ANALISIS POLIMORFISME PROMOTER GEN FEROPORTIN (FPN1) -1355G/C DAN STATUS BESIPADA REMAJA PUTRI PONDOK PESANTREN DI YOGYAKARTA

SRI WAHYUNI, dr. Arta Farmawati, Ph.D.

2015 | Tesis | S2 Ilmu Kedokteran Dasar dan Biomedis

Latar Belakang. Data WHO menyebutkan angka kejadian anemia pada wanita tidak hamil usia reproduktif di Indonesia adalah 33,1%, lebih tinggi daripada prevalensi anemia di dunia (30,2%). Feroportin (FPN1) adalah salah satu gen yang berperan penting dalam metabolisme besi yang mengkode protein feroportin untuk absorbsi, pelepasan dan daur ulang zat besi dalam tubuh. Varian di regio promoter gen FPN1 -1355G/C menyebabkan peningkatan ekspresi feroportin dan ekspor besi sehingga kebutuhan besi seluler meningkat, Hb dan kadar feritin serum menurun yang merupakan tanda anemia defisiensi besi. Tujuan. Mengkaji frekuensi polimorfisme gen FPN1 -1355G/C sebagai faktor risiko anemia desifiensi besi (ADB) pada remaja putri dan menilai status besi serta hubungan asupan zat besi dengan status besi remaja putri di Pondok Pesantren di Yogyakarta, Indonesia. Metode.Desain penelitian ini adalah case-control. Sampel darah diambil dari 20 subjek anemia dan 52 subjek tidak anemia. Kadar feritin serum diperiksa dengan metode ELISA. Genotip diperiksa dengan metode PCR-RFLP.Kadar feritin serum diperiksa dengan metode ELISA. Kadar besi serum diperiksa dengan metode kolorimetrik. Asupan zat besi diukur dengan menggunakan Food Record and Food Frequency Quesionairre. Variabel kategorik dianalisis dengan Chi- Squareatau Fisher’s exact tests. Korelasi antara asupan zat besi dan kadar feritin serum dan besi serum diuji dengan uji korelasi Pearson dan Spearman. Nilai p< 0,05 menunjukkan perbedaan bermakna. Hasil. Frekuensi genotip CC sebesar 38,5%, CG sebesar 53,8% dan GG sebesar 7,7% pada kelompok ADB.Frekuensi genotip CC sebesar 36,5%, CG sebesar 55,8% dan GG sebesar 7,7% pada kelompok kontrol.Odds Ratio (OR) subjek pembawa alel C untuk kejadian ADB sebesar 2,036 (CI 95%, 0,518-7,995, p= 0,249). Subjek pembawa alel C pada kelompok ADB mempunyai rerata kadar feritin serum (p=0,000) dan besi serumlebih rendah dibandingkan kelompok non- ADB(p=0,02). Tidak terdapat perbedaan bermakna kadar hemoglobin dan indeks eritrosit antar kelompok genotip. Tidak terdapat hubungan antara asupan zat besi dengan kadar feritin serum (r=-0,074, p=0,535), namun terdapat korelasi positif antara asupan zat besi dengan kadar besi serum (r=0,239, p=0,043). Kesimpulan.Studi ini menunjukkan bahwaalel C polimorfisme FPN1 -1355G/C merupakan faktor risiko terjadinya anemia defisiensi besi pada remaja putri.Asupan zat besi berkorelasi positif dengan kadar besi serum pada penelitian ini.

Background: According to WHO data, the incidence of anemia in non-pregnant women of reproductive age in Indonesia is 33.1%, that is higher than prevalence of anemia in the world (30.2%). Ferroportin (FPN1) is one of important gene in iron metabolism encodes ferroportin for iron absorption, release, and recycle inside the body. The variant of FPN1 -1355G/C in promoter region leads to increases of ferroportin expression and iron export, increases of cellular iron needs, decreases of hemoglobin and serum ferritin levels that manifest to iron deficiency anemia. Objectives. To investigate the frequency of FPN1 -1355G/C polymorphism as a risk factor of iron deficiency anemia (IDA) and to assess iron statusand iron intake among adolescent girls in Islamic Boarding School in Yogyakarta, Indonesia. Methods. In this case-control study, we enrolled 20 adolescent girls with IDA dan 52 healthy adolescent girls, and analyze their complete blood count, genotypes, and iron intake. Promoter FPN1-1355G/C genotypes were determined using PCRRFLP method. Serum ferritin levels were measured with ELISA. Serum iron levels were determined using colorimetric method. Iron intake was assessed by Food Records and Food Frequency Quesionairre.Categorical variables were analyzed by Chi-Square or Fisher’s exact tests. Correlation between iron intake and serum ferritin levels or serum iron levelswere calculated using Pearson dan Spearman correlation tests. A p-value < 0.05 was considered statistically significant. Results. Genotypes distribution were 38.5% for CC, 53.8% for CG, and 7.7% for GG in IDA group. The genotype frequencies were CC 36.5%, CG 55.8% and GG 7.7% in control group. The odds ratio (OR) of C allele having IDA was 2.036 (95% CI, 0.518-7.995, p=0.249). Subjectscarrying C allelle in IDA group had lower serum ferritin levels and serum iron levels than non-IDA group (p = 0.000 and p = 0.02, respectively). There was no significant difference in hemoglobin levels and erythrocyte indices between genotype groups. There was no significant correlation between iron intake and serum ferritin levels (r = -0.074, p = 0.535), but there was a significant correlation between iron intake and serum iron levels (r = 0.239, p = 0.043). Conclusions. Our study suggests that C allele of FPN1 -1355G/C genetic polymorphism is a risk factor for iron deficiency anemia among adolescent girls. There was a significant correlation between iron intake and serum iron levelsin this study.

Kata Kunci : Anemia defisiensi besi, polimorfisme FPN1 -1355G/C, kadar feritin serum, kadar besi serum, asupan zat besi