Investigating the Impact of ENPP1 Gene's K121Q (RS1044498) Polymorphism in Type 2 Diabetes via an Updated Meta-Analysis

Abstract

Type 2 Diabetes Mellitus (T2DM) occurs due to a complex relationship of genetic, environmental, and physiological factors, encompassing insufficient pancreatic insulin synthesis, peripheral insulin resistance, and diverse molecular pathways. The transmembrane glycoprotein ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) plays a role in insulin regulation, with the K121Q (rs1044498) variant on the ENPP1 gene being a subject of extensive study due to its potential association with T2DM. To comprehensively evaluate this relationship, a meta-analysis was conducted, pooling data from 48 studies retrieved from databases such as PubMed, Google Scholar, Science Direct, and Medline. The analysis, performed using Review Manager Version 5.4.1 and Stata version 14.1, included a total of 24,979 T2DM cases and 33,005 controls. Employing fixed-effects or random-effects models, the combined Odds Ratio (OR) and 95% Confidence Intervals (CIs) were calculated to quantify the connection's magnitude. In the overall population, all genotypic models revealed a statistically noteworthy connotation between ENPP1 and T2DM (P < 0.05). Notably, the homozygous model exhibited an OR of 1.53 (95% CI = 1.23-1.90, P = 0.0001), while the heterozygous, dominant, recessive, and allelic models showed ORs of 1.22 (95% CI = 1.08-1.37, P = 0.001), 1.15 (95% CI = 1.11-1.41, P = 0.0003), 1.38 (95% CI = 1.17-1.64, P = 0.0002), and 1.22 (95% CI = 1.10-1.36, P = 0.0003), correspondingly. Subgroup analysis by population indicated no significant correlation between the K121Q polymorphism and T2DM in the African population, while a noteworthy association was detected in both Asian and Caucasian populations, with the heterozygous model lacking significance in the latter. Despite no evidence of publication bias, a notable amount of residual heterogeneity among studies was identified. Sensitivity analysis established the steadiness and dependability of the meta-analysis findings, underscoring the complex nature of the ENPP1 gene's involvement in T2DM across diverse populations.