Correlation Between ENPP1 Gene rs1044498 Polymorphism with the Risk of Type 2 Diabetes Mellitus: A Meta-analysis

As a common metabolic disease, type 2 diabetes mellitus (T2DM) is regulated by the ectoenzyme nucleotide pyrophosphatase phosphodiesterase 1 (ENPP1). A functional polymorphism of ENPP1 (rs1044498, K121Q) has been found to contribute to T2DM susceptibility. This study aims to analyze the combined association of ENPP1 rs1044498 polymorphism with T2DM risk. We searched for publications in databases from January 2010 to December 2023. Pooled association strength was analyzed using either a random-effects or fixed-effects model, and expressed as combined odds ratios (ORs) with 95% confidence intervals (CIs). Data analysis was performed by STAT 12.0. Due to high heterogeneity, a random-effects model was used for the calculation. In the total population, ENPP1 rs1044498 was evidently related to an increased susceptibility to T2DM under the following models: Q vs. K (OR = 1.405, 95% CI = 1.059-1.863), KQ + QQ vs. KK (OR = 1.475, 95% CI = 1.075-2.023), QQ vs. KK + KQ (OR = 2.355, 95% CI = 1.302-4.262), QQ vs. KK (OR = 3.096, 95% CI = 1.393-6.882) and KQ vs. KK (OR = 1.399, 95% CI = 1.038-1.885). In ethnic subgroups, rs1044498 was associated with T2DM risk in Asians under the following models: Q vs. K (OR = 1.480, 95% CI = 1.017-2.154), KQ + QQ vs. KK (OR = 1.578, 95% CI = 1.047-2.379), QQ vs. KK+ KQ (OR = 3.709, 95% CI = 1.727-7.967), QQ vs. KK (OR = 5.049, 95% CI = 1.784-16.397) and KQ vs. KK (OR = 1.478, 95% CI = 1.008-2.167). The distinct association between rs1044498 and T2DM risk was discovered in the diagnostic criteria not shown subgroup and plasma subgroup. This study demonstrated high sensitivity with minimal publication bias. The ENPP1 121Q allele is a risk factor for T2DM, particularly in the Asian population.