Cysteinyl Leukotrienes Pathway Genes, Atopic Asthma and Drug Response: From Population Isolates to Large Genome-Wide Association Studies.

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Cysteinyl Leukotrienes Pathway Genes, Atopic Asthma and Drug Response: From Population Isolates to Large Genome-Wide Association Studies.

Front Pharmacol. 2016;7:299

Authors: Thompson MD, Capra V, Clunes MT, Rovati GE, Stankova J, Maj MC, Duffy DL

Abstract
Genetic variants associated with asthma pathogenesis and altered response to drug therapy are discussed. Many studies implicate polymorphisms in genes encoding the enzymes responsible for leukotriene synthesis and intracellular signaling through activation of seven transmembrane domain receptors, such as the cysteinyl leukotriene 1 (CYSLTR1) and 2 (CYSLTR2) receptors. The leukotrienes are polyunsaturated lipoxygenated eicosatetraenoic acids that exhibit a wide range of pharmacological and physiological actions. Of the three enzymes involved in the formation of the leukotrienes, arachidonate 5 lipoxygenase 5 (ALOX5), leukotriene C4 synthase (LTC4S), and leukotriene hydrolase (LTA4H) are all polymorphic. These polymorphisms often result in variable production of the CysLTs (LTC4, LTD4, and LTE4) and LTB4. Variable number tandem repeat sequences located in the Sp1-binding motif within the promotor region of the ALOX5 gene are associated with leukotriene burden and bronchoconstriction independent of asthma risk. A 444A > C SNP polymorphism in the LTC4S gene, encoding an enzyme required for the formation of a glutathione adduct at the C-6 position of the arachidonic acid backbone, is associated with severe asthma and altered response to the CYSLTR1 receptor antagonist zafirlukast. Genetic variability in the CysLT pathway may contribute additively or synergistically to altered drug responses. The 601 A > G variant of the CYSLTR2 gene, encoding the Met201Val CYSLTR2 receptor variant, is associated with atopic asthma in the general European population, where it is present at a frequency of ?2.6%. The variant was originally found in the founder population of Tristan da Cunha, a remote island in the South Atlantic, in which the prevalence of atopy is approximately 45% and the prevalence of asthma is 36%. In vitro work showed that the atopy-associated Met201Val variant was inactivating with respect to ligand binding, Ca(2+) flux and inositol phosphate generation. In addition, the CYSLTR1 gene, located at Xq13-21.1, has been associated with atopic asthma. The activating Gly300Ser CYSLTR1 variant is discussed. In addition to genetic loci, risk for asthma may be influenced by environmental factors such as smoking. The contribution of CysLT pathway gene sequence variants to atopic asthma is discussed in the context of other genes and environmental influences known to influence asthma.

PMID: 27990118 [PubMed – in process]

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14% of UAE’s population suffers from asthma – gulfnews.com


Leicester Mercury

14% of UAE's population suffers from asthma
gulfnews.com
Asthma can be caused by a combination of genetic [inherited] factors and environmental factors. If you are prone to have asthma, getting exposed to dust, smoke and chemicals, to name a few, can trigger and aggravate asthma,” said Dr Jamal Mustafa
Guidance on how to cope with asthmaLeicester Mercury

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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]

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Improving chronic asthma management through population health – Brookings Institution (blog)


Brookings Institution (blog)

Improving chronic asthma management through population health
Brookings Institution (blog)
Asthma is a highly prevalent chronic condition that accounts for a large portion of medical expenditures, but effective control for high-risk patients often requires intensive education and home-environmental assessment of indoor air issues. Asthma

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Practice Fusion and AstraZeneca Partner on Population Health Management … – PR Newswire (press release)

Practice Fusion and AstraZeneca Partner on Population Health Management
PR Newswire (press release)
The program, developed by Practice Fusion and sponsored by AstraZeneca, identifies patients whose current asthma or COPD care does not meet evidence-based clinical guidelines, and then alerts physicians at the point of care via patient charts within
Aseptika secures US patent for its innovative respiratory infection testCambridge News

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Caesarean Section and Hospitalization for Respiratory Syncytial Virus Infection: A Population Based Study.

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Caesarean Section and Hospitalization for Respiratory Syncytial Virus Infection: A Population Based Study.

Pediatr Infect Dis J. 2014 Sep 17;

Authors: Kristensen K, Fisker N, Haerskjold A, Ravn H, Simões EA, Stensballe L

Abstract
BACKGROUND AND OBJECTIVE:: Hospitalization for respiratory syncytial virus (RSV) infection and asthma share common determinants, and meta-analyses indicate that children delivered by caesarean section (CS) are at increased risk of asthma. We aimed to investigate whether birth by CS is associated with an increased risk of hospitalization for RSV illness.
METHODS:: This was a population based national register based cohort study, conducted between January 1997 and June 2003, that included all children born in Denmark and all hospitalizations for RSV disease in them from 0 – 23 months of age. We used Cox regression with adjustment for prematurity, asphyxia, birth weight, multiple births, single parenthood, maternal smoking during pregnancy, older siblings, and asthma diagnoses up to 2 weeks before hospitalization for RSV infection, to compare the effects of acute or elective CS versus vaginal delivery, on subsequent hospitalization for RSV disease. A test for homogeneity was used to assess for effect over time.
RESULTS:: 399,175 children with 10,758 hospitalizations for RSV illness were included. 31,715 were born by acute CS and 30,965 by elective CS. Adjusted hazard ratios for hospitalization for RSV infection in children born by acute CS and by elective CS were 1.09 (1.01 – 1.17) and 1.27 (1.19 – 1.36), respectively. The effect of elective CS remained unchanged throughout the first two years of life (p = 0.53), whereas the effect of acute CS was only present in the second year of life (p = 0.001).
CONCLUSION:: Delivery by caesarian section is associated with an increased risk of hospitalization for RSV infeciton. This effect continues at least throughout the first two years of life.

PMID: 25232778 [PubMed – as supplied by publisher]

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