Gene polymorphism and diabetic foot ulcer

Excerpt:


J. Pharm. Pharmacogn. Res., vol. 12, no. 2, pp. 348-362, Mar-Apr 2024. DOI: https://doi.org/10.56499/jppres23.1790_12.2.348 Review Role of polymorphism in vitamin D receptor gene on diabetic foot ulcer: A systematic review and meta-analysis [Papel del polimorfismo del gen receptor de la vitamina D en la úlcera del pie diabético: Una revisión sistemática y meta-análisis] Saminan Saminan1, … Continue reading Gene polymorphism and diabetic foot ulcer

J. Pharm. Pharmacogn. Res., vol. 12, no. 2, pp. 348-362, Mar-Apr 2024.

DOI: https://doi.org/10.56499/jppres23.1790_12.2.348

Review

Role of polymorphism in vitamin D receptor gene on diabetic foot ulcer: A systematic review and meta-analysis

[Papel del polimorfismo del gen receptor de la vitamina D en la úlcera del pie diabético: Una revisión sistemática y meta-análisis]

Saminan Saminan1, Naufal Gusti2, Shakira Amirah3, Muhammad Iqhrammullah2*

1Department of Physiology, Faculty of Medicine, Universitas Syiah Kuala, Banda Aceh 23111, Indonesia.

2Postgraduate Program of Public Health, Universitas Muhammadiyah Aceh, Banda Aceh 23123, Indonesia.

3Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia.

*E-mail: m.iqhram@oia.unsyiah.ac.id

Abstract

Context: Once vitamin D is converted to its active form, the molecule binds to its receptor (VDR) and performs its function as a transcription factor in modulating immune response, inflammation cascade, and insulin signaling. Among diabetic individuals, these activities are thought to be correlated with foot ulceration. Gene polymorphisms could change the function of VDR, thereby affecting the development of foot ulceration among individuals with diabetes.

Aims: To construct evidence on the role of VDR gene variants or single nucleotide polymorphisms (SNPs) on diabetic foot ulcers.

Methods: Records reporting the distribution of genotypes and/or alleles among diabetic foot ulcer (DFU) patients and published until 10 March 2023 were retrieved from 12 major databases using predetermined keywords. The original research articles included in the study were assessed for reporting quality using the Newcastle Ottawa Scale. The quality of genotypic and allelic data was appraised by Hardy-Weinberg equilibrium (HWE). A quantitative analysis-based fixed-effects model was performed to estimate the proportion of genotype and allele frequencies among DFU patients.

Results: Three studies were included in the systematic review reporting the FokI (rs2228570), TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232) SNPs. Based on pooled estimates, among DFU patients CC, CT, and TT genotypes of VDR FokI SNPs had a prevalence of 45%, 43%, and 12%, respectively, without significant heterogeneity found in the reported data (p-Het<0.001; I2>0%). ApaI and FokI were associated with DFU, while no association in all genotypic and allelic models was found between TaqI or BsmI and DFU. CC genotype of BsmI and T allele of FokI was associated with oxidative stress (one of the underlying factors in DFU).

Conclusions: Certain genotypes and alleles of FokI and ApaI SNPs could act as the risk factor for foot ulceration among diabetic individuals. More high-quality studies are still needed to draw solid conclusions on the role of VDR SNPs among DFU patients.

Keywords: diabetic complications; diabetic foot; gene variants; vitamin D; vitamin D receptor.

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Resumen

Contexto: Una vez que la vitamina D se convierte en su forma activa, la molécula se une a su receptor (VDR) y desempeña su función como factor de transcripción en la modulación de la respuesta inmunitaria, la cascada de la inflamación y la señalización de la insulina. Entre los individuos diabéticos, se cree que estas actividades están correlacionadas con la ulceración del pie. Los polimorfismos genéticos podrían cambiar la función de VDR, afectando la aparición de úlceras en los pies de los diabéticos.

Objetivos: Construir evidencias sobre el papel de las variantes del gen VDR o polimorfismos de nucleótido único (SNPs) en las úlceras del pie diabético.

Métodos: Los registros que informan sobre la distribución de genotipos y/o alelos entre los pacientes con úlcera de pie diabético (UPD) y publicados hasta el 10 de marzo de 2023 se recuperaron de 12 bases de datos principales utilizando palabras clave predeterminadas. Se evaluó la calidad de los informes de los artículos de investigación originales incluidos en el estudio mediante la escala de Newcastle Ottawa. La calidad de los datos genotípicos y alélicos se evaluó mediante el equilibrio de Hardy-Weinberg (HWE). Se realizó un modelo de efectos fijos basado en el análisis cuantitativo para estimar la proporción de las frecuencias genotípicas y alélicas entre los pacientes con DFU.

Resultados: Se incluyeron tres estudios en la revisión sistemática que informaban sobre los SNP FokI (rs2228570), TaqI (rs731236), BsmI (rs1544410) y ApaI (rs7975232). Según las estimaciones agrupadas, entre los pacientes con DFU los genotipos CC, CT y TT de los SNP VDR FokI tenían una prevalencia del 45%, 43% y 12%, respectivamente, sin que se encontrara heterogeneidad significativa en los datos comunicados (p-Het<0,001; I2>0%). ApaI y FokI se asociaron con DFU, mientras que no se encontró asociación en todos los modelos genotípicos y alélicos entre TaqI o BsmI y DFU. El genotipo CC de BsmI y el alelo T de FokI se asociaron con el estrés oxidativo (uno de los factores subyacentes en el DFU).

Conclusiones: Ciertos genotipos y alelos de los SNP de FokI y ApaI podrían actuar como factor de riesgo de ulceración del pie entre los individuos diabéticos. Todavía se necesitan más estudios de alta calidad para extraer conclusiones sólidas sobre el papel de los SNP VDR entre los pacientes con DFU.

Palabras Clave: complicaciones diabéticas; pie diabético; variantes génicas; vitamina D; receptor de la vitamina D.

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Citation Format: Saminan S, Gusti N, Amirah S, Iqhrammullah M (2024) Role of polymorphism in vitamin D receptor gene on diabetic foot ulcer: A systematic review and meta-analysis. J Pharm Pharmacogn Res 12(2): 348–362. https://doi.org/10.56499/jppres23.1790_12.2.348
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