Pengaruh Polimorfisme NRG-1 rs35753505 C/T Terhadap Kadar Neuregulin 1 pada Neonatus Kurang Bulan Sesuai Masa Kehamilan

Abstract

Objective : Handling premature babies is still a challenge nowadays. The biggest challenge is how to reduce the risk of morbidity so that later it will reduce longterm morbidity so that premature babies can grow optimally. Neuregulin 1 (NRG- 1) acts as an endogenous protector in fetal development. Decreasing NRG-1 levels can interfere with surfactant formation in premature infants and affect several organs such as the heart, brain and nerves, and immune system. Methods : A cross-sectional study was conducted, enrolling 48 preterm neonates. Neonates with severe congenital anomaly were excluded. ELISA and PCR were performed to obtain NRG-1 level and polymorphism data, respectively. Short term morbidity was observed for 72 hours. Bivariate analysis was done with chi square, Fisher’s exact, Kruskal Wallis dan Mann-Whitney U tests. Multivariate analysis was performed using logistic regression test.Pvalue of <0,05 was considered significant at 95% confidence interval. Result : Subjects with T/T genotype had higher NRG-1 level compared to 2 other genotypes. Similar result was found in subjects with T allele compared to C allele. Subjects with C/C and C/T genotypes had higher risk of having short term morbidity (13,33 times (P=0,003) and 6,19 times (P=0,019), respectively) compared to subjects with T/T genotype. The presence of C allele would raise the risk of having short term morbidities as high as 4,04 times (P=0,001). Low NRG- 1 level might raise the risk of having short term morbidities at 7,53 times (P=0,008) if it appear together with NRG-1 gene polymorphism. Conclusion : This study shows that SNP of NRG-1 gene is related to NRG-1 level and short term morbidities. Neonates with C/C and C/T genotypes along with C allele are prone to have low NRG-1 level and short term morbidities.

Tujuan : Penanganan bayi prematur masih merupakan tantangan saat ini. Tantangan terbesar adalah bagaimana menurunkan risiko morbiditas sehingga nantinya akan menurunkan gangguan jangka panjang agar bayi prematur ini dapat tumbuh optimal. Neuregulin 1 (NRG-1) berperan sebagai protektor endogen dalam perkembangan fetus. Penurunan kadar NRG-1 dapat mengganggu pembentukan surfaktan pada bayi prematur dan memengaruhi beberapa organ seperti jantung, otak dan saraf, serta sistem imun.. Metode : Penelitian ini menggunakan desain potong lintang terhadap 48 neonatus kurang bulan. Neonatus dengan kelainan kongenital berat tidak diikutsertakan. Pemeriksaan ELISA dilakukan untuk menilai kadar NRG-1 dan PCR untuk menilai polimorfisme. Morbiditas jangka pendek dipantau selama 72 jam. Analisis bivariat dilakukan dengan uji chi square, Fisher’s exact, Kruskal Wallis dan Mann-Whitney U test. Analisis multivariat dilakukan dengan uji regresi logistik. Nilai P<0,05 dianggap bermakna pada interval kepercayaan 95%. Hasil : Subjek dengan genotipe TT memiliki kadar NRG-1 yang lebih tinggi dibandingkan 2 genotipe lainnya. Hal serupa dijumpai pada subjek dengan alel T dibandingkan dengan alel C. Subjek dengan genotipe C/C dan C/T lebih berisiko menderita morbiditas jangka pendek masing-masing sebesar 13,33 kali (P=0,003) dan 6,19 kali (P=0,019) dibandingkan subjek dengan genotipe TT. Keberadaan alel C akan meningkatkan risiko morbiditas jangka pendek sebesar 4,04 kali (P=0,001). Kadar NRG-1 yang rendah akan meningkatkan risiko morbiditas jangka pendek sebesar 7,53 kali (P=0,008) jika muncul bersama-sama dengan polimorfisme gen NRG-1. Kesimpulan : Penelitian ini menunjukkan bahwa SNP pada gen NRG-1 memengaruhi kadar NRG-1 dan morbiditas jangka pendek. Neonatus dengan genotipe C/C dan C/T serta alel C berisiko mengalami penurunan kadar NRG-1 dan peningkatan kejadian morbiditas jangka pendek.