D Vitamini ve Genetik
Özet
Bu çalışma, insan vücudundaki D vitamini düzeylerini etkileyen genetik ve epigenetik faktörleri, ilgili genleri ve bu genlerdeki varyasyonların etkilerini incelemektedir. D vitamininin dolaşımdaki ana biyobelirteci olan 25-hidroksivitamin D3 (25(OH)D) seviyelerinin %20-80 oranında kalıtsal olduğu ikiz ve aile çalışmalarında gösterilmiştir. Genom çapında ilişkilendirme çalışmaları (GWAS), DBP/GC, NADSYN1/DHCR7, CYP2R1 ve CYP24A1 gibi önemli genlerin serum D vitamini konsantrasyonu ile ilişkili olduğunu ortaya koymuştur. Karaciğerde D vitaminini kalsidiole dönüştüren CYP2R1 genindeki mutasyonlar tip Ib raşitizme yol açarken, böbrekte aktif hormonal form olan kalsitriole dönüşümü sağlayan CYP27B1 genindeki kusurlar tip 1 raşitizme neden olur. D vitaminini taşıyan polimorfik DBP/GC proteinindeki rs4588 ve rs7041 varyasyonları ile aktif formun yıkımını sağlayan CYP24A1 genindeki mutasyonlar da kalsiyum dengesi ve D vitamini seviyelerini doğrudan etkiler. Ek olarak, SEC23A ve AMDHD1 gibi genlerin de bu yolağı düzenlemede rol oynayabileceği ileri sürülmektedir. Tüm bu veriler, hipovitaminoz D ve buna bağlı kalıtsal hastalıkların gelişiminde gen-çevre etkileşimlerinin kritik öneme sahip olduğunu göstermektedir.
This study examines the genetic and epigenetic factors affecting vitamin D levels in the human body, the related genes, and the impacts of variations within these genes. Twin and family studies have demonstrated that the levels of 25-hydroxyvitamin D3 (25(OH)D), the primary circulating biomarker of vitamin D, are inheritable at a rate of 20-80%. Genome-wide association studies (GWAS) have revealed that key genes such as DBP/GC, NADSYN1/DHCR7, CYP2R1, and CYP24A1 are associated with serum vitamin D concentrations. While mutations in the CYP2R1 gene, which converts vitamin D into calcidiol in the liver, lead to type Ib rickets, defects in the CYP27B1 gene, which enables conversion to the active hormonal form calcitriol in the kidney, cause type 1 rickets. The rs4588 and rs7041 variations in the polymorphic DBP/GC protein that transports vitamin D, along with mutations in the CYP24A1 gene responsible for degrading the active form, also directly affect calcium homeostasis and vitamin D levels. Additionally, genes like SEC23A and AMDHD1 are suggested to play roles in regulating this pathway. Consequently, all these data indicate that gene-environment interactions hold critical importance in the development of hypovitaminosis D and associated hereditary diseases.
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