Multifactor Dimensionality Reduction Method Research Articles

The associations of IGF2, IGF2R and IGF2BP2 gene polymorphisms with gestational diabetes mellitus: A case-control study.

To investigate the associations of Insulin-like growth factor-II (IGF2) gene, Insulin-like growth factor-II receptor (IGF2R) gene and Insulin-like growth factor-II binding protein 2 (IGF2BP2) gene polymorphisms with the susceptibility to gestational diabetes mellitus (GDM) in Chinese population. A total of 1703 pregnant women (835 GDM and 868 Non-GDM) were recruited in this case-control study. All participants underwent prenatal 75 g oral glucose tolerance test (OGTT) examinations during 24-28 gestational weeks at the Maternal and Child Health Hospital of Hubei Province from January 15, 2018 to March 31, 2019. Genotyping of candidate SNPs (IGF2 rs680, IGF2R rs416572, IGF2BP2 rs4402960, rs1470579, rs1374910, rs11705701, rs6777038, rs16860234, rs7651090) was performed on Sequenom MassARRAY platform. Logistic regression analysis was conducted to investigate the associations between candidate SNPs and risk of GDM. In addition, multifactor dimensionality reduction (MDR) method was applied to explore the effects of gene-gene interactions on GDM risk. There were significant distribution differences between GDM group and non-GDM group in age, pre-pregnancy BMI, education level and family history of diabetes (P < 0.05). After adjusted for age, pre-pregnancy BMI, education level and family history of diabetes, there were no significant associations of the candidate SNPs polymorphisms and GDM risk (P > 0.05). Furthermore, there were no gene-gene interactions on the GDM risk among the candidate SNPs (P > 0.05). However, the fasting blood glucose (FBG) levels of rs6777038 CT carriers were significantly lower than TT carriers (4.69±0.69 vs. 5.03±1.57 mmol/L, P < 0.01), and the OGTT-2h levels of rs6777038 CC and CT genotype carriers were significantly lower than TT genotype carriers (8.10±1.91 and 8.08±1.87 vs. 8.99±2.90 mmol/L, P < 0.01). IGF2 rs680, IGF2R rs416572, IGF2BP2 rs4402960, rs1470579, rs11705701, rs6777038, rs16860234, rs7651090 polymorphisms were not significantly associated with GDM risk in Wuhan, China. Further lager multicenter researches are needed to confirm these results.

Variations in the Cadherin 23 Gene Associated With Noise-Induced Hearing Loss.

The relationship between CDH23 gene variants and NIHL is unclear. This study investigates the association between cadherin 23 (CDH23) gene variants and noise-induced hearing loss (NIHL). This is a case-control study. Workers who were exposed to noise from a steel factory in North China were recruited and divided into two groups: the case group (both ears' high-frequency threshold average [BHFTA] ≥40dB) and the control group (BHFTA ≤25 dB). This study used the generalised multifactor dimensionality reduction method to analyse the association among 18 single-nucleotide polymorphisms (SNPs) in CDH23 and NIHL. Logistic regression was performed to investigate the main effects of SNPs and the interactions between cumulative noise exposure (CNE) and SNPs. Furthermore, CNE was adjusted for age, gender, smoking, drinking, physical exercise and hypertension. This study recruited 1,117 participants. The results showed that for rs11592462, participants who carried the GG genotype showed an association with NIHL greater than that of those who carried the CC genotype. Accordingly, genetic variation in the CDH23 gene could play an essential role in determining individual susceptibility to NIHL. Genetic variations in the CDH23 gene may play an important role in determining individual susceptibility to NIHL. These results provide new insight into the pathogenesis and early prevention of NIHL.

Association between PRKG1 Gene and Gene-Environment Interactions with Pediatric Asthma

ABSTRACT Objective To investigate the relationship between single nucleotide polymorphisms (SNPs) of cGMP-dependent protein kinase I (PRKG1) gene and gene-environment interactions with bronchial asthma in children. Methods 109 asthma patients and 158 healthy controls from the General Hospital of Northern Theater Command were enrolled, based case–control study. The iMLDR® multiple SNP typing technique was applied to detect the genotypes of rs7903366, rs7081864, rs7070958 and rs7897633 in PRKG1 gene. The percentage of eosinophils (EOS%) in peripheral blood and serum immunoglobulin E (IgE) in the case group were also measured. Gene-environment interactions were examined using the generalized multi-factor dimensionality reduction (GMDR) method. Results There were polymorphisms in four SNPs of PRKG1 gene in the case and control groups. The genotype and allele frequencies distribution of rs7897633 demonstrated statistical significance (p < 0.05). There were no statistically significant differences in EOS% and IgE among genotypes at the four SNPs of PRKG1 gene (p > 0.05). The haplotypes CAGA and TGAC presented significant association with asthma risk (p < 0.05). The four-factor model indicated a potential gene-environment interaction in rs7897633, allergen exposure, residence, and environmental tobacco smoke (ETS) exposure (p < 0.05). Conclusions The rs7897633 in PRKG1 gene was associated with susceptibility to childhood asthma, and C allele is a protective factor. The haplotype CAGA had a protective effect against asthma risk and TGAC was linked to the high risk of developing asthma. Moreover, the interaction of rs7897633, allergen exposure, residence, and ETS exposure conferred susceptibility to childhood asthma.

Association of SOX6 gene polymorphisms with Kashin-Beck disease risk in the Chinese Han population.

Kashin-Beck disease (KBD) is an endemic osteochondropathy. A specific gene called SRY-box transcription factor 6 (SOX6) is important for forming cartilage. This study aims to explore the potential correlation between SOX6 single nucleotide polymorphisms (SNPs) and KBD risk for the first time. In the case-control study, 735 unrelated Chinese Han individuals were enrolled. The four mutation sites of the SOX6 gene (rs4539287 G/A, rs3203295 C/A, rs7928675 C/A, and rs10832681 A/G) were screened and genotyped on the Agena MassARRAY platform. The correlation between SOX6 SNPs and KBD risk was explored based on logistic regression analysis. The interaction between SNP and SNP was analyzed based on the multi-factor dimensionality reduction (MDR) method. Overall analysis revealed a remarkable correlation between rs7928675 and rs10832681 and the reduction of KBD risk (p < 0.05). Subgroup analyses further indicated that these two SNPs have a significant protective effect on KBD risk among participants aged ≤65 years, males, and non-smokers (p < 0.05). MDR displayed a marked interaction between rs3203295 and rs10832681. Our study revealed that SOX6 rs7928675 and rs10832681 are markedly correlated with a reduced risk of KBD in the Chinese Han population, providing a new direction for the prevention, diagnosis, and treatment of KBD.

Interaction between maintenance variables of medical ultrasound scanners through multifactor dimensionality reduction

ABSTRACT Background Proper maintenance of electro-medical devices is crucial for the quality of care to patients and the economic performance of healthcare organizations. This research aims to identify the interaction between Ultrasound scanners (US) maintenance variables as a function of maintenance indicators: US in service or decommissioned, excessive number of failures, and failure rate. Knowing those interactions, specific maintenance measures will be developed to improve the reliability of the US. Research design and methods Multifactor Dimensionality Reduction (MDR) method was eployed to analyze data from 222 US and their four-year maintenance history. Models were developed based on the variables with the greatest influence on maintenance indicators, where US were classified according to the associated risk. Results US with more than one major failure or at least one major component replacement had up to 496.4% more failures than the average. Failure rate increased by up to 188.7% over the average for those US with more than three moderate failures, three replacements, or both. Conclusions This study identifies and quantifies the causes of risk to establish a specific maintenance plan for US. It helps to better understand the degradation of US to optimize their operation and maintenance.

Impact of TREM1 Variants on the Risk and Prognosis of Glioma in the Chinese Han Population.

Glioma is the main pathological subtype of brain tumors with high mortality. This study aimed to elucidate the correlation between TREM1 variants and glioma risk in the Chinese Han population. Genotyping of six variants of TREM1 was completed by Agena MassARRAY platform in 1061 subjects (503 controls and 558 glioma patients). The relationship between TREM1 polymorphisms and glioma risk was calculated using the logistic regression model, with odds ratio (OR) and 95% confidence intervals (CIs). A multifactor dimensionality reduction (MDR) method was performed to assess SNP-SNP interactions to predict glioma risk. In this research, overall analysis illustrated an association between TREM1 rs9369269 and an increased risk of glioma. Rs9369269 was also related to the risk of glioma in patients aged ≤40 years and females. Subjects with rs9369269 AC genotype were likely to obtain glioma compared to people with CC genotype (patients with astroglioma vs healthy people). Compared to TT genotype carriers, carriers with AT genotype of rs1351835 were significantly associated with overall survival (OS). Taken together, the study identified the association between TREM1 variants and glioma risk and TREM1 variants were significantly associated with the prognosis of glioma. In the future, larger samples are needed to verify the results.

Association between GLS Gene Polymorphisms and the Susceptibility to Lung Cancer in the Chinese Han Population.

Lung cancer is one of the most serious malignant tumors endangering human health and life. This study focused on evaluating the association between single nucleotide polymorphisms (SNPs) of the glutaminase (GLS) and lung cancer susceptibility in the Chinese Han population. A total of 684 lung cancer patients and 684 healthy individuals were enrolled. Five GLS SNPs (rs143584207 C/A, rs117985587 T/C, rs74271715 G/T, rs2355570 G/A, and rs6713444 A/G) were screened as candidate genetic loci. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the association between GLS SNPs and lung cancer susceptibility. False-positive report probability (FPRP) analysis further verified whether the positive results deserved attention. Finally, the multi-factor dimensionality reduction (MDR) method was applied to analyze the interactions between SNPs. The overall analysis revealed that GLS rs143584207 and rs6713444 were significantly associated with lung cancer susceptibility. The subgroup and clinical information analyses further revealed that GLS rs143584207 and rs6713444 could remarkably reduce lung cancer susceptibility in different subgroups (age >60, females, body mass index (BMI) <24, and lung adenocarcinoma). Rs143584207 could significantly reduce lung cancer susceptibility in non-smokers. Additionally, rs6713444 also had a protective effect on patients with advanced lung cancer. Our study indicated that GLS rs143584207 and rs6713444 could strikingly reduce lung cancer susceptibility in the Chinese Han population, which will give a new direction for the timely treatment of lung cancer.

Effect of OR51E1 single nucleotide polymorphisms on glioma susceptibility in the Chinese Han population

BackgroundGlioma is one of the common primary intracranial tumors, which is heterogeneous among individuals with a low cure rate. Our study aimed to investigate the association between single nucleotide polymorphisms (SNPs) of the OR51E1 gene and glioma susceptibility in the Chinese Han population. MethodsA total of six SNPs on OR51E1 in 1,026 subjects (526 cases and 500 controls) were genotyped by MassARRAY iPLEX GOLD assay. The association between these SNPs and glioma susceptibility was analyzed using logistic regression, and odds ratios (ORs) and 95% confidence intervals (CIs) were also calculated. The multifactor dimensionality reduction (MDR) method was applied to detect “SNP-SNP” interactions. ResultsIn the overall sample, polymorphisms rs10768148, rs7102992, and rs10500608 were identified to be associated with glioma risk. In the stratified analysis based on gender, only polymorphism rs10768148 was observed to be associated with the risk of glioma. In the age-stratified analysis, rs7102992, rs74052483, and rs10500609 contributed to the risk of glioma in subjects aged > 40 years. And polymorphisms rs10768148 and rs7102992 were associated with the risk of glioma in subjects aged ≤ 40 years and subjects with astrocytoma. In addition, a strong synergistic relationship between rs74052483 and rs10768148, and a strong redundant relationship between rs7102992 and rs10768148 were identified in the study. ConclusionsThis study demonstrated the association of OR51E1 polymorphisms with glioma susceptibility, providing a basis for assessing glioma risk-associated variants in the Chinese Han population.

Multifactor dimensionality reduction method identifies novel SNP interactions in the WNT protein interaction networks that are associated with recurrence risk in colorectal cancer.

Interactions among genetic variants are rarely studied but may explain a part of the variability in patient outcomes. In this study, we aimed to identify 1 to 3 way interactions among SNPs from five Wnt protein interaction networks that predict the 5-year recurrence risk in a cohort of stage I-III colorectal cancer patients. 423 patients recruited to the Newfoundland Familial Colorectal Cancer Registry were included. Five Wnt family member proteins (Wnt1, Wnt2, Wnt5a, Wnt5b, and Wnt11) were selected. The BioGRID database was used to identify the proteins interacting with each of these proteins. Genotypes of the SNPs located in the interaction network genes were retrieved from a genome-wide SNP genotype data previously obtained in the patient cohort. The GMDR 0.9 program was utilized to examine 1-, 2-, and 3-SNP interactions using a 5-fold cross validation step. Top GMDR 0.9 models were assessed by permutation testing and, if significant, prognostic associations were verified by multivariable logistic regression models. GMDR 0.9 has identified novel 1, 2, and 3-way SNP interactions associated with 5-year recurrence risk in colorectal cancer. Nine of these interactions were multi loci interactions (2-way or 3-way). Identified interaction models were able to distinguish patients based on their 5-year recurrence-free status in multivariable regression models. The significance of interactions was the highest in the 3-SNP models. Several of the identified SNPs were eQTLs, indicating potential biological roles of the genes they were associated with in colorectal cancer recurrence. We identified novel interacting genetic variants that associate with 5-year recurrence risk in colorectal cancer. A significant portion of the genes identified were previously linked to colorectal cancer pathogenesis or progression. These variants and genes are of interest for future functional and prognostic studies. Our results provide further evidence for the utility of GMDR models in identifying novel prognostic biomarkers and the biological importance of the Wnt pathways in colorectal cancer.

PIK3R3 Missense and NOTCH2 Synonymous Single Nucleotide Polymorphisms Are Associated with Liver Cancer

Background: Single nucleotide polymorphism (SNP) of candidate genes also affects the occurrence and prognosis of liver cancer. We mainly explored the effects of PIK3R3 and NOTCH2 polymorphisms on liver cancer risk among Chinese people. Methods: Four SNPs (rs785468, rs785467, rs3795666, and rs17024525 in PIK3R3 and NOTCH2) from 709 liver cancer patients and 700 healthy controls were genotyped using the Agena MassARRAY system. The correlation between SNPs and liver cancer risk was evaluated using logistic regression analysis. The SNP-SNP interactions were conducted by the multifactor dimensionality reduction method. Results: The results revealed that PIK3R3-rs785467 reduced the likelihood of liver cancer among Chinese Han people (p < 0.05). In addition, PIK3R3-rs785467 decreased the susceptibility to liver cancer in different populations (females, non-smokers, and age >55 years, p < 0.05). NOTCH2-rs3795666 reduced the susceptibility to liver cancer among males, drinkers, and patients aged >55 years (p < 0.05). Conclusions: Our results demonstrate that PIK3R3-rs785476 and NOTCH2-rs3795666 polymorphisms are responsible for decreasing the susceptibility of liver cancer development in the Chinese Han population.

P2X3-P2X7 SNPs and Gene-Gene and Gene-Environment Interactions on Pediatric Asthma

ABSTRACT Background To investigate the relationship between polymorphisms of P2X3, P2X7 genes and environment interaction with susceptibility of childhood asthma. Methods We conducted a matched case-control study with 170 cases and 175 healthy controls. The rs10896611, rs2276038, rs3781899 in P2X3 and rs1718119, rs3751143 in P2X7 polymorphisms were genotyped using the technique of an improved multiplex ligation detection reaction. Gene-gene, gene-environment and haplotype-environment interactions were tested using the generalized multi-factor dimensionality reduction method. Results There were no differences between cases and controls in allele or genotype frequencies of P2X3 and P2X7. The C/C, G/C genotypes of rs10896611, and C/C, C/T genotypes of rs2276038 and G/G, G/A genotypes of rs3781899 were associated with asthmatic cough (p>0.05),. The haplotype GCT of P2X3 reduced the risk of asthma (OR = 0.48, p = 0.048), and the haplotypes AGT (OR = 0.45, p = 0.001) and GCC (OR = 2.16, p = 0.002) were associated with asthmatic cough. The haplotype AA of P2X7 increased risk of asthma severity (p<0.05). The three-locus model indicated a potential haplotype-environment interaction in GCT, ETS, and pet (p = 0.001). Conclusions The rs10896611, rs2276038 and rs3781899 of P2X3 minor alleles increased the risk of asthmatic cough. Haplotype GCT of P2X3 was a protective factor for asthma, the haplotype AGT was a protective factor and GCC was a risk factor for asthma with cough. In addition, the interactions of haplotype GCT of P2X3, ETS and pet may increase an individual’s susceptibility to asthma.

CYP11B1 gene polymorphisms and susceptibility to ischemic stroke in a Chinese Han population.

Ischemic stroke (IS) is the major cause of death and disability. While previous studies confirmed that CYP11B1 is closely associated with IS, the present study aimed to analyze the impact of CYP11B1 gene polymorphisms on the IS susceptibility. The present study genotyped six single nucleotide polymorphisms (SNPs) (including rs4736312, rs5017238, rs5301, rs5283, rs6410, and rs4534) of CYP11B1 in peripheral blood samples from IS and control populations. Logistic regression analysis was used to analyze the association between the SNPs and IS risk. The multifactor dimensionality reduction (MDR) method was used to determine the roles of SNP-SNP interactions in IS. The present study showed that rs5283 was associated with an increased susceptibility to IS [odds ratio (OR) 1.81, p = 0.012]. On the contrary, rs6410 had a protective influence on IS risk (OR 0.56, p = 0.020). Stratified analyses indicated that rs5283 could enhance the risk of IS in subjects aged >63 years (OR 2.41, p = 0.011), of female gender (OR 3.31, p = 0.001), that do not smoke (OR 1.64, p = 0.005), and with hypertension (OR 2.07, p = 0.003). Whereas, rs6410 was related to a lower susceptibility to IS in subjects aged >63 years (OR 0.43, p = 0.032), of female gender (OR 0.30, p = 0.006), do not smoke (OR 0.42, p = 0.017), and with hypertension (OR 0.52, p = 0.022). Besides, rs4736312 reduced the IS susceptibility in non-smokers (OR 0.69, p = 0.031). Rs4534 had a risk-decreasing impact on IS in non-drinking (OR 0.54, p = 0.016). Moreover, the results of the MDR analysis corroborate that the best prediction model for IS was rs5283. This study revealed that CYP11B1 gene polymorphisms strongly correlated with IS in the Chinese Han population.

Effects of long-term exposure to major outdoor air pollutants for the risk of chronic inflammatory airway diseases in adults with potential interaction detection in Taiwan Biobank

BackgroundResearch on the association between chronic inflammatory airway diseases (CIADs), defined as asthma, chronic obstructive pulmonary disease, and impaired lung function, and long-term exposure of outdoor air pollutants for adults has been scarce. Research questionEffects of long-term exposure for outdoor air pollutants to the risk of CIADs in adults. Materials and methodsApplying data from Taiwan Biobank, 10-year accumulative exposure of major outdoor air pollutants, PM2.5, PM10, NO2, SO2, CO, and O3, was estimated by Kriging's interpolation, based on 76 nationwide air pollution monitoring stations linked to residency information at township or district level at baseline interview for volunteered community participants older than 30 years old. Eligible cases and randomly selected healthy controls constructed a nested case-control study with frequency matching on age and sex at a ratio of 1:4. We adopted logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of outdoor air pollutants to the risk of CIADs for univariable and multivariable analyses. For detecting potential interactions among critical covariates, we used the generalized multifactor dimensionality reduction method. ResultsHigher 10-year cumulative exposure of NO2 and SO2 put people at a significantly elevated relative risk of CIADs after confounding control, showing adjusted ORs of 1.07 (95% CI: 1.01, 1.14) for NO2 and 1.23 (95% CI: 1.15, 1.31) for SO2 for each increment of standard deviation. Furthermore, a significant synergistic interaction (P-value < 0.01 for interaction term) between PM10 and CO in tertiles was detected with an adjusted OR of 5.01 (95% CI: 2.95, 8.49) for the highest tertiles of PM10 and CO combined, relative to the group of lowest tertile combination. ConclusionOur outcomes contributed to a more profound understanding on the effects of long-term exposure of air pollutants to CIADs in etiology, highlighting a synergistic interaction between PM10 and CO.

Association of maternal MTHFD1 and MTHFD2 gene polymorphisms with congenital heart disease in offspring

To study the association of maternal methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) gene polymorphisms with congenital heart disease (CHD) in offspring. A hospital-based case-control study was conducted. The mothers of 683 children with CHD alone who attended Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group, and the mothers of 740 healthy children who attended the same hospital during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect related exposure data, and then venous blood samples (5 mL) were collected from the mothers to detect MTHFD1 and MTHFD2 gene polymorphisms. A multivariate logistic regression analysis was used to evaluate the association of MTHFD1 and MTHFD2 gene polymorphisms with CHD. The four-gamete test in Haploview 4.2 software was used to construct haplotypes and evaluate the association between haplotypes and CHD. The generalized multifactor dimensionality reduction method and logistic regression analysis were used to examine gene-gene interaction and its association with CHD. The multivariate logistic regression analysis showed that maternal MTHFD1 gene polymorphisms at rs11849530 (GA vs AA: OR=1.49; GG vs AA: OR=2.04) andat rs1256142 (GA vs GG: OR=2.34; AA vs GG: OR=3.25) significantly increased the risk of CHD in offspring (P<0.05), while maternal MTHFD1 gene polymorphisms at rs1950902 (AA vs GG: OR=0.57) and MTHFD2 gene polymorphisms at rs1095966 (CA vs CC: OR=0.68) significantly reduced the risk of CHD in offspring (P<0.05). The haplotypes of G-G-G (OR=1.86) and G-A-G (OR=1.35) in mothers significantly increased the risk of CHD in offspring (P<0.05). The gene-gene interaction analyses showed that the first-order interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and the second-order interaction involving MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966 might be associated with risk of CHD (P<0.05). Maternal MTHFD1 and MTHFD2 gene polymorphisms and their haplotypes, as well as the interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and between MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966, are associated with the risk of CHD in offspring.

Role of intergenic interactions among folate cycle genes in the development of fetal growth retardation

Objective: Metabolic disturbances in the folate cycle in mothers can lead to fetal growth retardation (FGR). This study was to analyze the role of intergenic interactions among maternal folate cycle genes in the development of FGR. Methods: This case-control study recruited 365 women in the third trimester of pregnancy, including 122 FGR patients and 243 controls. The women were genotyped for 5 polymorphisms of the 4 folate cycle genes: MTR (rs1805087), MTRR (rs1801394), serine hydroxymethyl transferase (SHMT1; rs1979277), and TYMS (rs699517 and rs2790). The SNP × SNP interactions in the two-, three-, and four-locus models were analyzed using the multifactor dimensionality reduction method and a modification of it (the model-based multifactor dimensionality reduction method). Results: Four loci of maternal folate cycle genes (rs1805087 MTR, rs2790 TYMS, rs1801394 MTRR, and rs1979277 SHMT1) were associated with FGR in 3 significant models of single nucleotide polymorphism (SNP) × SNP interactions (two-, three-, and four-locus models) (P &lt;0.05). The highest contribution to FGR was made by polymorphic loci rs1979277 SHMT1 (1.70% of entropy), rs1805087 MTR (0.96%), and interactions between rs1979277 SHMT1 × rs1805087 MTR (-1.11%) and rs1801394 MTRR × rs1979277 SHMT1 (−0.64%). The four-locus maternal genotype combination AG rs1801394 MTRR × AA rs1805087 MTR × CT rs1979277 SHMT1 × AG rs2790 TYMS was associated with an increased risk of FGR (β = 2.69, P = 0.012). FGR-associated SNPs were correlated with the expression of 16 genes (MTR, MTRR, SHMT1, ALKBH5, CTD-2303H24.2, ENOSF1, FAM106A, FOXO3B, LGALS9C, LLGL1, MIEF2, NOS2P2, RP11-806L2.6, SMCR8, TOP3A, and USP32P2) in various tissues and organs related to FGR pathophysiology. Conclusion: SNP × SNP interactions of maternal folate cycle genes (MTR, MTRR, SHMT1, and TYMS) are associated with the development of FGR.

RORA polymorphisms are risk factors for allergic rhinitis susceptibility in the Shaanxi Han population

BackgroundAllergic rhinitis (AR) is the most common inflammatory disorder induced by complex interactions between genetic and environmental factors. Genetic predisposition is the most important factor in the progression of AR. Previous studies have indicated that RORA is involved in the occurrence of AR. The present study aimed to determine the roles of RORA polymorphisms in AR susceptibility. MethodsPeripheral blood samples were collected from 990 patients with AR and 1004 normal controls. Four single nucleotide polymorphisms (SNPs) in the RORA gene were detected by MassARRAY iPLEX platform. The associations of RORA polymorphisms with AR risk were determined according to logistic regression analysis. We further evaluated the impact of SNP-SNP interaction on AR risk using multifactor dimensionality reduction (MDR) method. ResultsOur results showed that rs10519067 (OR 0.38, p = 0.021), rs10519068 (OR 0.45, p = 0.030), and rs11071559 (OR 0.83, p = 0.032) were significantly related to a decreased susceptibility to AR. Stratified analyses found that rs10519067 (OR 0.71, p = 0.046) and rs10519068 (OR 0.63, p = 0.010) could decrease the risk of AR in males.Rs10519068 (OR 0.73, p = 0.022), rs11071559 (OR 0.77, p = 0.041), and rs9302216 (OR 0.38, p = 0.017) significantly reduced the susceptibility to AR in people aged > 43 years. Furthermore, it was found that rs10519067 (OR 0.29, p = 0.032), rs10519068 (OR 0.72, p = 0.013), and rs11071559 (OR 0.36, p = 0.015) had a protective effect on AR patients with BMI ≤ 24 kg/m2. MDR revealed that the combination of rs10519067, rs10519068, rs11071559, and rs9302216 was the best predictive model for AR. ConclusionOur study suggests that RORA polymorphisms may play a protective role in the development of AR.

SNPs of FOXO1 and Their Interactions Contributes to the Enhanced Risk of Diabetes Among Elderly Individuals.

We have assessed the impact of three single nucleotide polymorphisms (SNPs) of Forkhead Box O1 (FOXO1) and their interaction on susceptibility of type 2 diabetes mellitus in geriatric population from northern India. We genotyped three SNPs (rs2721068, rs17446614, and rs4581585) of FOXO1 gene in 190 elderly individuals with diabetes and 182 unrelated healthy controls of similar ethnicity by using TaqMan SNP assays. SNP-SNP and SNP-environment interactions among polymorphic loci were studied by the multifactor dimensionality reduction (MDR) method. The AA genotype carriers of rs17446614 was associated with the increased susceptibility of diabetes in both adjusted and unadjusted model, whereas rs4581585 was associated with the risk in unadjusted model only. Genotype and minor allele interaction with quantitative parameters revealed that AA genotype of rs17446614 had significantly higher fasting plasma glucose (FPG) in diabetic subjects, also minor allele (A) in patients was positively associated with FPG and glycated hemoglobin. Haplotype Trs2721068Grs17446614Trs4581585 increases the risk of diabetes, whereas carrier of haplotypes Crs2721068Grs17446614Crs4581585 and Crs2721068 Grs17446614Trs4581585 were protective. The MDR analysis revealed that interaction of rs17446614 with body mass index (BMI) increased the susceptibility of diabetes. Therefore presence of rs17446614 variant and its interaction with BMI and haplotype Trs2721068Grs17446614Trs4581585 modulates the risk of diabetes and can be used as a promising tool for identifying high-risk individuals.

Genetic polymorphisms of apolipoprotein E in nonarteritic anterior ischemic optic neuropathy.

To elucidate the potential role of genetic polymorphisms of apolipoprotein E (APOE) in nonarteritic anterior ischemic optic neuropathy (NAION) and the association between APOE and NAION-induced ocular impairments. A total of 73 NAION patients and 73 sex- and age-matched healthy controls were recruited for the study. Genomic DNA was isolated from peripheral blood samples. The alleles and genotypes of APOE were explored. The interaction between APOE and medical comorbidities was assessed by the multifactor dimensionality reduction (MDR) method. Among 81 affected eyes of NAION patients, an additional association study of APOE isoforms with visual impairments was carried out. The allele and genotype frequencies for APOE showed significant differences when comparing NAION cases and controls. Multivariate analysis adjusted for age, sex, hypertension, dyslipidemia, diabetes mellitus, cardiovascular disease, and cerebrovascular disease revealed that the ε3/ε4 genotype (OR = 3.86, 95% CI = 1.13-13.25, p = 0.032) and ε4 allele (OR = 3.55, 95% CI = 1.05-11.99, p = 0.041) were strong independent risk factors for NAION. Compared to eyes with the ε3/ε3 + ε2/ε4 genotype, individuals with the ε4/ε4 + ε3/ε4 genotype had worse visual field defects (VFDs) and thinner macular ganglion cell complex (mGCC) thicknesses with larger focal loss of volume (FLV) and general loss of volume (GLV). Compared to ε4 noncarriers, ε4 carriers also tended to have more serious VFD and mGCC loss. APOE polymorphisms conferred a significant risk of NAION and were significantly related to ocular impairments caused by NAION.

Polymorphisms in DNA Repair and Xenobiotic Biotransformation Enzyme Genes and Lung Cancer Risk in Coal Mine Workers.

Background: Currently coal mining employs over 7 million miners globally. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons and radioactive radon, significantly increasing the risk of lung cancer (LC). The susceptibility for LC is modified by genetic variations in xenobiotic detoxification and DNA repair capacity. The aim of this study was to investigate the association between GSTM1 (deletion), APEX1 (rs1130409), XPD (rs13181) and NBS1 (rs1805794) gene polymorphisms and LC risk in patients who worked in coal mines. Methods: The study included 639 residents of the coal region of Western Siberia (Kemerovo region, Russia): 395 underground miners and 244 healthy men who do not work in industrial enterprises. Genotyping was performed using real-time and allele-specific PCR. Results: The results show that polymorphisms of APEX1 (recessive model: ORadj = 1.87; CI 95%: 1.01–3.48) and XPD (log additive model: ORadj = 2.25; CI 95%: 1.59–3.19) genes were associated with increased LC risk. GSTM1 large deletion l was linked with decreased risk of LC formation (ORadj = 0.59, CI 95%: 0.36–0.98). The multifactor dimensionality reduction method for 3-loci model of gene–gene interactions showed that the GSTM1 (large deletion)—APEX1 (rs1130409)—XPD (rs13181) model was related with a risk of LC development. Conclusions: The results of this study highlight an association between gene polymorphism combinations and LC risks in coal mine workers.

Association study of SNPs in LncRNA CDKN2B-AS1 with breast cancer susceptibility in Chinese Han population.

The study aimed to analysis the genetic variation of the lncRNA CDKN2B-AS1 SNPs, and explored the regulation of SNPs on the invasion and metastasis of Breast cancer (BC). The SNPs (Single Nucleotide Polymorphisms) was screened for genotyping among 504 Chinese Han patients and 505 controls, which were frequency-matched for age (±2 years). Logistic analysis was to explore the relationship between SNPs and the BC risk. Interactions between SNPs and reproductive factors was explored using the multifactor dimensionality reduction (MDR) method. qRT-PCR was conducted to detect the CDKN2B-AS1 expression in plasma of different rs10965215 and rs2518723 genotypes. The effect of rs10965215 A>G mutation on the binding ability of CDKN2B-AS1 and miR-4440 was verified by dual luciferase experiment. CCK-8, scratch and Transwell experiment were performed to explore the effect of miR-4440 over-expression on BC cell proliferation, migration and invasion. A total of 13 SNP was screened. The individuals with SNPs rs2518723C>T, rs10965215 A>G, rs77792598C>G, rs4977753 T>C, rs75917766C>T and rs78545330C>G mutations might increase the BC risk. MDR results revealed that individuals with rs10965215 G genotype who age at menarche≥13 and regardless of the number of abortion<2 or ≥2 had a higher risk of BC. The relative expression of CDKN2B-AS1 in rs10965215 homozygous wild AA genotype (8.88±3.43) was lower than heterozygous GA (11.08±2.90) and homozygous mutant GG genotype (11.31±2.90). When rs10965215 wild A genotype was carried, there was an interaction between CDKN2B-AS1 and miR-4440. The CCK-8, Transwell, and scratch experiment were all found that miR-4440 over-expression might enhance the proliferation, invasion and migration of BC cells. CDKN2B-AS1 gene polymorphism might be related to the susceptibility of BC, CDKN2B-AS1 rs10965215 A/G genotype probably affect the proliferation, invasion and migration of BC cells by modulating the interactions with of miR-4440.