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

Mohammad Mohasin Miah; Maliha Afroj Zinnia; Nuzhat Tabassum; Abul Bashar Mir Md Khademul Islam

doi:10.1007/s10072-024-07401-2

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

Neurol Sci. 2024 Feb 21. doi: 10.1007/s10072-024-07401-2. Online ahead of print.

Authors

Mohammad Mohasin Miah¹, Maliha Afroj Zinnia¹, Nuzhat Tabassum¹, Abul Bashar Mir Md Khademul Islam²

Affiliations

¹ Department of Pharmacy, East West University, Dhaka, Bangladesh.
² Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka, 1000, Bangladesh. khademul@du.ac.bd.

PMID: 38381392
DOI: 10.1007/s10072-024-07401-2

Abstract

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.

Keywords: DPP6; Meta-analysis; Polymorphism; rs10260404; sALS.