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22- ADRENERGIC RECEPTO- ADRENERGIC RECEPTORGENETIC POLYMORPHISMSGENETIC POLYMORPHISMS
DAN RESPONDAN RESPON
BROCHODILATOR SHORTBROCHODILATOR SHORTTERMTERM
Chest 2007;132;1485-1492
Jurnal Reading
Dr. YUNITA EKA WATI
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2-Agonist brochodilator
PendahuluanPendahuluan
Terapi obstruksi air
COPD, Asthma
Keterbatasan
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Bronchodilator respon (BDR) :salbutamol
PendahuluanPendahuluan
Continous phenotipe
pasien bervariasi luas
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COPD reversibel obstruksi airway >>
PendahuluanPendahuluan
Memperkirakan FEV1 dan
survival
Efek klinikOutcome klinikSurvival
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Respon terapi 2-Agonist ditentukan :
PendahuluanPendahuluan
Baseline airflowlimitation
Merokok
Umur genetik
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PendahuluanPendahuluan
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Illustration of ligand-biased signaling for the
2-Adrenergic Receptor.
PendahuluanPendahuluan
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Kromosom Manusia
PendahuluanPendahuluan
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PendahuluanPendahuluan
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PendahuluanPendahuluan
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SNP (Single NucleotideSNP (Single NucleotidePolymorphism)Polymorphism)
A SNP represents a variation of one base in the DNA. The nucleotide observed is different from the usualat this position. Each individual has many single nucleotide polymorphisms that together create aunique DNA arrangement for that individual. SNPs are usually thought to be point mutations that havebeen evolutionarily successful enough to be present in a significant proportion of the population. Thischange can be in coding regions or not, with or without consequence over the sequence of amino-acidand with or without influence on the structure of the protein. But in all the cases, SNPs representessential tools in Genetics and Genomic research.
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Respon fisiologis 2AR pada airway :
PendahuluanPendahuluan
Bronchodilator
Anti inflamasi Mucisiliar clearance Vascular endothelial permeability
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Peran ADR2 gene :
PendahuluanPendahuluan
Regular respon dari exogen
Hilangnya bronchoproteksi Pengaruh down-regulator Aktifasi signal-regulasi kinase Meningkatkan citokine expresi
Signal untuk cholinergic reseptorkontrol kontraktilitas airway
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Coding region ADR2 gene
PendahuluanPendahuluan
Codon 16 dan 27 Penelitian intensive ?
Arg16Glypolymorphism
Short termBDR pada 2-agonis
AsthmaAsthma
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PendahuluanPendahuluan
penelitian cohort ?
Arg16Gly, Gln27Glu
polymorphism
Short term
BDR pada 2-agonisSalbutamol
COPDCOPD
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Subyek Penelitian
Bahan dan MetodaBahan dan Metoda
274 pasien rawat jalan dengan COPDHokkaido University Hospital Sapporo JapanDiagnosa COPD oleh dokter paru
(respiratory physicians)Kriteria Inklusi :GOLD guideline40 tahun >>
PerokokRiwayat merokok > 10 pak per tahunIjin komite etik pemerintahInform consent
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Test Fungsi paru
Bahan dan MetodaBahan dan Metoda
Spirometer : FVC,FEV1, perkiraan FEV1 persent
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Genotyping DNA
Bahan dan MetodaBahan dan Metoda
Assay combining kinetic real time quantitative polymerasechain reaction with allele-spesific amplication
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Analisa Statistik
Bahan dan MetodaBahan dan Metoda
Linier regresi short term BDR + merokok pada COPD
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HasilHasil
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HasilHasil
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HasilHasil
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HasilHasil
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DiskusiDiskusi
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TERIMAKASIHTERIMAKASIH
TERIMAKASIHTERIMAKASIHTERIMAKASIHTERIMAKASIHTERIMAKASIHTERIMAKASIHTERIMAKASIHTERIMAKASIHTERIMAKASIHTERIMAKASIH
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