Association between DPP6 gene rs10260404 polymorphism and increased risk of sporadic amyotrophic lateral sclerosis (sALS): a meta-analysis

• Published in: Neurological sciences 2024-07, Vol.45 (7), p.3225-3243
• Main Authors: Miah, Mohammad Mohasin, Zinnia, Maliha Afroj, Tabassum, Nuzhat, Islam, Abul Bashar Mir Md. Khademul
• Format: Article
• Language: English
• Subjects: Alleles; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - epidemiology; Amyotrophic Lateral Sclerosis - genetics; Case-Control Studies; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases - genetics; Gene polymorphism; Genetic Predisposition to Disease - genetics; Humans; Medicine; Medicine & Public Health; Meta-analysis; Motor neurons; Nerve Tissue Proteins; Neurodegenerative diseases; Neurology; Neuroradiology; Neurosurgery; Original Article; Polymorphism; Polymorphism, Single Nucleotide; Potassium Channels; Psychiatry; Risk factors; Spinal cord
• ISSN: 1590-1874; 1590-3478; 1590-3478
• DOI: 10.1007/s10072-024-07401-2

Background Sporadic amyotrophic lateral sclerosis (sALS) is a severe neurodegenerative disease characterized by continuous diminution of motor neurons in the brain and spinal cord. Earlier studies indicated that the DPP6 gene variant has a role in the development of sALS. This meta-analysis was designed to uncover the role of rs10260404 polymorphism of the DPP6 gene and its association with sALS. Methods All case–control articles published prior to October 2022 on the association between DPP6 (rs10260404) polymorphism and sALS risk were systematically extracted from different databases which include PubMed, PubMed Central, and Google Scholar. Overall odds ratios (ORs) and “95% confidence intervals (CIs)” were summarized for various genetic models. Subgroup and heterogeneity assessments were performed. Egger’s and “Begg’s tests were applied to evaluate publication bias. Trial sequential analysis (TSA) and false-positive report probability (FPRP) were performed. Results Nine case–control studies containing 4202 sALS cases and 4444 healthy controls were included in the meta-analysis. A significant association of the DPP6 (rs10260404) variant with an increased sALS risk in overall pooled subjects under allelic model [C allele vs. T allele, OR = 1.149, 95% CI (1.010–1.307), p -value = 0.035], dominant model [CC + CT vs. TT, OR = 1.165, 95% CI (1.067–1.273), p -value = 0.001], and homozygote comparison [CC vs. TT, OR = 1.421, 95% CI (1.003–2.011), p -value = 0.048] were observed. Moreover, in subgroup analysis by nationality, remarkable associations were detected in Dutch, Irish, American, and Swedish under allelic, dominant, and homozygote models. Additionally, stratification analysis by ethnicity exhibited an association with sALS risk among Caucasians and Americans under different genetic models. Interestingly, none of the models found any significant association with Asians. Conclusion The present meta-analysis indicates that DPP6 (rs10260404) polymorphism could be a candidate risk factor for sALS predisposition.