Perubahan Metilasi DNA Akibat Paparan Timbal Perinatal Meningkatkan Resiko Terjadinya Gangguan Sistem Saraf : Narative Review

Anggraeni Janar Wulan, Irfannuddin Irfannuddin, Mohammad Zulkarnain, Nur Arfian

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ABSTRACT

 

Perinatal lead (Pb) exposure causes in DNA methylation patterns. Changes in methylation patterns have been shown to cause neurotoxicity due to Pb with inter- and transgenerational inheritance patterns. The inheritance of these patterns increases the risk of developmental programming for neurodegenerative diseases and impaired cognitive, emotional, mental, and motor function development. To analyze the effects of perinatal Pb exposure on changes in DNA methylation patterns, what genetic material is involved, possible nervous system disorders, and influencing factors.  Narrative Review using databases from (1) PubMed Central, (2) Google Scholar, (3) Nature, and (4) Cell Press. The articles used were published between 2014 and 2024. The keywords used were lead exposure, DNA methylation, and neurodevelopment combined with Boolean Operators (AND/OR). A total of 11 articles met the criteria and were analyzed narratively. Perinatal exposure to Pb causes changes in DNA methylation, both hypermethylation and hypomethylation. The changes were widespread in various body tissues, including neurons in the cerebral cortex, hippocampus, blood, and placenta, and were inherited by offspring in the F1, F2, and F3 generations. The inheritance pattern was influenced by the age of exposure, stage of pregnancy, sex, and composition involved in the lineage, as well as the exposure dose. Genes considered important predictors of cognitive, motor, behavioral, and emotional developmental disorders are the CCSER1 gene (cg02901723), the GCNT1 gene (CG18515027), and the TRAPPC6A gene (cg19703494). Other genes that undergo changes in DNA methylation patterns are Ankdd1b, Cdh24, APOA5, Dynein Cytoplasmic 1 Light Intermediate Chain 1 (Dync1li1), GOLPH3, DNHD1, Trhde, FABP4, GPR20, and NINJ2.Prenatal exposure to lead increases the risk of various nervous system disorders in the next generation through epigenetic mechanisms, particularly DNA methylation. Changes in DNA methylation in certain genes can be used as predictors of nervous system developmental disorders.

 

Keywords: Developmental Programming, DNA Methylation, Neurodevelopment, Perinatal, Lead.

 

ABSTRAK

 

Paparan timbal (Pb) periode perinatal menyebabkan perubahan pola metilasi DNA . Perubahan pola metilasi terbukti berperan menyebabkan neurotoksisitas akibat Pb dengan pola pewarisan  inter dan transgenerasi. Pewarisan pola ini meningkatkan resiko  munculnya developmental programming terhadap penyakit neurodegeneratif dan gangguan fungsi perkembangan fungsi kognitif, emosi, mental, dan motorik.   Untuk menganalisis bagaimana pengaruh paparan Pb periode perinatal terhadap perubahan pola metilasi DNA, material genetik apa saja yang terlibat, gangguan fungsi sistem saraf apa saja yang mungkin ditimbulkan serta faktor – faktor yang mempengaruhi.  Narative Review dengan menggunakan basis data yang berasal dari (1) PubMed Central, (2) Google Scholar, (3) Nature, dan (4) Cell press. Artikel yang digunakan adalah artikel yang terbit antara tahun 2014 – 2024. Kata kunci yang digunakan adalah  lead exposure, DNA methylation dan neurodevelopment yang digabungkan dengan Boolean Operator (AND/OR). Sebanyak 11 artikel memenuhi kriteria dan dianalisis secara naratif. Paparan Pb perinatal menyebabkan hipermetilasi dan hipometilasi DNA pada promotor, regio, maupun lokus CpGs secara spesifik. Perubahan pola tersebar pada berbagai jaringan tubuh meliputi neuron kortek cerebri, hippocampus, darah, dan plasenta serta menjadi pola yang menetap yang diwariskan pada keturunannya baik F1, F2, dan F3. Pola pewarisan dipengaruhi oleh usia paparan, tahapan usia kehamilan, jenis kelamin dan  komposisi jenis kelamin yang terlibat dalam garis keturunan serta dosis paparan. Gen yang dianggap berperan penting sebagai prediktor terjadinya gangguan perkembangan fungsi kognitif, motorik,   perilaku, dan emosi adalah  gen CCSER1 (cg02901723), gen GCNT1 (CG18515027), dan gen TRAPPC6A (cg19703494). Gen lain yang mengalami perubahan pola metilasi DNA  dan berhubungan dengan penyakit pada sistem saraf adalah Ankdd1b, Cdh24, APOA5, gen Dync1li1, GOLPH3, DNHD1, Trhde, FABP4, GPR20, dan  NINJ2. Paparan Pb periode perinatal meningkatan resiko terjadinya berbagai gangguan fungsi sistem saraf pada generasi berikutnya melalui mekanisme epigenetik khususnya metilasi DNA. Perubahan metilasi DNA pada gen tertentu dapat digunakan sebagai prediktor terjadinya gangguan perkembangan sistem saraf. 

 

Kata Kunci: Developmental Programming, Metilasi DNA, Neurodevelopment, Perinatal, Timbal.


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DOI: https://doi.org/10.33024/mahesa.v6i8.24101

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