α-308G/A polymorphism was associated with expression level of TNF-α and served as an genetic-susceptibility factor for DN.     

Promoter polymorphism T-786C, 894G→T at exon 7 of endothelial nitric oxide synthase gene are associated with risk of osteoporosis in Sichuan region male residents

Objective: To investigate the association between genetic polymorphism of T-786C in promoter region, 894G→T at exon 7 of endothelial nitric oxide synthase (eNOS) gene and osteoporosis (OP) disease. Method: The genotypes of 350 patients with osteoporosis and 350 healthy controls were detected by polymerase chain reaction (PCR) and DNA sequencing. The allele ratios and genotype distributions in the patients and controls were assessed using the Pearson χ²-test. Odds ratios (OR) with two tailed P-values and 95% confidence intervals (CI) were calculated as a measure of the association of the eNOS genotypes with OP. Result: the C allele distribution frequency of T-786C eNOS gene in OP group (8.5%) was significantly higher than that in control group (3.9%), relative risk (OR) of OP associated with the CC genotype was 2.68 (95% CI, 0.92 to 1.37). The T allele frequency of 894G→T at exon 7 in eNOS gene in OP group (11.5%) was also significantly higher than that in control group (5.2%), OR of OP associated with the TT genotype was 2.60 (all P<0.05). Conclusion: The analysis results indicated that both T-786C in promoter region and 894G→T at exon 7 of eNOS gene might be genetic predisposal factors of OP, these polymorphisms may be independently or synergic with other loci to have an impact on the incidence of OP.     

The most frequent Polish ATM mutations are not susceptibility factors for tobacco-related cancers

IntroductionThe inactivation of both alleles of the ATM gene leads to ataxia-telangiectasia syndrome, whereas carriers of monoallelic mutations in the ATM gene are associated with increased risk of different types of cancer. Three substitutions in the ATM gene (c.6095G>A, c.7630-2A>C, c.5932G>T) are the most common mutations causing ataxia-telangiectasia among Polish patients. The aim of this study was to determine whether these ATM mutations are associated with increased risk of tobacco-related cancers.Material and methods783 Polish patients with tobacco-related cancers were included in the study (468 with lung cancer, 153 with a single laryngeal cancer, 86 with multiple primary tumors localized in the larynx and 76 multiple primary tumors localized in the head or neck). The control group consisted of 464 healthy subjects from the Polish population. Three ATM mutations – c.5932G>T, c.6095G>A, c.7630-2A>C – were tested among selected patients. Molecular analyses were performed using high resolution melting analysis and restriction fragment length polymorphism.ResultsIn the present study, we detected only one mutation, c.7630-2A>C, and no carriers of c.5932G>T, c.6095G>A mutations in the ATM gene among Polish patients with tobacco-related cancers. A patient with c.7630-2A>C mutation was diagnosed with lung adenocarcinoma, the most common type of lung cancer. One carrier of c.6095G>A mutation was found in the control group.ConclusionsThe results indicate that the studied ATM variants do not seem to be associated with tobacco-related cancers in Poland.