KEDOKTERAN
LAPORAN HASIL PENELITIAN HIBAH PENELITIAN TIM PASCASARJANA (HPTP) II
PERAN GEN PENYANDI RESEPTOR ADRENERGIK β-3 DAN ASUPAN MAKAN TERHADAP SINDROMA METABOLIK PADA REMAJA
Oleh: Prof.Dr.dr.H. Djanggan Sargowo, SpPD.,SpJP (K), FIHA,FACC,FCAPC, FESC Prof. Dr.dr.Edy Wijayanto, SpPK (K) Dra. Diana L.,PhD dr. Sri Andarini, MKes dr. Maharani Siti Nurul M., Ssi
Dibiayai Oleh Direktorat Jenderal Pendidikan Tinggi, Departemen Pendidikan Nasional, Melalui DIPA Universitas Brawijaya berdasarkan SK Rektor Nomor : 039/SK/2010, tanggal 17 Februari 2010
UNIVERSITAS BRAWIJAYA NOPEMBER 2010
RINGKASAN
Sindroma metabolik (SIMET) adalah suatu istilah untuk kelompok faktor resiko penyakit jantung dan tipe-2 diabetes mellitus (DM). Faktor resiko tersebut terdiri dari dislipidemia atherogenik, naiknya tekanan darah, naiknya plasma glukosa, keadaan protrombotik, dan keadaan pro-peradangan. Sindroma metabolik diprediksi menyebabkan kenaikan 2 kali lipat resiko terjadinya penyakit jantung dan 5 kali lipat pada penyakit DM tipe2. Meningkatnya angka kejadian SM terjadi akibat peningkatan kasus obesitas. Laporan dari National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) menunjukkan peningkatan prevalensi SM remaja dari periode 19881992 ke periode 1999-2000, yaitu dari 4,2% menjadi 6,4%. Prevalensi laki-laki yang mengalami SM ternyata lebih besar dibanding perempuan, yaitu 9,1% dibanding 3,7%. Remaja dengan Indek Masa Tubuh (IMT) persentil ke ≥95 32,1% mengalami SM, sedang yang mempunyai IMT antara persentil ke 85-95 didapatkan angka kejadian SM sebesar 7% (Duncan, 2004). Prevalensi SM pada remaja Cina Indonesia yang obesitas di Jakarta Utara dan Selatan sebesar 19,14% untuk laki-laki dan 10,63% untuk perempuan (Sibarani, 2006). Penelitian SM pada orang dewasa pernah dilakukan di Surabaya dengan menggunakan kriteria ATP III didapatkan prevalensi sebesar 32% (Tjokroprawiro,2007). Tujuan umum penelitian ini adalah menjelaskan pengaruh polimorfisme gen penyandi reseptor adrenergik b3 dan komposisi asupan makan remaja mempengaruhi timbulnya sindroma metabolik pada remaja?. Tujuan umum dicapai melalui beberapa tujuan khusus. · Menjelaskan pengaruh komposisi asupan makan terhadap komponen sindroma metabolik (adipocyte fatty acid binding protein (A-FABP) , adiponektin, Apo B100, GD 2 jam pp, GDP, HDL, IMT, LP, LDL, TD diastole, TD sistole, TG, Total Kolesterol) · Mengidentifikasi adanya polimorfisme gen penyandi reseptor adrenergik b3 pada remaja sindroma metabolik. · Menjelaskan hubungan polimorfisme gen penyandi reseptor adrenergik b3 dengan sindroma metabolik pada remaja · Menjelaskan hubungan komposisi asupan makan dengan polimorfisme gen penyandi reseptor adrenergik b3 pada remaja. Guna mencapai tujuan tersebut dilakukan penelitian menggunakan pendekatan epidemiologi molekuler dengan rancangan studi kasus kelola. Untuk mencari prevalensi obesitas pada remaja diambil 20 sekolah secara random dari 190 sekolah di kota Malang dengan rincian 10 sekolah SMP dan 10 sekolah SMA. Kriteria obesitas ditentukan melalui Indek Masa Tubuh (IMT) kemudian dipakai kriteri dari Center Disease of Control (CDC). Dari remaja yang obesitas ditentukan status sindroma metabolik dengan criteria International Diabetes Federation (IDF), yaitu meningkatnya kadar trigliserida, menurunnya kadar HDL serta lingkar pinggang > 80 cm untuk perempuan dan > 90 cm untuk laki-laki. Sampel diambil sebesar 150 remaja dengan rincian: 73 kelompok kasus sindroma metabolik dan 77 remaja kelompok kontrol bukan sindroma metabolik. Kriteria sampel diterima dalam penelitian ini adalah: remaja dengan umur 13-19 tahun pada saat dilakukan penelitian, dan bertempat tinggal di wilayah Malang Raya, remaja bukan penderita asma bronchiale (pengobatan dengan kortikosteroid), nephrotic syndrom, cushing syndrom pada saat dilakukan penelitian, tidak merokok, bersedia sebagai responden untuk diambil sampel darahnya dengan menandatangani persetujuan (inform consent) dari orang tua.
Hasil penelitian ini menunjukkan bahwa hampir semua variabel terdapat perbedaan bermakna antara responden yang mengalami SM dengan responden yang tidak SM (p<0,05) kecuali kadar gula darah puasa dan kadar gula darah 2 jam pp, karbohidrat yang dikonsumsi serta total kalori (p>0,05). Faktor komposisi asupan makan berpengaruh terhadap SM dengan nilai koefisien sebesar 0,563 (p<0,05). Selain itu menunjukkan bahwa total kolesterol sebagai indikator SM mempunyai nilai paling tinggi, selanjutnya diikuti oleh indikator LDL. Sedang untuk indikator komposisi asupan makanan yang mempunyai nilai paling tinggi adalah total kalori diikuti lemak selanjutnya karbohidrat, berarti asupan lemak lebih dominan pengaruhnya terhadap sindroma metabolik dibandingkan dengan asupan karbohidrat. Analisis lebih lanjut menunjukkan bahwa remaja dengan asupan makan tinggi lemak mempunyai kemungkinan untuk terkena SM 3,02 kali lebih besar dibandingkan dengan kelompok yang tidak. Dari hasil PCR dapat diidentifikasi gen lebih kurang pada base pair ke 250. Dari 21 sampel SM dan 9 tidak SM yang dianalisa, ditemukan 4 sampel dari kelompok SM yang mengalami polimorfisme (13,3%), yang menyebabkan perubahan asam amino atau terbentuknya kodon stop. Dari hasil analisis menunjukkan bahwa remaja yang mengalami polimorfisme gen penyandi reseptor adrenergik β3 mempunyai kemungkinan untuk terkena SM 4,4 kali lebih besar dibandingkan dengan kelompok yang tidak mengalami polimorfisme. Setelah dianalisis lebih lanjut dengan menggunakan uji t, didapatkan kelompok remaja yang mengalami polimorfisme gen penyandi reseptor adrenergik β3, asupan karbohidratnya lebih banyak dari pada kelompok yang tidak mengalami polimorfisme (p<0,05). Sedangkan rata-rata mengkonsumsi lemak dalam jumlah lebih sedikit dibanding dengan kelompok yang tidak mengalami polimorfisme (p>0,05). Kesimpulan dari penelitian tahap II ini adalah remaja yang mendapatkan asupan makan lebih banyak, terjadi sindroma metabolik semakin meningkat. Remaja yang mengalami sindroma metabolik asupan makan lebih banyak lemak dari pada karbohidrat. Telah teridentifikasi adanya polimorfisme sebanyak 4 pada remaja yang mengalami sindroma metabolik (13,3%). Ada hubungan antara polimorfisme gen penyandi reseptor adrenergik β3 dengan sindroma metabolik pada remaja. Remaja yang mempunyai gen penyandi reseptor adrenergik β3 telah mengalami polimorfisme, mempunyai resiko sindroma metabolik 4,4 kali lebih tinggi dari pada remaja yang gen penyandinya tidak mengalami polimorfisme. Remaja yang mempunyai gen penyandi reseptor adrenergik β3 telah mengalami polimorfisme, asupan makan lebih banyak karbohidrat dari pada remaja yang tidak mengalami polimorfisme. Sehingga disarankan adanya pengaturan diet yaitu dengan pembatasan asupan lemak, agar tidak terjadi sindroma metabolik. Perlu deteksi secara genetik adanya polimorfisme sebelum usia remaja.
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