Department of Immunology, ICMR-National Institute for Research in Tuberculosis, Chennai, India.
Department of Immunology, ICMR-National Institute for Research in Tuberculosis, Chennai, India.
Gene. 2024 Nov 15;927:148679. doi: 10.1016/j.gene.2024.148679. Epub 2024 Jun 12.
Genetic factors are reported to be connected with tuberculosis (TB) infection. Studies have shown that genetic variations in genes involved in the vitamin D pathway influence the levels of vitamin D found in the bloodstream (serum). Cyp27b1 (1α-hydroxylase) is an enzyme that activates the synthesis of bioactive vitamin D by hydroxylation of 25(OH)DThe in vitro studies reported rare gene variants of Cyp27b1 such as rs118204011 and rs118204012, associated with loss of Cyp27b1 function and lower serum vitamin D levels. Globally, a critical gap exists in understanding the link between these gene variants with TB and vitamin D levels. Hence, the study objective is to comprehend the association of Cyp27b1 rs118204009 (G/A), rs118204011 (C/T), and rs118204012 (A/G) with tuberculosis susceptibility/protection and to assess the influence of gene variants on vitamin D levels in both healthy controls (HCs) and those with pulmonary tuberculosis (PTB) in South India.
Genomic DNA extraction was performed by salting-out procedure and subsequently genotyped through polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Vitamin D level was measured by Enzyme-Linked Immunosorbent Assay (ELISA).
In rs118204012 (A/G), a substantial association was found with PTB susceptibility in allele 'A' [Odds Ratio (OR): 1.52 (1.02-2.26); p = 0.044] and 'AA' genotype [OR: 1.69 (1.02-2.81); p = 0.040] through the dominant model. Allele 'G' [OR: 0.66 (0.44-0.98); p = 0.044) was found to be associated with protection against TB. Males were associated with increased susceptibility towards TB compared to females in the rs118204011 "CC" [OR: 3.94 (1.94-7.98); p = 0.002] and rs118204012 'AA' [OR: 4.57 (2.13-9.79); p = 0.0001] genotypes. Vitamin D insufficiency (<30 ng/ml) was more prevalent in PTB patients (66.67 %) with the rs118201012 'AA' genotype compared with healthy controls (57.14 %). This genotype was associated with disease susceptible odds ratio of 1.5.
Cyp27b1 rs118204012 'AA' genotype was found to have association with vitamin D insufficiency and TB susceptibility. In terms of gender, our findings suggest that male individuals are correlated with a higher TB risk. This suggest that the gene variants may be involved in the downstream processing of serum Vitamin D levels and its association with the disease.
遗传因素与结核病（TB）感染有关。研究表明，参与维生素 D 通路的基因的遗传变异会影响血液（血清）中维生素 D 的水平。Cyp27b1（1α-羟化酶）是一种通过羟化 25(OH)D 将其激活为生物活性维生素 D 的酶。体外研究报道了 Cyp27b1 的罕见基因变异，如 rs118204011 和 rs118204012，与 Cyp27b1 功能丧失和血清维生素 D 水平降低有关。在全球范围内，人们对这些基因变异与 TB 和维生素 D 水平之间的联系存在理解上的重大差距。因此，本研究旨在了解 Cyp27b1 rs118204009（G/A）、rs118204011（C/T）和 rs118204012（A/G）与结核病易感性/保护的相关性，并评估基因变异对印度南部健康对照者（HCs）和肺结核（PTB）患者维生素 D 水平的影响。
采用盐析法提取基因组 DNA，随后通过聚合酶链反应和限制性片段长度多态性（PCR-RFLP）方法进行基因分型。通过酶联免疫吸附试验（ELISA）测量维生素 D 水平。
在 rs118204012（A/G）中，等位基因“ A”[优势比（OR）：1.52（1.02-2.26）；p=0.044]和“ AA”基因型[OR：1.69（1.02-2.81）；p=0.040]与 PTB 易感性具有显著相关性，采用显性模型。等位基因“ G”[OR：0.66（0.44-0.98）；p=0.044]与 TB 保护有关。与女性相比，男性在 rs118204011“ CC”[OR：3.94（1.94-7.98）；p=0.002]和 rs118204012“ AA”[OR：4.57（2.13-9.79）；p=0.0001]基因型中与 TB 易感性增加有关。与健康对照组（57.14%）相比，rs118201012“ AA”基因型的 PTB 患者（66.67%）更易出现维生素 D 不足（<30ng/ml）。该基因型与疾病易感性的比值比为 1.5。
发现 Cyp27b1 rs118204012“ AA”基因型与维生素 D 不足和 TB 易感性有关。就性别而言，我们的研究结果表明，男性个体与更高的 TB 风险相关。这表明基因变异可能参与了血清维生素 D 水平的下游处理及其与疾病的关联。
