The role of K121Q ENPP1 polymorphism in diabetes mellitus and its complications

Abstract

The aim of the present study was to analyze the frequency of K121Q polymorphism in the ENPP1 gene of Brazilian subjects according to ethnic origin and to determine its possible association with diabetes mellitus (DM) and/or diabetic complications. A cross-sectional study was conducted on 1027 type 2 DM patients and 240 anonymous blood donors (BD). Ethnicity was classified based on self-report of European and African descent. The Q allele frequency was increased in African descendant type 2 DM patients (KK = 25.9%, KQ = 48.2%, and QQ = 25.9%) and BD (KK = 22.0%, KQ = 53.8%, and QQ = 24.2%) compared to European descendant type 2 DM patients (KK = 62.7%, KQ = 33.3%, and QQ = 4.1%) and BD (KK = 61.0%, KQ = 35.6%, and QQ = 3.4%). However, there was no difference in genotype distribution or Q allele frequency between diabetic and non-diabetic subjects (European descendants: DM = 0.21 vs BD = 0.21, P = 0.966, and African descendants: DM = 0.50 vs BD = 0.51, P = 0.899). In addition, there were no differences in clinical, laboratory or insulin resistance indices among the three genotypes. The prevalence of DM complications was also similar. In conclusion, K121Q polymorphism is more common among Afro-Brazilian descendants regardless of glycemic status or insulin sensitivity indices. Likewise, insulin sensitivity and DM chronic complications appear not to be related to the polymorphism in this sample.

Association of the ENPP1 K121Q polymorphism with susceptibility to type 2 diabetes in different populations: evidence based on 40 studies

“…Meyre et al [10] included subjects from two regions, Abate et al [24] included subjects from three regions, Bacci et al [25] included subjects from two regions, Lyon et al [31] included subjects from seven regions and C.B.leitao et al [36] included subjects from two regions. Thus, a total of fifty-one comparisons for the ENPP1 K121Q polymorphism.…”

Association between the ENPP1 K121Q Polymorphism and Risk of Diabetic Kidney Disease: A Systematic Review and Meta-Analysis

“…The study reported by Leitão et al . [ 10 ] was subdivided into two studies because it analyzed the ENPP1 polymorphism in two different populations.…”

“…[ 18 ] subdivided cases into two groups, proteinuric and end-stage renal disease (ESRD), while Leitão et al . [ 10 ] and De Cosmo et al . [ 20 ] defined DKD patients as microalbuminuric or macroalbuminuric.…”

“…Environmental factors such as hyperglycemia, arterial hypertension and/or dyslipidemia are known to play a key role in the development of DKD in genetically susceptible subjects [ 5 , 6 , 8 , 9 ]. Therefore, extensive efforts have been made to identify which genes are related to DKD; however, results are still inconclusive due to several genes being associated with small effects in different populations [ 10 , 11 , 12 , 13 ]. The identification of such genes will help detect individuals at high risk of developing DKD, and might provide a better understanding of its pathophysiology [ 14 ].…”

The association of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) K121Q gene polymorphism with the risk of type 2 diabetes mellitus in European, American, and African populations: a meta-analysis

“…The ENPP1 is a promising candidate gene for T2DM because it inhibits autophosphorylation of IR and impairs insulin signaling downstream of IR (12). A study found that the 121Q variant had a greater inhibitory action on IR compared to the 121K variant (13 (20) showed that the ENPP1 K121Q gene polymorphism was associated with increased risk of T2DM. Whereas several other studies (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) showed that the ENPP1 K121Q gene polymorphism had no significant association with increased risk of T2DM.…”