Association of ADAM33 T1 Polymorphism With Subgroups of Pediatric Asthma Patients in Iran
Mir Reza GhaemiSara HemmatiArezou RezaeiMaryam SadrBahareh MohebbiHosseinali GhaffaripourNima RezaeiSeyed Alireza Mahdaviani
1
Citation
0
Reference
10
Related Paper
Citation Trend
Abstract:
There is strong evidence on the interaction of several genetic variations and environmental conditions in the etiology of asthma. Association of a disintegrin and metalloproteinase 33 (ADAM33) with asthma risk is not clear and shows diversity between nations and ethnicities. Several single nucleotide polymorphisms (SNP) of the ADAM33 gene are introduced and studied according to the disease onset and characteristics. The aim of our study is to determine the association of ADAM33 rs2280091 polymorphism and pediatric asthma in the Iranian population. A total of 63 asthma patients (aged 6-18) and 86 healthy controls were enrolled in our study. Asthma type, classification, and severity were defined. SNPs of the ADAM33 gene at rs2280091 (T1) were analyzed. Pulmonary function tests, total blood eosinophil count, and IgE count were also assessed. T1 genotype and allele frequencies were not associated with asthma risk in Iranian pediatric asthma. Atopic asthma subgroup and patients with normal eosinophil count showed association with ADAM33 rs2280091. Moreover, asthma patients with AG genotype showed lower pulmonary functions.Keywords:
Etiology
SNP
Abstract Risk classification for prostate cancer (PCa) aggressiveness and underlying mechanisms remain inadequate. Interactions between single nucleotide polymorphisms (SNPs) may provide a solution to fill these gaps. To identify SNP–SNP interactions in the four pathways (the angiogenesis-, mitochondria-, miRNA-, and androgen metabolism-related pathways) associated with PCa aggressiveness, we tested 8587 SNPs for 20,729 cases from the PCa consortium. We identified 3 KLK3 SNPs, and 1083 ( P < 3.5 × 10 –9 ) and 3145 ( P < 1 × 10 –5 ) SNP–SNP interaction pairs significantly associated with PCa aggressiveness. These SNP pairs associated with PCa aggressiveness were more significant than each of their constituent SNP individual effects. The majority (98.6%) of the 3145 pairs involved KLK3 . The 3 most common gene–gene interactions were KLK3-COL4A1:COL4A2 , KLK3-CDH13, and KLK3-TGFBR3. Predictions from the SNP interaction-based polygenic risk score based on 24 SNP pairs are promising. The prevalence of PCa aggressiveness was 49.8%, 21.9%, and 7.0% for the PCa cases from our cohort with the top 1%, middle 50%, and bottom 1% risk profiles. Potential biological functions of the identified KLK3 SNP–SNP interactions were supported by gene expression and protein–protein interaction results. Our findings suggest KLK3 SNP interactions may play an important role in PCa aggressiveness.
SNP
Tag SNP
Cite
Citations (12)
Background The molecular mechanism for the formation of the P 1 / P 2 blood groups remains unsolved. It has been shown that the P 1 / P 2 polymorphism is connected to the different A 4 GALT gene expression levels in P 1 and P 2 red blood cells. Study Design and Methods The present investigation conducted a pilot investigation that involved the detailed and stepwise screening of single‐nucleotide polymorphisms ( SNP s) in the A 4 GALT gene, followed by a larger‐scale association study. The transcription‐inducing activity by the different genotypes of SNP s was analyzed using reporter assays. Results A total of 416 different SNP sites in the A 4 GALT genes from four P 1 and four P 2 individuals were analyzed in the pilot investigation, and 11 SNP sites, distributed in the A 4 GALT I ntron 1 region, exhibited an association with the P 1 / P 2 phenotypes. In the follow‐up association study, the genotypes at the 11 SNP s of a total of 338 individuals across four different ethnic populations were determined, and the results show that two SNP s, rs2143918 and rs5751348, are consistently associated with the P 1 / P 2 phenotypes. Reporter assays demonstrated significantly higher transcription‐inducing activity by the SNP s bearing the P 1 ‐allele genotype than by the SNP s bearing the P 2 ‐allele genotype and that the difference in transcriptional activity was determined by the different genotypes at SNP rs5751348. Conclusion The results of this investigation demonstrate a consistent association of A 4 GALT SNPs rs2143918 and rs5751348 with the P 1 / P 2 phenotypes and suggest that SNP rs5751348 may lead to allelic variations in A 4 GALT gene expression and consequently leads to the formation of the P 1 / P 2 phenotypes.
SNP
Tag SNP
Genetic Association
Cite
Citations (21)
ORAI1 channels play an important role for breast cancer progression and metastasis. Previous studies indicated the strong correlation between breast cancer and individual single nucleotide polymorphisms (SNPs) of ORAI1 gene. However, the possible SNP-SNP interaction of ORAI1 gene was not investigated. To develop the complex analyses of SNP-SNP interaction, we propose a genetic algorithm (GA) to detect the model of breast cancer association between five SNPs (rs12320939, rs12313273, rs7135617, rs6486795 and rs712853) of ORAI1 gene. For individual SNPs, the differences between case and control groups in five SNPs of ORAI1 gene were not significant. In contrast, GA-generated SNP models show that 2-SNP (rs12320939-GT/rs6486795-CT), 3-SNP (rs12320939-GT/rs12313273-TT/rs6486795-TC), 5-SNP (rs12320939-GG/rs12313273-TC/rs7135617-TT/rs6486795-TT/rs712853-TT) have higher risks for breast cancer in terms of odds ratio analysis (1.357, 1.689, and 13.148, respectively). Taken together, the cumulative effects of SNPs of ORAI1 gene in breast cancer association study were well demonstrated in terms of GA-generated SNP models.
SNP
Tag SNP
SNP array
Cite
Citations (21)
The study of gene regulatory network and protein-protein interaction network is believed to be fundamental to the understanding of molecular processes and functions in systems biology. In this study, the authors are interested in single nucleotide polymorphism (SNP) level and construct SNP-SNP interaction network to understand genetic characters and pathogenetic mechanisms of complex diseases. The authors employ existing methods to mine, model and evaluate a SNP sub-network from SNP-SNP interactions. In the study, the authors employ the two SNP datasets: Parkinson disease and coronary artery disease to demonstrate the procedure of construction and analysis of SNP-SNP interaction networks. Experimental results are reported to demonstrate the procedure of construction and analysis of such SNP-SNP interaction networks can recover some existing biological results and related disease genes.
SNP
Tag SNP
SNP array
Cite
Citations (0)
Phenotype varies among the various types of Charcot Marie Tooth Neuropathies(CMT), However the problem arises in cases of same gene but gives a huge variety of phenotype in terms of early and late onset and severity of the disease. To check the impact of rs139723190 SNP on severity of the CMT 2k patients; being a genetic modifier of GDAP1. In the current study CMT 2k patients with early and late onset were analyzed for association of rs139723190 SNP in JPH1 gene responsible for CMT type severe and mild phenotypes. Single nucleotide polymorphisms (SNPs) lead to genetic differences in CMT patients on the basis of severity of the disease. The results of the present study suggest that variants of JPH1 may contribute to the genetic susceptibility as it plays a vital role as genetic modifier in CMT 2K. Candidates risk variants should be further evaluated in studies with a larger sample size.
SNP
Genetic Association
Genome-wide Association Study
Cite
Citations (4)
The hallmarks of pediatric acute respiratory failure (ARF) are dysregulated inflammation and surfactant dysfunction. The objective is to study association of surfactant protein (SP) genes' single nucleotide polymorphisms (SNPs) with ARF and its morbidity: pulmonary dysfunction at discharge (PDAD), employing a single-, two-, and three-SNP interaction model. We enrolled 468 newborn controls and 248 children aged ≤ 24 months with ARF; 86 developed PDAD. Using quantitative genetic principles, we tested the association of SP genes SNPs with ARF and PDAD. We observed a dominant effect of rs4715 of the SFTPC on ARF risk. In a three-SNP model, we found (a) 34 significant interactions among SNPs of SFTPA1, SFTPA2, and SFTPC associated with ARF (p = 0.000000002-0.05); 15 and 19 of those interactions were associated with increased and decreased risk for ARF, respectively; (b) intergenic SNP-SNP interactions of both hydrophobic and hydrophilic SP genes associated with PDAD (p = 0.00002-0.03). The majority of intra- and intergenic interactions associated with ARF involve the SFTPA2 SNPs, whereas most of the intra- and intergenic interactions associated with PDAD are of SFTPA1 SNPs. We also observed a dominant effect of haplotypes GG of SFTPA1 associated with increased and AA of SFTPC associated with decreased ARF risk (p = 0.02). To the best of our knowledge, this is the first study showing an association of complex interactions of SP genes with ARF and PDAD. Our data indicate that SP genes polymorphisms may contribute to ARF pathogenesis and subsequent PDAD and/or may serve as markers for disease susceptibility in healthy children.
SNP
Intergenic region
Pathogenesis
Genetic Association
Cite
Citations (15)
Background: Neonatal respiratory distress syndrome (RDS), due to surfactant deficiency in preterm infants, is the most common cause of respiratory morbidity. The surfactant proteins (SFTP) genetic variants have been well-studied in association with RDS; however, the impact of SNP-SNP (single nucleotide polymorphism) interactions on RDS has not been addressed. Therefore, this study utilizes a newer statistical model to determine the association of SFTP single SNP model and SNP-SNP interactions in a two and a three SNP interaction model with RDS susceptibility. Methods: This study used available genotype and clinical data in the Floros biobank at Penn State University. The patients consisted of 848 preterm infants, born <36 weeks of gestation, with 477 infants with RDS and 458 infants without RDS. Seventeen well-studied SFTPA1, SFTPA2, SFTPB, SFTPC, and SFTPD SNPs were investigated. Wang's statistical model was employed to test and identify significant associations in a case-control study. Results: Only the rs17886395 (C allele) of the SFTPA2 was associated with protection for RDS in a single-SNP model (Odd's Ratio 0.16, 95% CI 0.06-0.43, adjusted p = 0.03). The highest number of interactions (n = 27) in the three SNP interactions were among SFTPA1 and SFTPA2. The three SNP models showed intergenic and intragenic interactions among all SFTP SNPs except SFTPC. Conclusion: The single SNP model and SNP interactions using the two and three SNP interactions models identified SFTP-SNP associations with RDS. However, the large number of significant associations containing SFTPA1 and/or SFTPA2 SNPs point to the importance of SFTPA1 and SFTPA2 in RDS susceptibility.
SNP
Genetic Association
genetic model
Cite
Citations (9)
Surfactant proteins (SPs) are important for normal lung function and innate immunity of the lungs and their genes have been identified with significant genetic variability. Changes in quantity or quality of SPs due to genetic mutations or natural genetic variability may alter their functions and contribute to the host susceptibility for particular diseases. Alternatively, SP single nucleotide polymorphisms (SNPs) can serve as markers to identify disease risk or response to therapies, as shown for other genes in a number of other studies. In the current study, we evaluated associations of SFTP SNPs with idiopathic pulmonary fibrosis (IPF) by studying novel computational models where the epistatic effects (dominant, additive, recessive) of SNP-SNP interactions could be evaluated, and then compared the results with a previously published hypersensitivity pneumonitis (HP) study where the same novel models were used. Mexican Hispanic patients (IPF=84 & HP=75) and 194 healthy control individuals were evaluated. The goal was to identify SP SNPs and SNP-SNP interactions that associate with IPF as well as SNPs and interactions that may be unique to each of these interstitial diseases or common between them. We observed: 1) in terms of IPF, i) three single SFTPA1 SNPs to associate with decreased IPF risk, ii) three SFTPA1 haplotypes to associate with increased IPF risk, and iii) a number of three-SNP interactions to associate with IPF susceptibility. 2) Comparison of IPF and HP, i) three SFTPA1 and one SFTPB SNP associated with decreased risk in IPF but increased risk in HP, and one SFTPA1 SNP associated with decreased risk in both IPF and HP, ii) a number of three-SNP interactions with the same or different effect pattern associated with IPF and/or HP susceptibility, iii) one of the three-SNP interactions that involved SNPs of SFTPA1 , SFTPA2 , and SFTPD , with the same effect pattern, was associated with a disease-specific outcome, a decreased and increased risk in HP and IPF, respectively. This is the first study that compares the SP gene variants in these two phenotypically similar diseases. Our findings indicate that SNPs of all SFTPs may play an important role in the genetic susceptibility to IPF and HP. Importantly, IPF and HP share some SP genetic variants, suggesting common pathophysiological mechanisms and pathways regarding surfactant biogenesis, but also some differences, highlighting the diverse underlying pathogenic mechanisms between an inflammatory-driven fibrosis (HP) and an epithelial-driven fibrosis (IPF). Alternatively, the significant SNPs identified here, along with SNPs of other genes, could serve as markers to distinguish these two devastating diseases.
SNP
Hypersensitivity pneumonitis
Cite
Citations (9)
Carcass weight (CW) is one of the most important economic traits in pigs, directly affecting the income of farmers. In this study, a genome wide association study was performed to detect significant single nucleotide polymorphisms (SNPs) affecting CW in pigs derived from a $F_2$ intercross between Landrace and Korean native pig (KNP). Using high-density porcine SNP chips, highly significant SNPs were identified on SSC12. Two candidate genes, LOC100523510 and LOC100621652, were subsequently selected within this region and further investigated. Within these candidate genes, five SNPs were identified and genotyped using the VeraCode GoldenGate assay. The results revealed that one SNP in the LOC100621652 gene and four SNPs in the LOC100523510 gene are highly associated with CW. These SNP markers can thus have significant applications for improving CW in KNP. However, the functions of these candidate genes are not fully understood and require further study.
SNP
Candidate gene
SNP genotyping
SNP array
Tag SNP
Genome-wide Association Study
Cite
Citations (2)
1990年に開始されたヒトゲノムプロジェクトの結果，2004年10月にはヒトゲノムの99%を解読した信頼性（エラー率100,000塩基に1つ）の高い遺伝子配列が報告され，今まさにポストゲノムシークエンス時代に突入している．ゲノム研究は単一遺伝子疾患の原因遺伝子の解明から生活習慣病をはじめとする多因子病の疾患感受性遺伝子や薬物応答性に関する遺伝子の網羅的（ゲノムワイド）な遺伝子多型解析へ移りつつある．SNP（Single Nucleotide Polymorphism，一塩基遺伝子多型）はゲノム内に300-1500塩基に1個程度（約300万個）存在する．SNPは人種，個人により，遺伝子頻度が異なる場合が多いため，人種差，個人差を検出するための有効な遺伝子マーカーである．また，SNPそのものが疾病への感受性や薬物への反応性またその副作用の出現などに影響を与える場合もある．結果を信号化することができるため情報処理が容易であること，高速で大量にSNPをタイピングするための技術が実現していることから，網羅的遺伝子解析を行うにあたり便利である．この総説では，各種遺伝子多型と網羅的遺伝子多型解析に適したタイピング法，統計学的解析法とその限界，遺伝子解析研究の倫理的問題点について解説する．
SNP
Molecular Inversion Probe
SNP array
Tag SNP
Cite
Citations (0)