Department of Pediatrics, Ege University Hospital, Bornova, Izmir, 35100, Turkey.
Department of Pediatrics, Division of Neonatology, Ege University Hospital, Bornova, Izmir, 35100, Turkey.
Pediatr Res. 2023 Jul;94(1):275-279. doi: 10.1038/s41390-022-02426-9. Epub 2023 Jan 3.
Vitamin D and its receptor (VDR) effects on the gastrointestinal system are among its most critical multisystemic effects.
This study aimed to reveal that VDR gene polymorphisms may constitute a risk factor for necrotizing enterocolitis (NEC). VDR Fok1-Bsm1-Apa single-nucleotide polymorphisms were analyzed in the NEC group (n = 74) and the control group (n = 147). Among 1112 babies at and below 36 weeks of gestational age who were hospitalized between January 2013 and December 2016 with a diagnosis of prematurity, 74 of a total of 148 patients who developed NEC during follow-up (NEC group) were included in the study. When NEC was diagnosed according to clinical and radiological findings and staged using Modified Bell criteria, 9 (12.1%) of 74 babies were stage 1A, 13 (17.5%) stage 1B, and 5 (6.7%) stage 2A, 33 (44.5%) stage 2B, 7 (9.4%) stage 3A, 7 (9.4%) stage 3B. Of 964 babies who did not develop NEC during follow-up, 147 were included as the control group in the study. Genotyping of VDR polymorphisms was assayed by real-time PCR. From 221 premature babies in the NEC and control groups, 2 ml peripheral blood was taken appropriately and meticulously into an EDTA tube. DNA was isolated from these blood samples. DNA amplification was performed using a thermal cycler (Applied Biosystems GeneAmp PCR System 9600).
When the two groups were compared in terms of the prevalence of VDR Fok1 C/T genotype, it was found that TT genotype increased the risk of NEC by 2.697 times, and there was a significant relationship between TT genotype and the risk of NEC (p = 0.041). Multivariable logistic regression analysis was performed in terms of gestational age, birth weight, VDR gene polymorphism data between NEC and the control group. According to the analysis results, TT polymorphism, increased the risk of disease 4.5 times (p = 0.033).
Fok 1 C > T polymorphism in the VDR gene plays a role in the development of NEC. Identifying the risk groups by detecting gene polymorphisms that cause increased susceptibility to NEC may assist in the follow-up of these patients and in making early treatment decisions for them.
In this study examining the non-bone effects of the genetic differences in vitamin D metabolism in premature babies, Fok 1 polymorphism has been observed to be an essential risk factor for NEC. This is the first study in our country that has investigated the relationship between VDR gene polymorphism and necrotizing enterocolitis among the Turkish population. Identifying the risk groups by detecting gene polymorphisms that cause increased susceptibility to NEC may assist in the monitoring of these patients and in making early treatment decisions for them.
维生素 D 及其受体 (VDR) 对胃肠道的作用是其最重要的多系统作用之一。
本研究旨在揭示 VDR 基因多态性可能是坏死性小肠结肠炎 (NEC) 的一个危险因素。分析了 NEC 组（n=74）和对照组（n=147）中 VDR Fok1-Bsm1-Apa 单核苷酸多态性。在 2013 年 1 月至 2016 年 12 月期间因早产住院且胎龄在 36 周及以下的 1112 名婴儿中，共纳入了 148 名在随访期间发生 NEC 的患儿（NEC 组）。根据临床和影像学表现以及改良 Bell 标准进行 NEC 诊断，并根据改良 Bell 标准进行分期，74 名患儿中 9 名（12.1%）为 1A 期，13 名（17.5%）为 1B 期，5 名（6.7%）为 2A 期，33 名（44.5%）为 2B 期，7 名（9.4%）为 3A 期，7 名（9.4%）为 3B 期。在随访期间未发生 NEC 的 964 名患儿中，纳入了 147 名作为研究对照组。采用实时 PCR 检测 VDR 多态性的基因分型。从 NEC 和对照组的 221 名早产儿中，适当、细致地抽取 2ml 外周血到 EDTA 管中。从这些血液样本中提取 DNA。使用热循环仪（Applied Biosystems GeneAmp PCR System 9600）进行 DNA 扩增。
比较两组 VDR Fok1 C/T 基因型的患病率时，发现 TT 基因型使 NEC 的发病风险增加了 2.697 倍，TT 基因型与 NEC 发病风险之间存在显著关系（p=0.041）。对 NEC 组和对照组的胎龄、出生体重、VDR 基因多态性数据进行了多变量逻辑回归分析。根据分析结果，TT 多态性使疾病的发病风险增加了 4.5 倍（p=0.033）。
VDR 基因 Fok1 C＞＞T 多态性在 NEC 的发生发展中起作用。通过检测导致对 NEC 易感性增加的基因多态性，确定风险组，可能有助于对这些患者的随访，并为他们做出早期治疗决策。
在这项研究中，我们研究了维生素 D 代谢遗传差异对早产儿的非骨骼影响，观察到 Fok1 多态性是 NEC 的一个重要危险因素。这是我们国家首次研究 VDR 基因多态性与土耳其人群中坏死性小肠结肠炎的关系。通过检测导致对 NEC 易感性增加的基因多态性，确定风险组，可能有助于对这些患者的随访，并为他们做出早期治疗决策。
