VDR Gene Polymorphisms,Interaction with Smoking and Risk of Periodontal Disease in Japanese Women: the Kyushu Okinawa Maternal and Child Health Study

Epidemiological evidence on the relationship between vitamin D receptor (VDR) polymorphisms and periodontal disease is inconsistent. We investigated associations between four VDR single‐nucleotide polymorphisms (SNPs) including rs731236 (TaqI), rs7975232 (ApaI), rs1544410 (BsmI) and rs2228570 (FokI), and the risk of periodontal disease among young Japanese women. Cases included 131 women who had at least one tooth with a probing depth of 3.5 mm or deeper. Controls included 1019 women without periodontal disease. Adjustment was made for age, region of residence, education, toothbrushing frequency and use of an interdental brush. Compared with the AA genotype of SNP rs731236, the GG genotype had a significantly increased risk of periodontal disease: the adjusted OR was 3.68 (95% confidence interval: 1.06–12.78). There were no significant relationships between SNPs rs7975232, rs1544410 or rs2228570 and periodontal disease. None of the haplotypes were significantly related to periodontal disease. Compared with subjects with the AA or AG genotype of SNP rs731236 who had never smoked, those with the GG genotype who had ever smoked had a significantly increased risk of periodontal disease; nevertheless, neither multiplicative nor additive interaction was significant. The additive interaction between SNP rs7975232 and smoking was significant, although the multiplicative interaction was not statistically significant. No multiplicative or additive interactions were observed between the other SNPs and smoking. Our results indicated that VDR SNP rs731236 might be associated with periodontal disease. In addition, we present new evidence for a biological interaction between VDR SNP rs7975232 and smoking that affects periodontal disease.     

Haplotypes of RHO polymorphisms and susceptibility to age-related macular degeneration

Objective: To investigate whether haplotypes of rhodopsin (RHO) polymorphisms including rs7984, rs2855552, rs2855557 and rs2410 were associated with age-related macular degeneration (AMD) risk in Chinese Han population. Methods: Genotypes of rs7984, rs2855552, rs2855557 and rs2410 were detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 186 cases and 196 healthy controls. Then, the haplotypes were established with Haploview 4.2 software. And the effects of clinical charactersitics on the frequency of GTTG haplotype were also analyzed. Odds ratios (ORs) with 95% confidence interval (95% CI) were utilized to assess the relationship of haplotypes and genotypes of RHO polymorphisms with susceptibility to AMD. Results: Genotype distribution of all polymorphisms in control group were all in agreement with Hardy-Weinberg equilibrium (HWE) (P>0.05). In the analysis, we found that mutant alleles of rs7984 and rs2855557 were both associated with increased risk of AMD. For genotype analysis, rs7984 AA and rs2855557AA, rs2410GG genotypes all could increase the risk for AMD (OR=1.905, 95% CI=1.143-3.174; OR=2.226, 95% CI=1.261-3.932; OR=2.073, 95% CI=1.105-3.888). However, rs2855552 showed no effects on the onset of AMD. Compared with GTTA, the haplotypes of GGTG, ATAA and GTTG were all related with AMD susceptibility. Further analysis suggested that age, hypertension and hyperlipidemia history play important roles in the frequency alteration of GTTG haplotype. Conclusion: RHO polymorphisms (rs7984, rs2855557 and rs2410) and haplotypes may confer remarkable susceptibility to AMD. Further investigation showed that gene and environmental factors may work together in the pathogenesis of AMD.     

CX3CR1 polymorphisms and the risk of age-related macular degeneration

Background: Age-related macular degeneration (AMD), a most common eye disease, can lead to irreversible visual impairment. Age, genetic and environmental factors have been implicated in AMD. Chemokine (C-X3-C motif) receptor 1 (CX3CR1) gene polymorphisms could influence the susceptibility of AMD. Methods: We tested the association between AMD and single nocleotide polymorphisms (SNPs) of CX3CR1 gene (rs3732378 and rs3732379) in 102 cases and 115 controls from China. Genotypes were determined by MassArray genotyping assay method. Association between CX3CR1 gene polymorphisms and AMD were examined by χ² test and logistic regression. Results: Genotype distribution of CX3CR1 gene polymorphisms were in accordance with HWE examination. No obvious differences were observed in the genotypes of rs3732378 polymorphism between case and control groups (P>0.05), but A allele of it could increase the risk of AMD (P=0.025, OR=2.391, 95% CI=1.092-5.237). Both TT genotype and T allele of rs3732379 were significantly associated with the susceptibility of AMD (P=8.663, OR=8.663, 95% CI=1.044-71.874; P=0.021, OR=2.076, 95% CI=1.104-3.903). Age, gender and smoking status were used as common confounders to adjust the association between CX3CR1 gene polymorphism and AMD risk. Then we found that rs3732378 had no obvious association with AMD susceptibility. TT genotype of rs3732379 related to the occurrence of AMD, but the association was not significant (P=0.050, OR=8.274, 95% CI=1.002-69.963). T allele of rs3732379 might increase the susceptibility of AMD (P=0.029, OR=2.033, 95% CI=1.077-3.838). Conclusion: T allele of rs3732379 might have a positive association with the susceptibility of AMD.     

Association of dietary and supplemental folate intake and polymorphisms in three FOCM pathway genes with colorectal cancer in a population‐based case‐control study

Previous research has shown that greater intakes of dietary folate are associated with reduced risk for colorectal cancer (CRC) and that single nucleotide polymorphisms (SNPs) in genes involved in folate‐mediated one‐carbon metabolism (FOCM) also may be involved in altering CRC risk. The objective of this study was to evaluate the role of folate intake (and intakes of related dietary components such as methionine), 35 SNPs in three FOCM pathway genes (MTHFD1, MTHFR, and TYMS), and their interactions on CRC risk in a population‐based case‐control study in Pennsylvania (686 cases, 740 controls). Diet and supplement use was assessed for the year before diagnosis or interview for cases and controls, respectively, with a modified Diet History Questionnaire from the National Cancer Institute. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. Using a dominant model for the variant allele, several SNPs were significantly associated with CRC including MTHFD1 rs8003379 (OR = 1.65; 95% CI = 1.00?2.73) and rs17824591 (OR = 1.98; 95% CI = 1.14?3.41) and the TYMS rs2853533 SNP (OR = 1.38; 95% CI = 1.05?1.80). Using a nondominant model, the AA genotype for MTHFR rs1476413 exhibited a marginally significant (OR = 1.56; 95% CI = 1.00?2.44) association with CRC. Two TYMS SNPs (rs16948305 and rs495139) exhibited significant (P = 0.024 and P = 0.040, respectively) gene‐diet interactions with folate intake. One MTHFD1 (P = 0.019) and one MTHFR (P = 0.042) SNP exhibited gene‐diet interactions with methionine intake. These findings suggest that allelic variants in genes involved in FOCM interact with dietary factors including folate and methionine to modify risk for CRC. © 2013 Wiley Periodicals, Inc.     

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.     

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.     

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.     

Polymorphisms of xenobiotic‐metabolizing genes and colorectal cancer risk in patients with lynch syndrome: A retrospective cohort study in Taiwan

Cytochrome P450 (CYP), glutathione‐S‐transferase (GST), and N‐acetyltransferase (NAT) are crucial for metabolism and clearance of xenobiotics. This study investigated whether CYP, GST, and NAT single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in patients with Lynch syndrome. The interaction between these SNPs and cigarette smoking or meat consumption was also explored. We identified 270 patients with Lynch syndrome from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs). The GSTA1 rs3957356 TT (HR = 5.36, 95% CI = 2.39–12.0) and CYP1B1 rs1056836 CC (HR = 7.24, 95% CI = 3.51–14.9) were significantly associated with CRC risk when compared to wild‐type CC and GG genotypes, respectively. However, the CYP1A1 rs4646903 CC genotype significantly reduced the risk of CRC (HR = 0.33, 95% CI = 0.12–0.89) when compared to TT genotype. Moreover, significant interactions were observed between NAT1 acetylation and CYP1B1 rs1056827 and meat consumption.Our results suggest that xenobiotic‐metabolizing SNPs are not only associated with CRC risk in patients with Lynch syndrome in Taiwan but also interact with meat consumption to modify the disease risk. Environ. Mol. Mutagen. 59:69–78, 2018. © 2017 Wiley Periodicals, Inc.     

Association between PKA gene polymorphism and NTDs in high risk Chinese population in Shanxi

Objective: This study aimed to investigate the single nucleotide polymorphisms (SNPs) of PKA and neural tube defects (NTDs) in Chinese population. Method: A total of 183 NTDs cases and 200 healthy controls were used in this study. 7 selected single nucleotide polymorphism (SNP) sites in the PKA gene were analyzed with MassArray high-throughput DNA analyzer with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. A series of statistical methods were carried out to investigate the correlation between the SNPs and the patient susceptibility to NTDs. Results: Statistical analysis showed a significant correlation between the SNP sites rs12132032 in PRKACB and NTDs. The AA genotype, A-allele and dominant AA in rs12132032 significantly increased the incidence of NTDs especially anencephaly (OR=3.87, 95% CI: 1.80-8.34 with genotype; OR=2.08, 95% CI: 1.43-3.04 with allele; OR=3.10, 95% CI: 1.53-6.26 with dominant). The T-allele of rs594631 in PRKACB was correlative with NTDs in male but not in female. Conclusions: The gene polymorphism loci rs12132032 in PRKACB maybe a potential risk factor for anencephaly in Chinese population from Shanxi, while gender susceptibility may influence the correlation.     

Estrogen receptor alpha gene (ESR1) polymorphism and its interaction with smoking and drinking contribute to susceptibility of systemic lupus erythematosus

The aim of this study is to investigate the association of estrogen receptor alpha gene (ESR1) polymorphisms, additional gene–gene, and gene–environment interaction with systemic lupus erythematosus (SLE) risk. SNPStats (available online at http://bioinfo.iconcologia.net/SNPstats) was used to investigate the Hardy–Weinberg equilibrium (HWE) in controls and association between SNP and SLE risk. Generalized multifactor dimensionality reduction (GMDR) was used to screen the interactions among SNPs and environmental risk factors; SLE risk was significantly higher in carriers of rs2234693 C allele than those with TT (TC + CC versus TT), adjusted OR (95%CI) = 1.57 (1.21–2.06), and was also higher in carriers of rs9340799 G allele than those with AA (AG + GG versus AA), adjusted OR (95%CI) = 1.68 (1.24–2.13). However, we also find no association between rs2228480 and SLE risk after covariates adjustment. We found a significant two-locus model (p = 0.0010) involving rs2234693 and smoking; the cross-validation consistency of this model was 10/10, and the testing accuracy was 62.70%. Smokers with TC or CC of rs2234693 genotype have the highest SLE risk, compared to never-smokers with TT of rs2234693 genotype, OR (95%CI) was 2.50 (1.65–3.42), after covariates adjustment for gender, age, alcohol drinking, and BMI. We found that C allele of rs2234693 and G allele of rs9340799 within ESR1 gene, their interaction between rs2234693 and current smoking were all associated with increased SLE risk.     

Association of ALOX5AP gene single nucleotide polymorphisms and cerebral infarction in the Han population of northern China

ABSTRACT: BACKGROUND: To explore the association of ALOX5AP single nucleotide polymorphisms (SNPs) and haplotype with the occurrence of cerebral infarction in the Han population of northern China. METHODS: Blood samples were collected from 236 patients of Han ancestry with a history of cerebral infarction and 219 healthy subjects of Han ancestry with no history of cerebral infarction or cardiovascular disease. Applied Biosystems(R) TaqMan(R) SNP Genotyping Assays for SNP genotyping were used to determine the genotypes of 7 ALOX5AP SNP alleles (rs4073259, rs4769874, rs9315050, rs9551963, rs10507391, rs9579646, and rs4147064). RESULTS: One SNP allele (A) of rs4073259 was significantly associated with development of cerebral infarction (P = 0.049). In comparison to control groups, haplotype rs9315050&rs9551963 AAAC [OR (95 % CI) =1.53 (1.02-2.29)], and genotypes rs4147064 CT [OR (95 % CI) =1.872 (1.082-3.241)], and rs9551963 AC [OR (95 % CI) = 2.015 (1.165-3.484)] increased the risk of cerebral infarction in patients with hypertension. Genotype rs9579646 GG [OR (95 % CI) = 2.926 (1.18-7.251)] increased the risk of, while rs4073259 GG [OR (95 % CI) = 0.381 (0.157-0.922)] decreased the risk of cerebral infarction in patients with diabetes. CONCLUSION: These results suggest the ALOX5AP SNP A allele in rs4073259 and genotype rs9579646 GG, rs9551963 AC, and haplotype rs9315050 & rs9551963 AAAC were associated with an increased risk of ischemic stroke in the Han population, while rs4073259 GG was associated with a decreased risk.     

β2肾上腺素受体基因Arg16Gly位点多态性与华南人群哮喘相关性研究

目的探讨β2肾上腺素受体基因(ADRB2)SNP位点rs1042713即突变位点Arg16Gly的多态性与华南汉族人群支气管哮喘发病的相关性。方法采用病例对照研究,利用基质辅助激光解吸电离飞行时间质谱技术(MALDI-TOF-MS)对rs1042713进行基因分型,对实验结果运用χ2检验和二分类Logistic回归进行统计学相关性分析。结果 rs1042713多态位点AA、AG、GG 3种基因型在哮喘患者的频率为18.7%、76.0%和5.3%,与对照组(33.8%,44.6%和21.6%)相比具有显著差异(χ2=36.28,P<0.001);对年龄和性别进行校正后,发现相对于AA+GG基因型,携带AG基因型的哮喘发病风险增加(OR=4.37,95%CI:2.64~7.23)。结论华南汉族人群哮喘的发病机制可能与SNP rs1042713位点的单核苷酸多态性有关,杂合子基因型AG为其发病的危险因素。     

IL3 rs40401 Polymorphism and Interaction with Smoking in Risk of Asthma in Japanese Women: The Kyushu Okinawa Maternal and Child Health Study

Three previous genetic association studies conducted in Korea and China investigated the relationship between IL3 single nucleotide polymorphism (SNP) rs40401 and asthma, but their results were inconsistent. We examined this relationship and the possibility of an interaction between IL3 SNP rs40401 and smoking in young adult Japanese women. Included were 89 women who met the criteria of the European Community Respiratory Health Survey (ECRHS) for asthma. Control subjects were 700 women without asthma according to the ECRHS criteria who had not been diagnosed with asthma and/or allergic rhinitis by a doctor and/or who had not met the criteria of the International Study of Asthma and Allergies in Childhood for rhinoconjunctivitis. A significant positive association was found between SNP rs40401 and the risk of asthma, with the TT genotype as the reference under the additive model: the adjusted odds ratio was 1.39 (95% CI: 1.004–1.93). The positive association was not statistically significant in any other genetic model. Compared with subjects with the TT or TC genotype of SNP rs40401 who had never smoked, those with the CC genotype who had ever smoked had a significantly increased risk of asthma: the adjusted OR was 2.67 (95% CI: 1.23–5.79); the additive interaction, but not the multiplicative interaction, was significant. This study suggests that IL3 SNP rs40401 is significantly associated with the risk of asthma in young adult Japanese women and reveals that the combination of ever smoking and having the CC genotype of IL3 SNP rs40401 is significantly positively associated with asthma.     

SOD2 V16A SNP in the Mitochondrial Targeting Sequence is Associated with Noise Induced Hearing Loss in Chinese Workers

Objective: To investigate whether single nucleotide polymorphisms (SNPs) in the Mn-superoxide dismutase gene (SOD2) underlie the susceptibility to noise-induced hearing loss (NIHL). Methods: Audiometric data from 2400 Chinese Han workers who exposed to occupational noise were analyzed. DNA samples were collected from the 10% most susceptible and the 10% most resistant individuals, and five SNPs (SOD2 rs2842980, rs5746136, rs2758331, rs4880 and rs5746092) were genotyped by Taqman SNP Genotyping Kits. The SNP main effects and interactions between noise exposure and SNP were analyzed using logistic regression. Haplotypes were analyzed by using Haploview software. Results: The CT genotype of rs4880 (SOD2 V16A SNP) was associated with a higher risk of NIHL (covariates-adjusted OR, 2.18; 95% CI, 1.34–3.54, P = 0.002). Haplotype analysis revealed that the frequency of AGCCG at the five SNP loci was significantly higher in the susceptible group (P = 0.020). With AGCTG as the reference, the OR (95% CI) was 2.63 (1.14, 6.06). The rs4880 polymorphisms imposed larger effects when the carriers were exposed to higher levels of noise, indicating the interaction between SNP and noise exposure. Conclusions: Our results suggest that SOD2 V16A SNP in the mitochondrial targeting sequence is associated with noise induced hearing loss in Chinese workers, and this effect was enhanced by higher levels of noise exposure.     

Association between interluekin-17 gene polymorphisms and the risk of cervical cancer in a Chinese population

We conducted a study to analyze the association of three common SNPs of IL-17A rs2275913 and rs3748067 and IL-17F rs763780 gene polymorphisms with the risk of cervical cancer in a Chinese population. Our study included 352 cervical cancer patients and 352 controls between January 2013 and December 2014. Genotyping of IL-17A rs2275913 and rs3748067 and IL-17F rs763780 genes was performed by multiplex PCR assays using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). By χ² test, there was significantly difference in the genotype distribution of IL-17A rs2275913 between cervical cancer patients and control subjects (χ²=11.45, P=0.003). By conditional logistic regression analysis, we found that individuals with the GA and AA genotypes were associated with an increased risk of cervical cancer when compared with the GG genotype in codominant model, and the adjusted Ors (95% CI) were 1.57 (1.13-2.18) and 2.01 (1.15-3.49), respectively. In dominant model, we found that the GA+AA genotype of rs2275913 was correlated with a moderate increased risk of cervical cancer compared with the GG genotype (OR=1.64, 95% CI=1.20-2.24). We only found significant interaction between rs2275913 polymorphism and HPV-16 or 18 infection in the risk of cervical cancer (P for interaction <0.05). In conclusion, our study suggests that IL-17A rs2275913 polymorphism may affect the development of cervical cancer in codominant and dominant models, and this gene polymorphism has interaction with HPV-16 or 18 infection.     

The Association between the Polymorphisms in a Sodium Channel Gene SCN7A and Essential Hypertension: A Case‐Control Study in the Northern Han Chinese

Na_x, an α‐subunit of the sodium channel encoded by the SCN7A gene, has been deemed to be a sensor of the concentration of sodium in the brain and may be involved in salt intake behavior. We inferred that Na_x/SCN7A may participate in the regulation of blood pressure and the pathogenesis of essential hypertension (EH). The present case‐control study involving 615 hypertensives and 617 normotensives was performed to investigate the association between SCN7A polymorphisms and EH in the Northern Han Chinese population. The three common single nucleotide polymorphisms (SNPs) (rs3791251, rs6738031, rs7565062) in the exons of SCN7A were genotyped with the TaqMan assay. Significant association between SNP rs7565062 and EH was found under the addictive and dominant genetic models (P = 0.024, OR = 1.283, 95%CI [1.033–1.592]; P = 0.013, OR = 1.203, 95%CI [1.040–1.392]; respectively). The three SNPs were in close pair‐wise linkage disequilibrium with each other and the haplotype analyses indicated that haplotype G–A–T was significantly associated with increased risk of EH (P = 0.023, OR = 1.290). In conclusion, our data showed that SNP rs7565062 of SCN7A was significantly associated with EH and the allele T of rs7565062 or the related haplotype G–A–T will be a genetic risk factor for EH in the Northern Han Chinese population.     

Genetic Factors in Nonsmokers with Age‐Related Macular Degeneration Revealed Through Genome‐Wide Gene‐Environment Interaction Analysis

Relatively little is known about the interaction between genes and environment in the complex etiology of age‐related macular degeneration (AMD). This study aimed to identify novel factors associated with AMD by analyzing gene‐smoking interactions in a genome‐wide association study of 1207 AMD cases and 686 controls of Caucasian background with genotype data on 668,238 single nucleotide polymorphisms (SNPs) after quality control. Participants’ history of smoking at least 100 cigarettes lifetime was determined by a self‐administered questionnaire. SNP associations modeled the effect of the minor allele additively on AMD using logistic regression, with adjustment for age, sex, and ever/never smoking. Joint effects of SNPs and smoking were examined comparing a null model containing only age, sex, and smoking against an extended model including genotypic and interaction terms. Genome‐wide significant main effects were detected at three known AMD loci: CFH (P = 7.51×10^?30), ARMS2 (P = 1.94×10^?23), and RDBP/CFB/C2 (P = 4.37×10^?10), while joint effects analysis revealed three genomic regions with P < 10^?5. Analyses stratified by smoking found genetic associations largely restricted to nonsmokers, with one notable exception: the chromosome 18q22.1 intergenic SNP rs17073641 (between SERPINB8 and CDH7), more strongly associated in nonsmokers (OR = 0.57, P = 2.73 × 10^?5), with an inverse association among smokers (OR = 1.42, P = 0.00228), suggesting that smoking modifies the effect of some genetic polymorphisms on AMD risk.     

GATA5基因启动子序列单核苷酸多态性可增加急性心肌梗死的易感性

目的:通过病例-对照研究,探讨GATA结合蛋白5(GATA binding protein 5,GATA5)基因启动子序列单核苷酸多态性(single nucleotide polymorphism,SNP)与急性心肌梗死(acute myocardial infarction,AMI)的相关性。方法:通过χ~2检验、logistic回归、单倍型分析、细胞转染及电泳迁移率变动分析(electrophoretic mobility shift assay,EMSA)对SNPs进行遗传及功能分析。结果:校正混杂因素后,rs80197101位点GA和GA+AA基因型与AMI显著相关(OR=2.280,95%CI:1.027~5.061,P=0.043;OR=2.312,95%CI:1.045~5.116,P=0.039)。rs77067995位点CT和CT+TT基因型也与AMI显著相关(OR=2.280,95%CI:1.027~5.061,P=0.043;OR=2.312,95%CI:1.045~5.116,P=0.039)。rs80197101和rs77067995呈完美连锁不平衡,两者形成的单倍型AT在AMI组的频率显著高于对照组(χ~2=6.960,P=0.008)。EMSA及转染结果表明,这些SNPs通过影响转录因子与GATA5基因启动子的结合,显著增加GATA5基因启动子在HEK-293细胞和H9c2细胞中的转录活性(P<0.001)。结论:GATA5基因启动子序列中的rs80197101与rs77067995可显著增加AMI的易感性。rs80197101的等位基因A和rs77067995的等位基因T可能是AMI的危险等位基因,单倍型AT可能是AMI的危险单倍型。     

IL8 and IL17A polymorphisms associated with multibacillary leprosy and reaction type 1 in a mixed population from southern Brazil

We evaluated the influence of the IL8 T‐738A (nonidentified rs), IL8 T‐353A (rs4073), IL17A G197A (rs2275913), and IL17F T7488C (rs763780) single‐nucleotide polymorphisms on leprosy. The AA genotype of IL8 T‐353A was observed as a risk factor for multibacillary leprosy, regardless of gender and age‐of‐onset of disease, considering the recessive model (OR, 3.8; 95% CI, 1.1–13.5; P, 0.023). Furthermore, the AA genotype of IL17A G197A was associated with leprosy type 1 reaction (OR, 2.4; 95% CI, 1.1–5.1; P, 0.026) when compared to the group without reaction, which was adjusted for gender and age‐of‐onset of disease by the model log additive. These results indicate association of IL8 and IL17A polymorphisms with the progression to multibacillary leprosy and with the type 1 reaction, respectively.