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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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