ABSTRACT
Background: TfR2 plays an important role in iron regulation during red blood cells maturation and hepcidin production. Deficiency of iron intake depletes iron storages in the human body, which subsequently result in anemia. Pregnant women are one of the highest risk population that suffers iron deficiency anemia (IDA) because older gestational age has more blood dilution. Some studies have indicated that polymorphism of TfR2 gene decreases hepcidin levels in blood circulation, leading to iron overload. The aim of this study was to determine the correlation between frequency and type polymorphism of exon 4 TfR2 gene and incidence of iron deficiency anemia in pregnant women in Boyolali.
Methods: This observational analytic study was conducted in four primary health centers in Boyolali regency with cross sectional research design. Purposive sampling was used to recruit pregnant women who full filled research criteria. Anemia or IDA status was determined using Hb levels and red blood cells indexes with cyanmethemoglobin and routine hematology methods respectively. PCR and sequencing were performed to determine the TfR2 gene polymorphism. All sequencing data were analyzed by using a Bioedit software version 7.0,5. The independent student t test was used to compare average of Hb levels and red blood cells indexes between anemia and non anemia groups while the odd ratio test was used to analyze correlation between polymorphism and anemia or IDA.
Results: A total of 325 pregnant women were enrolled in this study. There are 68 pregnant women with anemia including 13 with IDA and others with non anemia. Four types of TfR2 gene polymorphism (A630T, T632C, C633G and C633T) were observed and T632C polymorphism was found in a majority of pregnant women. CC genotype is a risk factor for anemia (p = 0,973, OR 1,029) and a protective factor for IDA (p = 0,389, OR 0,313).
Conclusion: T632C is the most common polymorphism of exon 4 TfR2 gene and has different effects on anemia and IDA. Determination of ferritin, hepcidin and erythropoietin levels is required for confirming whether or not this polymorphism is associated with anemia or IDA.
Keywords: TfR2 gene, polymorphism, iron deficiency anemia, pregnant women, Boyolali
ABSTRAK
Latar Belakang: Reseptor transferin-2 (RTf2) berperan penting dalam regulasi besi baik dalam proses pematangan sel eritrosit maupun pengaturan hormon hepcidin. Kekurangan asupan besi akan menurunkan cadangan besi yang dapat menyebabkan anemia. Ibu hamil merupakan populasi tersering yang menderita  anemia defisiensi besi (ADB), dikarenakan terjadi pengenceran (dilusi) plasma darah seiring dengan pertambahan usia kehamilan. Ibu hamil sangat berpotensi mengalami anemia karena terjadi pengenceran (dilusi) plasma darah seiring dengan pertambahan usia kehamilan. Beberapa penelitian menunjukkan bahwa polimorfisme gen RTf2 mengakibatkan penurunan kadar hepcidin sehingga dapat menyebabkan kelebihan besi. Penelitian ini bertujuan untuk menganalisis hubungan antara frekuensi dan jenis polimorfisme gen RTf2 ekson 4 dengan kejadian ADB pada ibu hamil di Boyolali.
Metode: Desain penelitian adalah observasional analitik  dengan rancangan cross sectional yang dilakukan di empat puskesmas wilayah kabupaten Boyolali. Teknik pengambilan sampel dengan cara purposive sampling. Penentuan anemia dengan menggunakan metode cyanmethemoglobin dan penentuan ADB dengan menggunakan metode hematologi rutin. Polimorfisme gen RTf2 ekson 4 ditentukan dengan PCR dan dilanjutkan dengan sequencing. Hasil sequencing dianalisis dengan software Bioedit 7.0,5. Semua data diuji secara statistik. Perbedaan  rerata Hb dan indeks eritrosit menggunakan uji Independent T Test sedangkan hubungan antara polimorfisme dengan kejadian anemia atau ADB menggunakan  rasio odd.
Hasil: Dari 325 ibu hamil didapatkan 68 ibu hamil yang menderita anemia dan 13 diantaranya menderita ADB. Ada empat  jenis polimorfisme gen RTf2  ekson 4 yaitu: A630T, T632C, C633G, dan C633T. T632C merupakan jenis polimorfisme yang paling sering ditemukan pada subjek penelitian. Genotip CC merupakan faktor risiko terjadinya anemia (p=0,973, OR 1,029) dan merupakan faktor protektif terjadinya ADB (p=0,389, OR 0,313), meskipun hubungannya secara statistik tidak signifikan.
Kesimpulan: T632C merupakan jenis polimorfisme gen RTf2 ekson 4 yang paling sering ditemukan dan memberikan efek yang berbeda-beda pada anemia dan ADB. Pemeriksaan eritropoetin, ferritin dan hepcidin diperlukan untuk memastikan ada tidaknya hubungan antara polimorfisme gen RTf2 ekson 4 dengan anemia dan ADB.
Kata Kunci: Gen RTf2, Polimorfisme, Anemia Defisiensi Besi, Ibu Hamil, Boyolali