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Abstract
VDR GENE VARIANTS AND GUT MICROBIOME DIVERSITY IN RELATION TO VITAMIN D DEFICIENCY AND METABOLIC SYNDROME IN IRAQI ADULTS
*Asmaa Ghafer, Duaa Mohammed Al-Atta, Sura Talal Kadhim
ABSTRACT
Background: Metabolic syndrome (MetS) prevalence is increasing all over the world, with the Middle Eastern communities being no exception. Although metabolic disorders have been attributed to vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms, their interaction with gut microbiome modifications among Iraqi adults is insufficiently described. Objective: To investigate associations between VDR gene polymorphisms, gut microbiome diversity, and vitamin D status in relation to MetS among Iraqi adults. Methods: This case-control study enrolled 200 participants (100 MetS patients, 100 healthy controls) at Baghdad Teaching Hospital from January-August 2025. Serum 25-hydroxyvitamin D levels were measured by ELISA. Four VDR polymorphisms (FokI, BsmI, TaqI, ApaI) were genotyped using PCR-RFLP. Gut microbiome diversity was assessed through 16S rRNA sequencing, calculating Shannon diversity index and Prevotella/Bacteroides ratio. Multivariable logistic regression identified independent MetS predictors. Results: Vitamin D deficiency affected 70% of MetS patients versus 35% of controls (p<0.001). Mean serum 25(OH)D was significantly lower in MetS patients (17.2±6.8 vs 25.4±7.5 ng/mL, p<0.001). VDR FokI ff, BsmI bb, and ApaI aa genotypes were more prevalent in MetS patients. Gut microbiome diversity was significantly reduced in MetS patients (Shannon index: 3.2±0.6 vs 3.8±0.5, p<0.001). Independent MetS predictors included VDR FokI ff genotype (OR=1.9, 95%CI:1.1-3.4, p=0.02), vitamin D deficiency (OR=2.7, 95%CI:1.6-4.5, p<0.001), and low microbiome diversity (OR=2.2, 95%CI:1.3-3.7, p=0.003). Conclusion: Vitamin D deficiency, specific VDR polymorphisms, and reduced gut microbiome diversity are independently associated with MetS in Iraqi adults. These findings indicate the presence of multifactorial pathophysiology and indicate the importance of population-wide screening of vitamin D, genetic testing, and microbiome-specific interventions in this high-risk group.
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