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RANKL Gene Polymorphism as a Potential Biomarker to Identify Acute Charcot Foot Among Indian Population With Type 2
A SaiPrathiba1, G Senthil1, Udyama Juttada1
1MV Hospital for Diabetes and Prof M. Viswanathan Diabetes Research Centre, Chennai, India.
The International Journal of Lower Extremity Wounds
|July 16, 2019
Summary
Investigating the Receptor Activator of Nuclear Factor kappa-B Ligand (RANKL) gene variants in an Indian population revealed significant associations with diabetic neuropathy and Charcot neuropathic osteoarthropathy (CN). These RANKL gene polymorphisms may serve as independent risk factors for CN development.
Area of Science:
- Genetics and Molecular Biology
- Endocrinology
- Diabetology
Background:
- Charcot neuropathic osteoarthropathy (CN) is a severe complication of diabetic neuropathy.
- Previous genetic studies on CN have primarily focused on the osteoprotegerin gene.
- The role of Receptor Activator of Nuclear Factor kappa-B Ligand (RANKL) gene variants in CN susceptibility remains underexplored.
Purpose of the Study:
- To investigate the association between RANKL gene variants and the susceptibility to diabetic neuropathy (DPN) and CN.
- To measure serum levels of soluble RANKL (sRANKL) in Indian patients with type 2 diabetes, DPN, and CN.
- To identify potential genetic risk factors for CN in the Indian population.
Main Methods:
- Genotyping of RANKL single nucleotide polymorphisms (SNPs) -643 C/T and -693 C/G using polymerase chain reaction-restriction fragment length polymorphism.
- Measurement of serum sRANKL levels via enzyme-linked immunosorbent assay (ELISA).
- Comparison of genotype frequencies and sRANKL levels among control, DPN, and DPN with CN groups.
Main Results:
- Serum sRANKL levels differed significantly across the three study groups.
- The "CT" genotype and "T" allele of RANKL -643 C/T were more prevalent in DPN and CN groups compared to controls.
- The "GG" genotype and "G" allele of RANKL -693 C/G were more frequent in DPN and CN groups versus controls.
- RANKL -643 C/T was associated with DPN, while -693 C/G was associated with both DPN and CN.
Conclusions:
- RANKL gene polymorphisms (-643 C/T and -693 C/G) are significantly associated with diabetic neuropathy and Charcot neuropathic osteoarthropathy in the Indian population.
- RANKL -693 C/G polymorphism may be an independent risk factor for the development of CN.
- Elevated sRANKL levels correlate with the progression of diabetic complications, including CN.
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