Tag: Polymorphisms

Posted on

Genetic polymorphisms of the TNF-?-308G/A are associated with metabolic syndrome in asthmatic patients from Hebei province, China.

Related Articles

Genetic polymorphisms of the TNF-?-308G/A are associated with metabolic syndrome in asthmatic patients from Hebei province, China.

Int J Clin Exp Pathol. 2015;8(10):13739-46

Authors: Yang YH, Liu YQ, Zhang L, Li H, Li XB, Ouyang Q, Zhu GY

Abstract
Asthma is a complex inflammatory disease involving the critical actions of several important cytokines. Epidemiological data show that obesity could increase the risk of asthma, and insulin resistance, or metabolic syndrome are an important risk factor for obesity asthma. Some studies identified that upstream of the transcription start site within the TNF-? gene promoter region-308 polymorphism was associated insulin resistance or metabolic disorders, while this site was closely related to asthma. But no research was performed to evaluate the influence of TNF-?-308G/A polymorphism on metabolic syndrome in asthmatic patients. Here, we recruited 248 asthmatic patients, who were separated into asthma with Mets/asthma without Mets groups and 226 matched healthy controls from Hebei Province to evaluate the influence of TNF-?-308G/A polymorphism on metabolic syndrome in asthmatic patients. Single nucleotide polymorphism of TNF-?-308 locus was genotyped using PCR-RFLP. Some biochemical variables were also determined. Our result showed that the genotypic and allelic frequency of rs1800629 did not show significant difference between asthmatic patients and normal controls. However, the frequency of A allele was signi?cantly higher in asthma group with Mets (22.36%) than in controls (15.71%) (P = 0.02; OR = 0.647; 95% CI = 0.447-0.936). After analyzing the relationship between biochemical features of patients and genotype of TNF-?-308G/A, we found levels of LDL cholesterol, TNF-? and insulin, and HOMA-IR were significantly higher in the asthmatic patients carrying the GA and AA genotypes than in the carriers of GG genotype of rs1800629 (P = 0.029, P = 0.022, P = 0.043, respectively). Thus, our data suggested that TNF-?-308G/A variation was related to metabolic phenotype in asthma patients. Furthermore, we first identified TNF-?-308 A allele was the risk factor for asthmatic patients with Mets in Hebei population, China.

PMID: 26722602 [PubMed – in process]

View full post on pubmed: asthma

Posted on

Relation between sonic hedgehog pathway gene polymorphisms and basal cell carcinoma development in the Polish population.

Relation between sonic hedgehog pathway gene polymorphisms and basal cell carcinoma development in the Polish population.

Arch Dermatol Res. 2015 Nov 21;

Authors: Lesiak A, Sobolewska-Sztychny D, Majak P, Sobjanek M, Wodz K, Sygut KP, Majsterek I, Wozniacka A, Narbutt J

Abstract
In recent decades, increases have been observed in the incidence of nonmelanoma skin cancers, including basal cell carcinoma (BCC) and squamous cell carcinoma. BCC is the most common neoplasm in Caucasian populations. Sonic hedgehog (Shh) pathway impairment plays a key role in BCC pathogenesis, and there is evidence that Shh pathway genetic variations may predispose to BCC development. We genotyped 22 single-nucleotide polymorphisms (SNPs) in 4 Shh pathway genes: SHH, GLI, SMO, and PTCH. The study group consisted of 142 BCC patients and 142 age-matched, sex-matched healthy subjects (controls). SNPs were assessed using the PCR-RFLP method. The genotype distribution for the polymorphisms in the rs104894049 331 A/T SHH, rs104894040 349 T/C SHH, and rs41303402 385 G/A SMO genes differed significantly between the BCC patients and the controls. The presence of CC genotype in the SHH rs104894040 349 T/C polymorphism was linked to the highest risk of BCC development (OR 87.9, p < 0.001). Other genotypes, such as the TT in SHH rs104894049 331 A/T and the GG in SMO rs41303402 385 G/A also statistically raised the risk of BCC, but these associations were weaker. Other investigated polymorphisms showed no statistical differences between patients and controls. The results obtained testify to the importance of the SHH and SMO gene polymorphisms in skin cancerogenesis. These results mainly underline the potential role of SHH3 rs104894040 349 T/C gene polymorphism in the development of skin basal cell carcinomas in patients of Polish origin.

PMID: 26590974 [PubMed – as supplied by publisher]

View full post on pubmed: asthma

Posted on

Association between Dietary Patterns and Atopic Dermatitis in Relation to GSTM1 and GSTT1 Polymorphisms in Young Children.

Related Articles

Association between Dietary Patterns and Atopic Dermatitis in Relation to GSTM1 and GSTT1 Polymorphisms in Young Children.

Nutrients. 2015;7(11):9440-9452

Authors: Chung J, Kwon SO, Ahn H, Hwang H, Hong SJ, Oh SY

Abstract
Previous research suggests the association of glutathione S-transferase (GST) gene polymorphisms or diet, but no interactions between these factors in atopic dermatitis (AD). We conducted a community-based case-control study including 194 AD and 244 matched non-AD preschoolers. Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) present/null genotypes were evaluated uisng a multiplex PCR method. We measured dietary intakes by a validated food frequency questionnaire and constructed three dietary patterns such as “traditional healthy”, “animal foods”, and “sweets” diets. In stratified analyses by GST genotypes, the “traditional healthy” diet and reduced AD showed association only in the GSTM1-present group (odd ratio (OR) 0.31, 95% confidence interval (CI) 0.13-0.75). A similar pattern of the association existed in the combined GSTM1/T1 genotype that indicated the inverse association between the “traditional healthy” diet and AD in the double GSTM1/T1-present genotype group (OR 0.24, 95% CI 0.06-0.93). Results from the multiplicative test analyses showed that the “traditional healthy” diet on reduced AD was significant or borderline significant in the GSTM1-present group (OR 0.71, 95% CI 0.54-0.92 vs. GSTM1-null group) or the GSTM1/T1 double present group (OR 0.63, 95% CI 0.39-1.03 vs. GSTM1/T1 double null group). These findings demonstrate that the present type of GSTM1 may increase susceptibility to the potential effect of the “traditional healthy” diet on AD.

PMID: 26580648 [PubMed – as supplied by publisher]

View full post on pubmed: asthma

Posted on

Association Analysis Between FILIP1 Polymorphisms and Aspirin Hypersensitivity in Korean Asthmatics.

Related Articles

Association Analysis Between FILIP1 Polymorphisms and Aspirin Hypersensitivity in Korean Asthmatics.

Allergy Asthma Immunol Res. 2013 Jan;5(1):34-41

Authors: Kim JY, Kim JH, Park BL, Pasaje CF, Bae JS, Park JS, Jang AS, Uh ST, Kim YH, Kim MK, Choi IS, Cho SH, Choi BW, Park CS, Shin HD

Abstract
PURPOSE: Aspirin exacerbated respiratory disease (AERD) results in a severe asthma attack after aspirin ingestion in asthmatics. The filamin A interacting protein 1 (FILIP1) may play a crucial role in AERD pathogenesis by mediating T cell activation and membrane rearrangement. We investigated the association of FILIP1 variations with AERD and the fall rate of forced expiratory volume in one second (FEV1).
METHODS: A total of 34 common FILIP1 single nucleotide polymorphisms (SNPs) were genotyped in 592 Korean asthmatic subjects that included 163 AERD patients and 429 aspirin-tolerant asthma (ATA) controls.
RESULTS: This study found that 5 SNPs (P=0.006-0.01) and 2 haplotypes (P=0.01-0.03) of FILIP1 showed nominal signals; however, corrections for the multiple testing revealed no significant associations with the development of AERD (P(corr)>0.05). In addition, association analysis of the genetic variants with the fall rate of FEV1, an important diagnostic marker of AERD, revealed no significant evidence (P(corr)>0.05).
CONCLUSIONS: Although further replications and functional evaluations are needed, our preliminary findings suggest that genetic variants of FILIP1 might be not associated with the onset of AERD.

PMID: 23277876 [PubMed – in process]

View full post on pubmed: asthma

Posted on

Distribution of polymorphisms IL4-590 C/T and IL4 RP2 in the human populations of Madeira, Azores, Portugal, Cape Verde and Guinea-Bissau.

Related Articles

Distribution of polymorphisms IL4-590 C/T and IL4 RP2 in the human populations of Madeira, Azores, Portugal, Cape Verde and Guinea-Bissau.

Int J Mol Epidemiol Genet. 2012;3(2):179-83

Authors: Berenguer AG, C�¢mara RA, Brehm AD, Oliveira S, Fernandes AT

Abstract
The IL4 gene is located on chromosome 5q23.3-31.2. Polymorphisms within this cytokine gene, like the derivative allele T of IL4-590, have been reported as being associated to elevated IgE serum levels and asthma. In the present work, the allelic and genotypic frequency of the IL4-590 and IL4 RP2 polymorphisms was carried out in 599 individuals from Madeira, Azores, Portugal mainland, Cape Verde and Guinea-Bissau and in a sample of 101 asthmatics from Madeira population. In all populations the polymorphisms were in LD and presented a significant dissimilar allelic and genotypic distribution (p<0.05) except between mainland Portugal and Madeira when compared to Azores. Significant differences regarding both loci were found between Madeira population and the group of asthmatics. Genotype 183183TT frequency is higher for African populations while 253253CC prevails in Caucasian populations. The existence of a Hardy-Weinberg Disequilibrium in Guinea-Bissau population not observed in neutral markers leads to the hypothesis of natural selection occurring in these loci probably associated to a rapid population growth an hypothesis strengthened by neutral STRs D5S818 and CSF1PO gene diversity.

PMID: 22724055 [PubMed – in process]

View full post on pubmed: asthma

Posted on

Multiple Polymorphisms Affect Expression and Function of the Neuropeptide S Receptor (NPSR1).

Multiple Polymorphisms Affect Expression and Function of the Neuropeptide S Receptor (NPSR1).

PLoS One. 2011;6(12):e29523

Authors: Anedda F, Zucchelli M, Schepis D, Hellquist A, Corrado L, D’Alfonso S, Achour A, McInerney G, Bertorello A, Lördal M, Befrits R, Björk J, Bresso F, Törkvist L, Halfvarson J, Kere J, D’Amato M

Abstract
BACKGROUND: neuropeptide S (NPS) and its receptor NPSR1 act along the hypothalamic-pituitary-adrenal axis to modulate anxiety, fear responses, nociception and inflammation. The importance of the NPS-NPSR1 signaling pathway is highlighted by the observation that, in humans, NPSR1 polymorphism associates with asthma, inflammatory bowel disease, rheumatoid arthritis, panic disorders, and intermediate phenotypes of functional gastrointestinal disorders. Because of the genetic complexity at the NPSR1 locus, however, true causative variations remain to be identified, together with their specific effects on receptor expression or function. To gain insight into the mechanisms leading to NPSR1 disease-predisposing effects, we performed a thorough functional characterization of all NPSR1 promoter and coding SNPs commonly occurring in Caucasians (minor allele frequency >0.02).
PRINCIPAL FINDINGS: we identified one promoter SNP (rs2530547 [-103]) that significantly affects luciferase expression in gene reporter assays and NPSR1 mRNA levels in human leukocytes. We also detected quantitative differences in NPS-induced genome-wide transcriptional profiles and CRE-dependent luciferase activities associated with three NPSR1 non-synonymous SNPs (rs324981 [Ile107Asn], rs34705969 [Cys197Phe], rs727162 [Arg241Ser]), with a coding variant exhibiting a loss-of-function phenotype (197Phe). Potential mechanistic explanations were sought with molecular modelling and bioinformatics, and a pilot study of 2230 IBD cases and controls provided initial support to the hypothesis that different cis-combinations of these functional SNPs variably affect disease risk.
SIGNIFICANCE: these findings represent a first step to decipher NPSR1 locus complexity and its impact on several human conditions NPS antagonists have been recently described, and our results are of potential pharmacogenetic relevance.

PMID: 22216302 [PubMed – in process]

View full post on pubmed: asthma

Posted on

Relationship between air pollution, NFE2L2 gene polymorphisms and childhood asthma in a Hungarian population.

Relationship between air pollution, NFE2L2 gene polymorphisms and childhood asthma in a Hungarian population.

J Community Genet. 2011 Dec 30;

Authors: Ungvári I, Hadadi E, Virág V, Nagy A, Kiss A, Kalmár A, Zsigmond G, Semsei AF, Falus A, Szalai C

Abstract
Air pollution and subsequent increased oxidative stress have long been recognized as contributing factors for asthma phenotypes. Individual susceptibility to oxidative stress is determined by genetic variations of the antioxidant defence system. In this study, we analysed the association between environmental nitrogen dioxide (NO(2)) exposure and single nucleotide polymorphisms (SNP) in NFE2L2 and KEAP1 genes and their common impact on asthma risk. We genotyped 12 SNPs in a case-control study of 307 patients diagnosed with asthma and 344 controls. NO(2) concentration was collected from the period preceding the development of asthma symptoms. Multiple logistic regression was applied to evaluate the effects of the studied genetic variations on asthma outcomes in interaction with NO(2) exposure. Our data showed that genotypes of rs2588882 and rs6721961 in the regulatory regions of the NFE2L2 gene were inversely associated with infection-induced asthma (odds ratio (OR)?=?0.290, p?=?0.0015, and OR?=?0.437, p?=?0.007, respectively). Furthermore, case-only analyses revealed significant differences for these SNPs between asthma patients that lived in modestly or highly polluted environment (OR?=?0.43 (0.23-0.82), p?=?0.01, and OR?=?0.51, p?=?0.02, respectively, in a dominant model). In conclusion, our results throw some new light upon the impact of NFE2L2 polymorphisms on infection-induced asthma risk and their effect in gene-environment interactions.

PMID: 22207565 [PubMed – as supplied by publisher]

View full post on pubmed: asthma

Posted on

Beta-adrenergic receptor polymorphisms associated with length of ICU stay in pediatric status asthmaticus.

Beta-adrenergic receptor polymorphisms associated with length of ICU stay in pediatric status asthmaticus.

Pediatr Pulmonol. 2011 Sep 8;

Authors: Carroll CL, Sala KA, Zucker AR, Schramm CM

Abstract
BACKGROUND: During severe exacerbations, asthmatic children vary significantly in their response to high-dose continuous ?(2) -adrenergic receptor (ADR?(2) ) agonist therapy. Genetic polymorphisms have been identified within the ADR?(2) that may be functionally relevant, but few studies have been performed in this population. Our hypothesis was that genotypic differences are associated with magnitude of response to ADR?(2) agonist treatment during severe asthma exacerbations in children. METHODS: Children aged 2-18 years admitted to the ICU (intensive care unit) with a severe asthma exacerbation between 2006 and 2008 were eligible. Genotyping of the ADR?(2) was performed. RESULTS: Eighty-nine children consented and were enrolled. Despite similar clinical asthma scores on admission, children with the Gly(16) Gly genotype at amino acid position 16 had significantly shorter ICU length of stay (LOS) and hospital LOS, compared to children with Arg(16) Arg and Arg(16) Gly genotypes. Children with either the Gln(27) Glu or Glu(27) Glu genotype at amino acid position 27 also had significantly shorter ICU LOS and hospital LOS compared to children with the Gln(27) Gln genotype. The Arg(16) Gly-Gln(27) Gln haplotype was associated with the longest ICU LOS, but this was not statistically different from other haplotypes. CONCLUSIONS: In this cohort of children with severe asthma exacerbations, ADR?(2) polymorphisms were associated with responses to therapy. Knowledge of the genetic profile of children with asthma may allow for targeted therapy during acute exacerbations. Pediatr Pulmonol. © 2011 Wiley-Liss, Inc.

PMID: 21905268 [PubMed – as supplied by publisher]

View full post on pubmed: asthma