ANALISIS POLIMORFISME GEN FERROPORTIN (FPN1) Q248H DAN PROMOTER FPN1 -1355G/C PADA IBU HAMIL DENGAN ANEMIA DEFISIENSI BESI

NOR ISTIQOMAH, dr. Ahmad Hamim Sadewa

2013 | Tesis | S2 Ilmu Kedokteran Dasar dan Biomedis

Latar Belakang. Anemia defisiensi besi pada ibu hamil masih sering terjadi meski sudah banyak dilakukan pemeriksaan dan pelayanan kesehatan. Salah satu gen penting dalam metabolisme besi adalah FPN1 yang bertugas mensintesis protein ferroportin untuk absorpsi, release, dan recycle besi dalam tubuh. Beberapa variasi pada gen ini mempengaruhi fungsi dan ekspresiya. Adanya varian Q248H pada gen FPN1 mempengaruhi perubahan muatan negatif ke positif pada sekuen asam amino sehingga mempengaruhi ubikuitinasi dan degradasi. Variasi lainnya pada regio promoter FPN1 -1355G/C menyebabkan peningkatan ekspresi ferroportin dan ekspor besi, sehingga kebutuhan besi seluler meningkat, sTfR over ekspresi, Hb dan indeks eritrosit menurun, yang menunjukkan anemia defisiensi besi. Pada penelitian ini akan dipelajari frekuensi polimorfisme gen ferroportin Q248H dan -1355G/C pada ibu hamil dan kemungkinannya sebagai faktor risiko anemia defisiensi besi ibu hamil di Indonesia. Metode. Jenis penelitian ini analitik kategorik case-control. Sampel darah diambil dari 26 ibu hamil dengan anemia dan 48 ibu hamil tidak anemia. Pemeriksaan polimorfisme FPN1 Q248H dan -1355G/C menggunakan metode PCR-RFLP. Kadar soluble transferrin receptor (sTfR) dan hepcidin diukur denga metode ELISA. Kadar Hb, indeks eritrosit, sTfR, dan hepcidin kemudian dibandingkan antar kelompok genotip dengan uji t tidak berpasangan dan one way ANOVA. Nilai p<0,05 menunjukkan perbedaan bermakna. Hasil. Frekuensi polimorfisme FPN1 Q248H pada total subyek ibu hamil sebesar 0%. Frekuensi genotip polimorfisme promoter gen ferroportin -1355G/C pada ibu hamil yang menderita ADB sebesar 100%, sedangkan pada ibu hamil yang menderita anemia bukan karena defisiensi besi sebesar 95,2% (OR=1,600 p=0,710 95%CI 0,296-8,653). Rerata kadar Hb dan indeks eritrosit subyek yang membawaalel C lebih rendah daripada alel G, meskipun kadar Hb tidak berbeda bermakna secara statistik (p>0,05). Rerata kadar sTfR dan hepcidin subyek yang membawa alel C lebih tinggi daripada alel G (p<0,05), meskipun kadar hepcidin tidak berbeda bermakna secara statistik (p>0,05). Kesimpulan. Polimorfisme promoter FPN1 -1355 G/C merupakan faktor risiko terjadinya anemia defisiensi besi pada ibu hamil pada studi ini.

Background. Iron deficiency anemia in pregnancy remains an important health problem in Indonesia despite increase number of health promotion and services. Ferroportin (FPN1) is one of important gene in iron metabolism encodes ferroportin for iron absorption, release, and recycle inside the body. Several polymorphisms in this gene affect its function and expression. The polymorphism of FPN1 Q248H alters negative charge of the amino acid sequence positively, hence influenced its ubiquitination and degradation. The other varian, FPN1 - 1355G/C in promoter region, leads to increased of ferroportin expression and iron export, increased cellular iron needs, overexpression of sTfR, decrease Hb and erythrocyte indices that manifest to iron deficiency anemia. This research will study the frequency of ferroportin Q248H and -1355G/C polymorphism as a risk factor of iron deficiency anemia in pregnant women in Indonesia. Methods. The research design was a case and control study. Blood samples were taken from 26 pregnant women with anemia and 48 pregnant women without anemia. FPN1 Q248H and -1355G/C polymorphism were determined using PCR- RFLP method. Soluble transferrin receptor (sTfR) and hepcidin level were measured with ELISA. Haemoglobin, erythrocyte indices, sTfR, and hepcidin level were compared among genotype group, then statistically analyzed using independent sample t test and one way ANOVA. A p<0.05 was considered as significant. Results. There was no varian in FPN1 Q248H. However, we found FPN1 -1355G/C polymorphism with frequency in pregnant women with IDA and in pregnant women with anemia non IDA were 100% and 95.2%, respectively (OR=1.600 p=0.710 95%CI 0.296-8.653). The mean of Hb level and erythrocyte indices in subjects carrying C allele were lower than subjects carrying only G allele although Hb level is not significantly different (p>0.05). The sTfR and hepcidin level in subjects carrying C allele were higher than subjects carrying only G allele (p<0.05) although hepcidin level is not significantly different (p>0.05). Conclusions. In this study the FPN1 gene promoter -1355G/C polymorphism was a risk factor for iron deficiency anemia in pregnant women.

Kata Kunci : Polimorfisme gen FPN1 Q248H, polimorfisme promoter gen FPN1 -1355G/C, anemia defisiensi besi, hemoglobin, sTfR, hepcidin.