ABCB1 polymorphisms associated with osteonecrosis of the femeral head

Aims: This case-control study was conducted to investigate the relation of ATP-binding cassette subfamily B member 1 (ABCB1) C1236T and C3435T polymorphisms and non-traumatic osteonecrosis of the femeral head (ONFH). Methods: We gathered 113 ONFH patients and 116 controls in the study. The polymorphisms of ABCB1 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. Odds ratio (OR) with 95% confidence interval (CI) were adopted to analyze the correlation between ABCB1 polymorphisms and ONFH. Results: In the study, we found that the frequency of C3435T TT genotype was much lower in case group, compared with that of controls (17.7% vs. 23.3%). Moreover, OR and 95% CI values indicated that C3435T TT genotype served as a protective factor for ONFH (OR=0.34, 95% CI=0.15-0.75). Meanwhile, the risk for the T allele carriers was much lower than C allele (OR=0.60, 95% CI=0.42-0.87). However, C1236T polymorphism showed no significant effects on the pathogenesis of ONFH. In the haplotype analysis, T-T haplotype appeared to be an inhibitor for ONFH (OR=0.45, 95% CI=0.23-0.87). Conclusions: Based on the results, ABCB1 polymorphisms were associated with the risk for ONFH.     

Correlation between LSP1 polymorphisms and the susceptibility to breast cancer

Objective: The present study aimed at assessing the relationship between Leukocyte-specific protein 1 gene (LSP1) polymorphisms (rs569550 and rs592373) and the pathogenesis of breast cancer (BC). Methods: 70 BC patients and 72 healthy subjects were enrolled in the study. Rs569550 and rs592373 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratio (OR) with 95% confidence interval (CI) were calculated by the chi-squared test to assess the relationship between LSP1 polymorphisms and BC risk. Linkage disequilibrium (LD) and haplotypes were also analyzed by HaploView software. Results: Genotype distribution of the control was in accordance with Hardy-Weinberg equilibrium (HWE). The homozygous genotype TT and T allele of rs569550 could significantly increase the risk of BC (TT vs. GG: OR=3.17, 95% CI=1.23-8.91; T vs. G: OR=1.63, 95% CI=1.01-2.64). For rs592373, mutation homozygous genotype CC and C allele were significantly associated with BC susceptibility (CC vs. TT: OR=4.45, 95% CI=1.38-14.8; C vs. T: OR=1.70, 95% CI=1.03-2.81). LD and haplotypes analysis of rs569550 and rs592373 polymorphisms showed that T-C haplotype was a risk factor for BC (T-C vs. G-T: OR=1.74, 95% CI=1.04-2.92). Conclusion: LSP1 rs569550 and rs592373 polymorphisms are both risk factors for BC.     

Associations between TNFSF15 polymorphisms and susceptibility to ulcerative colitis and Crohn's disease: A meta-analysis

Abstract

Aims: Several polymorphisms have been identified in TNFSF15, while their roles in the incidence of ulcerative colitis (UC) and Crohn's disease (CD) are conflicting. This meta-analysis was aimed to clarify the impact of these polymorphisms on UC and CD risk. Method: Databases were searched until 31 January 2014 for eligible studies on TNFSF15 polymorphisms. Data were extracted, and pooled odd ratios (ORs) as well as 95% confidence intervals (95% CIs) were calculated. Results: Fifteen studies with 8903 CD patients, 4687 UC patients and 12?606 controls were included. Except for rs4263839 polymorphism, significant associations were found between the rest six TNFSF15 polymorphisms and CD risk (rs3810936: OR?=?2.10, 95% CI, 1.47–3.00; rs6478108: OR?=?2.19, 95% CI, 1.53–3.13; rs4979462: OR?=?1.89, 95% CI, 1.42–2.52; rs6478109: OR?=?2.00, 95% CI, 1.39–2.88; rs7848647: OR?=?1.54, 95% CI, 1.15–2.06; rs7869487: OR?=?1.51, 95% CI, 1.06–2.17). And we found rs3810936, rs6478108 and rs6478109 polymorphism were significantly associated with UC risk (rs3810936: OR?=?1.19, 95% CI, 1.06–1.34; rs6478108: OR?=?1.16, 95% CI, 1.06–1.26; rs6478109: OR?=?1.16, 95% CI, 1.03–1.32). According to the subgroup analysis by ethnicity, except for rs4263839 in Caucasian and rs4979462 in Asian, all the rest investigated TNFSF15 polymorphisms were associated with CD risk and rs3810936 and rs7848647 polymorphism in Asian as well as rs6478108 polymorphism in Caucasian were associated with UC risk. Conclusion: This meta-analysis indicated that most of the seven TNFSF15 polymorphisms (except for rs4263839) were risk factors contributed to CD and UC susceptibility. The differences in ethnicity did not influence the risk obviously.     

Association between ACE polymorphisms and osteoarthritis susceptibility

Objective: The present study was designed to investigate the association of angiotensin-converting enzyme (ACE) rs4343 and rs4362 polymorphisms with the susceptibility to osteoarthritis (OA). Methods: 109 knee OA patients and 114 healthy people were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to perform the genotyping for two groups and the linkage disequilibrium and haplotype were analyzed using Haploview software. The differences of genotype and allele frequencies were analyzed by χ² test and Fisher’s exact test. The relationship between ACE polymorphisms and OA susceptibility was represented by odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: The genotypes distributions of ACE rs4343 and rs4362 polymorphisms in control groups were accordance with HWE. ACE rs4343 polymorphism was associated with the significantly increased risk of OA (AG vs. AA: OR=2.41, P=0.003; GG vs. AA: OR=5.35, P=0.015; G vs. A: OR=2.27, P<0.001). Similarly, rs4362 polymorphisms was also a risk factor for OA (CT vs. CC: OR=2.60, P=0.005; TT vs. CC: OR=3.15, P=0.003; T vs. C: OR=1.88, P=0.001). The result of haplotype analysis showed complete linkage disequilibrium in rs 4343 and rs 4362 polymorphisms. The G-T haplotype significantly increased OA susceptibility, but A-C is a protective factor for the occurrence of OA. Conclusion: Significant correlation exists between ACE rs4343 and rs4362 polymorphisms and OA. In haplotype analysis, A-C haplotype may provide protection against OA, and G-T haplotype may be a risk factor for the development of OA.     

Association between ERAP1 gene polymorphisms and ankylosing spondylitis susceptibility in Han population

Purposes: The present study was designed to investigate the relationship between endoplasmic reticulum amino peptidase 1 (ERAP1) gene polymorphisms and ankylosing spondylitis (AS) in Han population of Shaanxi province. Methods: 100 AS patients and 100 healthy people were enrolled in present study as case and control groups respectively, and the control group was matched with the case group by age and gender. ERAP1 gene rs27434 and rs7711564 polymorphisms were test by TaqMan probe genotyping method. SHEsis software was used to operate linkage disequilibrium (LD) and haplotype analysis between the two single nucleotide polymorphisms (SNPs). χ² test was employed to compare the differences of the genotype, allele and haplotype frequencies between the case and control groups. Relative risk of AS was represented by odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: In ERAP1 rs27434 and rs7711564 polymorphisms, the frequencies of AA and CC genotypes in case group were significantly higher compared to those in control group (P=0.036; P=0.039), and so were the frequencies of A and C alleles (OR=1.589, 95% CI=1.070-2.359, P=0.028; OR=1.535, 95% CI=1.021-2.308, P=0.050). Linkage disequilibrium test and haplotype analysis of the alleles of the two SNPs showed that the frequency of A-C haplotype was higher in case group than that in control group (P=0.005), which indicated that A-C might be the susceptible haplotype to AS. Conclusions: ERAP1 gene rs27434 and rs7711564 polymorphisms may increase the risk of AS.     

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.     

Relationship between hWAPL polymorphisms and cervical cancer susceptibility

Purpose: To analyze the correlation of the polymorphisms of human wing-apart like (hWAPL) gene (rs7083506 and rs11202058) with the susceptibility to cervical cancer. Besides, the relationship of haplotypes between the polymorphisms with cervical cancer susceptibility was analyzed. Methods: Taqman probe genotyping method was adopted to detect the genotype distribution of hWAPL rs7083506 and rs11202058 polymorphisms in 117 cervical cancer patients and 128 healthy controls. Linkage disequilibrium and haplotypes were analyzed by Haploview software. χ² test was utilized to analyze the differences of genotype, allele and haplotype frequencies between the case and control groups. Results: Correlation analysis of hWAPL rs7083506 and rs11202058 polymorphisms with cervical cancer susceptibility was based on the five genetic models. TT genotype of rs7083506 increased the susceptibility of cervical cancer in TT vs. CC model and TT vs. CT+TT model (OR=2.249, 95% CI=1.018-4.970; OR=2.287, 95% CI=1.069-4.896). For rs11202058, the A allele increased the cervical cancer susceptibility (A vs. G, OR=1.502, 95% CI=1.005-2.245). No significant correlation was observed between rs11202058 genotypes and cervical cancer susceptibility. We performed the haplotype analysis between the two polymorphisms, and found that T-A haplotype significantly correlated with cervical cancer, the susceptibility of cervical cancer increased to 1.78 times. Conclusions: Rs7083506 and rs11202058 polymorphisms of hWAPL and their haplotype T-A were associated with cervical cancer.     

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.     

Protective role of interleukin-19 gene polymorphisms in patients with ulcerative colitis

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) of unknown etiology. Interleukin (IL)-19 belongs to the IL-10 family and is a potent immunomodulatory cytokine, with implications for pathogenesis in IBD. No previous studies have reported this novel association between UC and IL-19 polymorphisms. In the present work, the role of IL-19 gene polymorphisms as susceptibility markers for UC was evaluated. Three polymorphisms of IL-19 gene (rs2243188, rs2243191, and rs2243193) were genotyped by 5' exonuclease TaqMan genotyping assays on an ABI Prism 7900 HT Fast Real-Time PCR System in a group of 200 Mexican Mestizo patients with UC and 698 healthy unrelated individuals with no family history of UC. The rs2243191 polymorphism significantly deviated from Hardy-Weinberg equilibrium (HWE) (p < 0.05) and consequently was not included in the analysis. Although genotypes AA (rs2243188) and AA (rs2243193) were significant decreased in UC patients as compared with healthy controls (p(c) = 0.018 and p(c) = 0.006, respectively), a genetic additive effect for the alleles was not observed (Cochran-Armitage trend test, not significant). In the subgroup analysis, no differences were found between the IL-19 genotypes and the clinical characteristics of UC. The results suggest that IL-19 polymorphisms (rs2243188 and rs2243193) might have a protective role in the development of UC in Mexican individuals.     

Association between EGFR polymorphisms and the risk of lung cancer

Target: The study aimed to investigate the role of epidermal growth factor receptor (EGFR) rs6965469 and rs763317 polymorphisms in the occurrence and development of lung cancer. Methods: We used polymerase chain reaction-ligation detection reaction (PCR-LDR) method to detect the genotypes of EGFR rs6965469 and rs763317 polymorphisms and the data were analyzed by GeneMapper software. Odds ratios (ORs) with 95% confidence intervals (CIs) was calculated by χ² test to estimate the significance difference of genotype and allele frequencies in case and control groups. ORs and 95% CIs were adjusted by logistic regression analysis with age, gender, drinking and smoking. The genotypes distributions of control group were tested by Hardy-Weinberg equilibrium (HWE). Results: The genotypes frequencies of controls for rs6965469 and rs763317 polymorphims were consistent with HWE. The distribution of rs6965469 TT genotype in two groups was significantly different (P<0.05) and TT genotype was associated with an increased risk of lung cancer (OR=6.92, 95% CI=1.33-36.00). AA genotype and A allele of rs763317 were also the susceptible factors of lung cancer. Individuals with AA genotype or A allele were more likely to suffer lung cancer (AA vs. GG: OR=7.20, 95% CI=1.33-39.07; A vs. G: OR=2.61, 95% CI=1.04-6.59). Conclusions: The EGFR rs6965469 and rs763317 polymorphisms may be risk factors for lung cancer.     

Klotho gene polymorphisms are related to colorectal cancer susceptibility

Aim: The purpose of this study was to investigate the relationship of Klotho gene G-395A and C1818T polymorphisms with colorectal cancer (CRC) susceptibility. Methods: 125 CRC patients and 125 controls were enrolled in the study. G-395A and C1818T polymorphisms were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. Haploview software was utilized to conduct linkage disequilibrium and haplotype analysis. Odds ratio (OR) and 95% confidence interval (95% CI) were used to analyze the correlation of genotypes and haplotypes with CRC susceptibility. Results: AA and GA genotypes of G-395A polymorphisms were related with CRC risk (AA: OR = 4.161, 95% CI = 1.437-12.053; GA: OR = 1.958, 95% CI = 1.133-3.385). The frequency of A allele was much higher in case group, compared with controls (31.2% vs.17.6%) and the value of OR AND 95% CI suggested that A allele served as a risk factor for CRC (OR = 2.123, 95% CI = 1.393-3.236). Haplotypes analysis indicated that A-C and A-T haplotypes were significantly associated with risk of CRC (OR = 1.822, 95% CI = 1.124-2.954; OR = 2.877, 95% CI = 1.340-6.176). Conclusion: G-395A polymorphism of Klotho gene could increase the risk of CRC.     

Association between interleukin-10 gene promoter polymorphisms and susceptibility to liver cirrhosis

We conducted a case-control study to investigate the association between three common SNPs in IL-10 gene (rs1800896, rs1800871 and rs1800872) and the development of liver cirrhosis in a Chinese population. Between January 2013 and December 2014, a total of 318 patients with liver cirrhosis and 318 health control subjects were enrolled into our study. The IL-10 rs1800896, rs1800871 and rs1800872 polymorphisms were analyzed using polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By multivariate logistic regression analysis, we found that individuals with the AA genotype and GA+AA genotype of IL-10 rs1800896 were more likely to have an increased risk of liver cirrhosis when compared with the GG genotype, and the ORs (95% CI) for the AA genotype and GA+AA genotype were 2.04 (1.20-3.50) and 1.41 (1.02-1.96), respectively. We found that the GA+AA genotype of IL-10 rs1800896 had higher risk of liver cirrhosis in individuals with chronic hepatitis B when compared with the GG genotype (OR = 1.95, 95% CI = 1.01-3.59). In conclusion, we found that IL-10 rs1800896 polymorphism was correlated with an increased risk of liver cirrhosis, especially in individuals with chronic hepatitis B.     

Association between COX-2 polymorphisms and non-small cell lung cancer susceptibility

Aim: To explore the association between COX-2 polymorphisms and non-small cell lung cancer (NSCLC) susceptibility. Methods: We collected fasting peripheral venous blood from 60 cases with NSCLC and 62 healthy controls through physical examinations, and applied PCR-RFLP to analyze COX-2 polymorphisms of two groups. Results: With respect to detecting COX-2 rs689466 and rs5275 polymorphisms, the distribution frequency of mutant genotype AA of COX-2 rs689466 in case group was higher than that in control group, which possessed significant difference between two groups (P < 0.05). Carriers with AA genotype were 4.05 times at risk of NSCLC than those with GG genotype (P = 0.04, OR=4.05, 95% CI = 1.14-14.43). The distribution of mutant genotype CC of COX-2 rs5275 was different between two groups, and carriers with genotype CC were at 5.70 times higher risk of NSCLC than those with genotype TT. After corrected by sex, gender, smoking and drinking factors, AA genotype of COX-2 rs689466 and CC genotype of COX-2 rs5275 still contributed to increased risk of NSCLC (OR=4.22, 95% CI=1.10-16.17, OR=6.95, 95% CI=1.27-38.11). After analyzed of linkage disequilibrium (LD) and haplotypes of alleles in two SNPs, the distribution frequency of A-C haplotype in case group was higher than that in control group, with significant difference between two groups (P < 0.05). After corrected by sex, gender, smoking and drinking factors, statistical difference was still found in the total distribution of A-C haplotype between two groups (P = 0.03, OR=6.11, 95% CI=1.16-32.2). Conclusions: COX-2 rs689466 and rs5275 polymorphisms may be related to NSCLC susceptibility. And A-C haplotype might be a susceptibility haplotype for NSCLC.     

HLA-B is the best candidate of susceptibility genes in HLA for Japanese ulcerative colitis

Recently, a genome-wide association study for ulcerative colitis (UC) in the UK population was reported, and several susceptibility loci including the human leukocyte antigen ( HLA ) region were identified. The strongest association in the HLA region was found at a 400 kb haplotype block containing HLA-DRB1 . In Japanese population, previous study suggested the association between UC and HLA-B*52 ; however, HLA typing was determined using serotyping with the small sample size. The purpose of this study was to perform an association study in HLA-B by genotyping. A total of 320 patients with UC and 322 healthy controls were recruited in this case–control study. All subjects were Japanese. Genotyping of HLA-B was performed by polymerase chain reaction using a sequence-specific primer. When the allele frequencies were compared, significant associations were found with B*52 [odds ratio (OR) = 3.65, P  = 1.6 × 10⁻¹⁷, P _c = 3.7 × 10⁻¹⁶] and B*4002 (OR = 0.52, P  = 0.00030, P _c = 0.0068). The allele frequency of B*52 was significantly higher in patients diagnosed before 40 years of age than in those diagnosed after 40 years (OR = 1.79, P  = 0.010, P _c = 0.020). A combination association map of Japanese UC using our current and previous studies showed two equal peaks of association on HLA-DRB1 and HLA-B , indicating the possible existence of two casual variants in the HLA region inside and outside the 400 kb block found in UK. We conclude that HLA-B contributes to the susceptibility to Japanese UC, especially cases with younger age of onset. The strength of association for HLA-B was equal to that for HLA-DRB1 in Japanese UC, in contrast to the UK population.     

Association of SLC11A1 (NRAMP1) polymorphisms with pulmonary Mycobacterium avium complex infection

Although genetic variants in SLC11A1 (NRAMP1) have been associated with mycobacterial diseases, these findings have not been extensively validated in pulmonary Mycobacterium avium complex (MAC) infection. This study investigated the genomic structure of SLC11A1 and its association with MAC infection. Nineteen polymorphic loci were genotyped in European descendents and the Japanese population. Linkage disequilibrium (LD) structures and frequencies of major haplotypes differed between these 2 populations. Tag single nucleotide polymorphisms (SNPs) were chosen from the data set, and 6 polymorphic sites were genotyped in 122 pulmonary MAC cases and 211 controls from Japan. We observed that the T allele of rs2279014 in the 3' untranslated region was associated with protection from MAC disease when comparing allele frequencies with an odds ratio of 0.582 (95% confidence interval 0.379-0.894, p = 0.013). The frequencies of haplotypes constructed with the above 6 variants did not differ between cases and controls. Allele-specific expression imbalance of SLC11A1 mRNA was evaluated in peripheral blood cells from heterozygous individuals, but no difference was observed among haplotypes. Although the significance was modest, rs2279014 is in strong LD with nearby SNPs and further studies are required for conclusive validation.     

CTLA-4 gene polymorphisms and susceptibility to chronic obstructive pulmonary disease

Objective: The aim of this study was to investigate whether four single nucleotide polymorphisms (SNPs) in CTLA-4 gene are associated with chronic obstructive pulmonary disease (COPD) in a Chinese population. Methods: Samples were collected from a Chinese population and analyzed for the association of SNPs in CTLA-4 gene with COPD in a case-control study. Four SNPs (rs231775, rs3087243, rs231725, rs5742909) in CTLA-4 gene were chosen and genotyped. The results were then analyzed using statistical methods. Results: We found that none of these four SNPs (rs231775, rs3087243, rs231725, rs5742909) in CTLA-4 gene were associated with the disease. Conclusion: Our data suggested that there was no significant association between these four SNPs in CTLA-4 gene and COPD susceptibility in a Chinese population.     

Association of complement factor H gene polymorphisms with age-related macular egeneration susceptibility

Objective: This study was aimed to confirm whether I62V and Y402H polymorphisms of complement factor H (CFH) were risk factors for age-related macular degeneration (AMD). Method: 109 AMD patients and 165 AMD-free controls were enrolled in the study. The I62V and Y402H polymorphisms were analyzed by polymerase chain reaction-restriction fragment length of polymorphism (PCR-RFLP). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by the X² test to assess the relationship of I62V and Y402H polymorphisms with AMD risk. Analysis of haplotype and stratification by age and smoking status was conducted as well. Results: AA genotype and A allele of I62V polymorphism was significantly associated with increased risk for AMD (OR = 3.75, 95% CI = 1.70-8.30; OR = 1.64, 95% CI = 1.14-2.36). For Y402H polymorphism, CT genotype showed strong effects on the occurrence of AMD (OR = 2.10, 95% CI = 1.04-4.27). Moreover, C allele was also a risk factor for AMD (OR = 1.95, 95% CI = 1.02-3.72). The haplotypes analysis suggested that the risk for AT haplotype carriers was high, compared with GT haplotype (OR = 3.91, 95% CI = 2.58-5.94). In addition, we found that smoking status could affect the genotype distribution of Y402H polymorphism (P < 0.05). Conclusions: Our results revealed that CFH polymorphisms I62V and Y402H might be associated with the susceptibility to AMD in Chinese population.     

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.     

CREB1 gene polymorphisms combined with environmental risk factors increase susceptibility to major depressive disorder (MDD)

Major depressive disorder (MDD) is one of the most severe psychiatric disorders. The objective of this study was to explore the effects of CREB1 gene polymorphisms on risk of developing MDD and the joint effects of gene-environment interactions. Genotyping was performed by Taqman allelic discrimination assay among 586 patients and 586 healthy controls. A significant impact on rs6740584 genotype distribution was found for childhood trauma (P = 0.015). We did not find an association of CREB1 polymorphisms with MDD susceptibility. However, we found a significantly increased risk associated with the interactions of CREB1 polymorphisms and drinking (OR = 11.67, 95% CI = 2.52-54.18; OR = 11.52, 95% CI = 2.55-51.95 for rs11904814; OR = 4.18, 95% CI = 1.87-9.38; OR = 5.02, 95% CI = 2.27-11.14 for rs6740584; OR = 7.58, 95% CI = 2.05-27.98; OR = 7.59, 95% CI = 2.12-27.14 for rs2553206; OR = 8.37, 95% CI = 3.02-23.23; OR = 7.84, 95% CI = 2.93-20.98 for rs2551941). We also noted that CREB polymorphisms combined with family harmony and childhood trauma conferred increased susceptibility for MDD. In conclusion, polymorphisms in the CREB gene may not be independently associated with MDD risk, but they are likely to confer increased susceptibility by interacting with environmental risk factors in the Chinese population.     

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.