POLIMORFISME GEN TRANS MEMBRANE PROTEASE SERIN 6 (TMPRSS6) SEBAGAI FAKTOR RISIKO ANEMIA DEFISIENSI BESI PADA IBU HAMIL

YULIANA HERI SUSELO, dr. Ahmad Hamim Sadewa, Ph.D

2013 | Tesis | S2 Ilmu Kedokteran Dasar dan Biomedis

Latar Belakang. Gen TMPRSS6 dilaporkan berperan pada homeostasis zat besi di dalam tubuh. Mutasi gen ini menyebabkan perubahan struktur dan fungsi enzim matriptase-2 yang mengakibatkan peningkatan kadar hepcidin di sirkulasi sehingga menghambat absorbsi zat besi di usus halus, pelepasan simpanan besi di liver dan daur ulang zat besi di makrofag. Beberapa polimorfisme gen TMPRSS6 termasuk Single Nucleotide Polymorphism (SNP) rs855791 (C2207T) berhubungan erat dengan anemia defisiensi besi (ADB), penurunan Hb dan indeks eritrosit serta peningkatan hepcidin serum. Penelitian ini bertujuan untuk mengetahui frekuensi SNP rs855791 gen TMPRSS6 yang kemungkinan sebagai salah satu faktor risiko terjadinya ADB pada ibu hamil di Indonesia. Metode. Jenis penelitian ini adalah observasional analitik case control. Populasi sampel adalah ibu hamil di wilayah Surakarta yang memenuhi kriteria inklusi dan eksklusi. Didapatkan 67 subyek terdiri dari 25 subyek anemia dan 42 subyek tidak anemia. Subyek anemia terdiri dari 7 subyek ADB dan 18 subyek anemia selain ADB. Semua subyek dilakukan pemeriksaan kadar Hb dan indeks eritrosit dilanjutkan deteksi rs855791 menggunakan teknik PCR-ARMS dan sekuensing serta ELISA untuk deteksi hepcidin serum. . Hubungan antara polimorfisme dan risiko ADB dianalisis dengan uji chi-square dan odds ratio. Perbedaan kadar Hb, indeks eritrosit dan hepcidin antar genotip dianalisis dengan independent t-test. Nilai p<0,05 menunjukkan perbedaan signifikan secara statistik. Hasil. Didapatkan SNP rs855791 baik yang bersifat homozigot maupun heterozigot dengan frekuensi subyek mutan (membawa alel T) pada ADB = 64,3% dan anemia selain ADB = 44,4%. Pada studi ini alel T pada rs855791 merupakan faktor risiko terjadinya ADB (p= 0,208, OR =2,250, 95% CI 0,628- 8,057). Rerata indeks eritrosit pada subyek dengan genotip yang membawa alel T lebih rendah dibandingkan subyek yang hanya membawa alel C saja meskipun tidak bermakna secara statistik (p>0,05). Rerata hepcidin serum pada subyek dengan genotip yang membawa alel T lebih tinggi dibandingkan subyek yang hanya membawa alel C saja tetapi tidak bermakna (p>0,05). Kesimpulan. Pada studi ini polimorfisme rs855791 gen TMPRSS6 merupakan faktor risiko terjadinya anemia defisiensi besi. Genotip dengan alel T mempengaruhi peningkatan hepcidin serum dan berdampak terhadap penurunan indeks eritrosit sebagai parameter ADB.

Backgrounds. TMPRSS6 gene was reported to have an important role in iron homeostasis in the body. Mutations of this gene lead to changes in the structure and function of matriptase-2 enzyme resulting in increase levels of hepcidin in circulation that inhibits iron absorption in the small intestine, the release of iron deposits in the liver and iron recycling in macrophages. Several polymorphisms of TMPRSS6 including single nucleotide polymorphism (SNP) rs855791 (C2207T) closely associated with iron deficiency anemia (IDA), decreased hemoglobin level and erythrocyte indices and increased serum hepcidin. This study aimed to determine the relationship of SNP rs855791 of TMPRSS6 and IDA in pregnant women in Indonesia. Methods. This study was an observational analytic case control. Sample population were pregnant women in the region of Surakarta who met inclusion and exclusion criteria. Sixty seven subjects were recruited as samples consist of 25 subjects with anemia and 42 subjects non anemia. Subjects with anemia consist of 7 subjects with IDA and 18 anemia without IDA subjects. All subjects were examined for hemoglobin and erythrocyte indices, polymorphism rs855791 detection using PCR-ARMS and sequencing, and ELISA for detection of serum hepcidin level. Chi square test and odds ratio models were used to evaluate the association between polymorphism and IDA risk. Independent t-test was used to determine the difference of Hb, erythrocyte indices and hepcidin among genotype. A p value < 0.05 considered as significant different. Results. SNP rs855791 was detected in all subjects which are both homozygous and heterozygous. Frequency of subject carrying T allele was high (IDA = 64.3% and anemia non IDA = 44.4%). In this study rs855791 was a risk factor for IDA (p = 0.208, OR =2.250, 95% CI 0.628-8.057). The mean erythrocyte indices in subjects carrying the T allele was lower than subjects carrying only C allele although not statistically significant (p>0.05). The mean serum hepcidin in subjects carrying T allele was higher than subjects carrying only C allele but not statistically significant (p>0.05). Conclusions. In this study the rs855791 polymorphism of TMPRSS6 gene is a risk factor for iron deficiency anemia. The T allele lead to increased serum hepcidin and decreased erythrocyte indices as IDA parameters.

Kata Kunci : anemia defisiensi besi, polimorfisme rs855791 gen TMPRSS6, hepcidin serum.