Polymorphic variants and risk of diabetic peripheral neuropathy in patients with type 2 diabetes mellitus: systematic review and meta-analysis

Background: Neuropathy is a frequent complication of diabetes mellitus, a disease that is growing exponentially worldwide. Genetic research has emerged as an important tool for better understanding its predisposition, although a systematic synthesis of existing evidence is needed to better comprehend its association. The objective of this review was to determine the association between polymorphic variants identified through massive genomic testing and the risk of peripheral diabetic neuropathy in patients with type 2 diabetes mellitus. Methods: Inclusion criteria were case-control, cohort, and cross-sectional studies examining polymorphic variants and diabetic neuropathy (DNP) risk in type 2 diabetes, studies using GWAS, EWAS, or microarray for identifying genetic polymorphisms, studies involving adults, and articles in English or Spanish. Exclusion criteria included case reports, case series, ecological studies, editor letters, reviews, or secondary studies and conference abstracts. Exhaustive search in PubMed, Scopus, and Web of Science databases, using keywords. Risk of bias was determined through Newcastle-Ottawa scale. A qualitative synthesis of the results was performed (frequency), including meta-analysis where applicable (forest plot and funnel plot). Results: The searching strategy identified 370 studies, from which 7 were chosen for the systematic review, included 9478 participants. The quality of the studies was mostly good, but a significant heterogeneity in methods was found. We identify a significant association between peripheral neuropathy and plenty of single nucleotide variants (SNVs). Just the SNV rs10555080 in the gene THEG5 showed a higher likelihood of neuropathy (OR:1,34; IC 95%: 1,19 − 1,49). Discussion: This study faced limitations due to heterogeneity in DNP definitions, genotyping methods, and a focus on white and Arab populations, limiting generalization. Only English and Spanish articles were included, potentially excluding relevant research in other languages. Multiple SNVs were identified through genomic testing that were associated with peripheral diabetic neuropathy in patients with type 2 diabetes mellitus; however, the SNVs were not similar between studies. Trial registration: This research received no funding and was registered in PROSPERO (ID CRD42024505256).