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Role of ADRB2 gene polymorphism in asthma and response to beta2-agonists in Polish children

100%

Szczepankiewicz A., Breborowicz A., Sobkowiak P., Kramer L., Popiel A.

Journal of Applied Genetics

2009

vol. 50

issue 3

275-281

The aims of this study were: (1) to find associations of asthma with single-nucleotide polymorphisms (SNPs) within the ADRB2 gene: Arg16Gly, Gln27Glu,-1023 G/A, ?367 T/C,-47 C/T ; (2) to define linkage disequilibrium in the gene region, basing on the analyzed SNPs; and (3) to analyze the importance of ADRB2 polymorphism for response to bronchodilator drugs in children diagnosed with bronchial asthma. We compared 113 asthmatic children and 123 healthy subjects from the Polish population. Genotyping was performed by PCR-RFLP. We found an association of the A allele of ?1023A/G ADRB2 polymorphism with asthma (P = 0.024). No significant associations with other SNPs were detected. Moderate linkage was found between Gln27Glu and -47C/T polymorphisms in linkage disequilibrium analysis (D' = 0.85, r2 = 0.429, LOD = 31.97). No significant differences were found in haplotype frequencies in comparison to the control group, implicating that they are not associated with susceptibility to asthma in the analyzed population. There was no significant correlation between the analyzed SNPs of the ADRB2 gene and the response to beta2-agonists. This is the first report providing suggestive evidence for association of ?1023A/G ADRB2 polymorphism with an increased risk of asthma. The analyzed SNPs may not play a major role in response to beta2-agonists in asthmatic children.

A vitamin K epoxide reductase-oxidase complex gene polymorphism (?1639G>A) and interindividual variability in the dose-effect of vitamin K antagonists

100%

Stepien E., Branicka A., Ciesla-Dul M., Undas A.

Journal of Applied Genetics

2009

vol. 50

issue 4

399-403

A daily dose of vitamin K antagonists (VKAs) may vary and its range depends on various interrelated factors. Low responsiveness to VKA (defined as a failure to achieve a target international normalized ratio [INR]) is associated with polymorphisms of the vitamin K epoxide reductase-oxidase complex gene (VKORC1). A highly prevalent promoter single-nucleotide polymorphism (VKORC1-1639 G>A, rs17878363) impairs VKORC1 expression and determines the interindividual variability of the target INR. We studied 57 patients receiving oral anticoagulation, including 50 subjects treated with acenocoumarol (mean dose: 5.7+-2.3 mg/day) and 7 treated with warfarin (mean dose: 9.6+-4.2 mg/day). The indications for the use of oral anticoagulant therapy were as follows: deep-vein thrombosis (N = 23); pulmonary embolism (N = 20); arterial thrombosis (N = 5); stroke (N = 4); atrial fibrillation with transient ischemic attacks (N = 2), and history of multiple thromboembolic events (N = 3). Identification of the VKORC1 genomic variation was performed using DNA sequencing methods. The prevalence of the mutated allele (VKORC1 -1639A) was 41%. The VKORC1 -1639G allele carriers required a higher daily dose of acenocoumarol (5.9+-1.9 mg) than the noncarriers (4.1+-3.3 mg; P < 0.001). All of 5 low responders (who failed to achieve a target INR using standard dose requirements of VKAs) were homozygous for the 1639G allele. Low responders did not differ from good responders with respect to age, gender, and body mass index. Our findings suggest the potential benefits from pharmacogenetic testing, and provide evidence that the VKORC1 -1639 G>A gene polymorphism may explain at least in part the low responsiveness to acenocoumarol.

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2 Journal of Applied Genetics

2 2009

1 Branicka A.

1 Breborowicz A.

1 Ciesla-Dul M.

1 Kramer L.

1 Popiel A.

1 Sobkowiak P.

1 Stepien E.

1 Szczepankiewicz A.

1 Undas A.

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Role of ADRB2 gene polymorphism in asthma and response to beta2-agonists in Polish children

A vitamin K epoxide reductase-oxidase complex gene polymorphism (?1639G>A) and interindividual variability in the dose-effect of vitamin K antagonists