Analisis Peran Polimorfisme Gen CYP2R1 rs10741657, CYP27B1 rs10877012, Kadar Vitamin D pada Ibu Hamil Infeksi Laten Tuberkulosis terhadap Kadar Vitamin D, Katelisidin, Toll- Like Receptor 2, dan Interferon g pada Bayi Baru Lahir

Abstract

Background. Latent Tuberculosis Infection (LTBI) in pregnant women can progress to active TB infection and potentially infect their newborns such that infection-mediated immune responses may affect the child's immune system. The mechanism of immune system can be influenced by vitamin D levels. Low levels of vitamin D can play a role in the risk development of chronic infection diseases, and even malignancy; one of the aforementioned infections is the M. tuberculosis infection, so that on pregnant with LTBI are at a higher risk of developing into an active TB infection, especially if they are experiencing vitamin D deficiency. The vitamin D levels are affected by several vitamin D metabolism gene. The genetic variations of vitamin D metabolism gene, such as the CYP gene, plays a role in the first and second vitamin D hydroxylation pathway, in which this will affect the levels of vitamin D serum. We sought to determine the role of vitamin D in LTBI pregnant women and immune responses in neonates so as to preventative TB. Aim: Analyze the role of vitamin D metabolism gene polymorphism on vitamin D levels in LTBI pregnant women and the role of pregnant women’s vitamin D levels on their neonates immune system since newborns. Method: We used a case-control design which included 84 pregnant women in their third trimester and their neonates at three hospitals in Medan, North Sumatra. The study included 42 LTBI pregnant women as case group and 42 non-LTBI pregnant women as control group. Conducted from December 2021 to July 2022. The parameters that were assessed are the CYP2R1 rs10741657 and CYP27B1 rs10877012 gene polymorphism which then will be further correlated with the vitamin D levels on pregnant mothers and the LTBI incidence and then the vitamin D levels on pregnant mothers which will be further correlated with the newborn’s vitamin D levels, cathelicidin, IFNγ, and TLR2. Chi-squared and Fisher's tests were used for analyses, and Spearman's correlations were used for correlation testing. Result: This study also reported that there is not a significant correlation between CYP2R1 rs10741657 and CYP27B1 rs10877012 gene polymorphism and vitamin D levels (p = 0.541; p = 0.057) and the incidence of LTBI (p = 0.03; p = 0.001). LTBI pregnant women were at risk of vitamin D insufficiency (Odds Ratio (OR) = 3.667, p = 0.006) which influenced their newborn’s vitamin D levels (p = 0.038). Vitamin D levels in LTBI pregnant women and significantly correlated with the newborns’ TLR2 levels (p = 0.048). Normal vitamin D levels in newborns were significantly correlated with the newborns’ TLR2 levels (p = 0.005). The higher the vitamin D levels in the newborns’ of non-LTBI pregnant women influenced newborns’ cathelicidin (p = 0.043). Cathelicidin levels and IFNγ level in pregnant woman with LTBI influenced cathelicidin levels and IFNγ level in their newborns (p = 0,033; p = 0.001) Conclusion: The polymorphism of CYP2R1 rs10741657 and CYP27B1 rs10877012 does not play a role towards the incidence of LTBI and did not play a role towards the vitamin D levels on pregnant mothers with LTBI. Vitamin D levels in LTBI pregnant women influenced vitamin D levels in their newborns, which potentially impacted their immune response.