Association of genetic polymorphism of PC‐1 gene (rs1044498 Lys121Gln) with insulin‐resistant type 2 diabetes mellitus in Punjabi Population of Pakistan

Abstract

Background Insulin resistance (IR), known to reduce the response to insulin action, develops with obesity leading to type 2 diabetes mellitus (T2DM). The PC‐1 gene has been associated with dyslipidemia, polycystic ovarian disease and T2DM in different regions of the world. The objective of the present study was to investigate the genetic association of PC‐1 rs1044498 polymorphism with insulin resistance in type 2 diabetes in the Punjabi population of Pakistan. Methods This study was carried out on 161 healthy controls and 161 patients of T2DM with insulin resistance. Whole blood was collected for DNA extraction and molecular studies. PCR‐RFLP with AvaII was performed to determine the genotype in cases and controls. Chi‐square and Hardy Weinberg analyses were carried out. Statistical analysis was performed by SPSS software. Results The demographic data of cases and controls showed significant differences for different parameters like glucose, insulin, Homeostatic model assessment‐insulin resistance (HOMA‐IR) and lipid profiles (p < 0.000). Different statistical models revealed that all the dominant models were found associated in between alleles for disease risk (p < 0.001) while no association of PC‐1 rs1044498 (K121Q) polymorphism was found with insulin‐resistant parameters in T2DM cases. Conclusion Overall, the results indicate that the K121Q polymorphism was not found associated with insulin resistance in type 2 diabetes in a Pakistani Punjabi population. This is the first‐ever report about the genotype of PC‐1 gene in this population.

Insulin resistance and the PC-1 gene sequence (ENPP1) (rs1044498) in people with Diabetes mellitus type- 2

“…Research done in China also revealed that T2DM or any of the characteristics of the metabolic syndrome have no correlation with PC-1 K121Q polymorphotype distribution (Daoming et al, 2006). The present findings differed from those of Abdo Albegali et al (2019), who found a correlation between PC-1 and the incidence of type 2 diabetes in the Punjabi population of Pakistan. While other studies have showed no link of this allele with illness risk (Rasmussen et al, 2000), prior research has demonstrated a correlation between the Q allele of PC1 (rs1044498) and insulin resistance (Gu et al, 2000).…”

Ultra-performance liquid chromatography-mass spectrometry-based metabolomics reveals Huangqiliuyi decoction attenuates abnormal metabolism as a novel therapeutic opportunity for type 2 diabetes

“…It was suggested that the incremental increase in PC in liver-derived microsomes in vitro or the extra PC level in the membrane restrains calcium homeostasis in organelles regulated by the calcium transport activity of sarcoendoplasmic reticulum Ca 2+ -ATPase (SERCA), which results in protein misfolding and endoplasmic reticulum (ER) stress, and nally stimulates insulin resistance. 96,97 HQLYD validly reduced the contents of PC(18:1(9Z)/15:0), PC(15:0/20:3(8Z,11Z, 14Z)) and PE(14:0/24:1(15Z)) by regulating glycerophospholipid metabolism and glycosylphosphatidylinositol(GPI)-anchor biosynthesis. D-glucose exists in the blood, spinal uid and lymph of animals, and is used as a nutrient for diuretic, detoxication and cardiotonic.…”

Current Studies on Molecular Mechanisms of Insulin Resistance

“…Journal of Diabetes Research [37], South Africans of mixed-ancestry [38], Chinese [39,40], Americans, Europeans, Africans [41], Asians [42], and Zanjans [43], but others have found no link in Pakistani Punjabis [44], Malaysians [45], Lebanese and Tunisians [46], Chinese [47,48], and Danish Caucasians [49]. To understand its specific molecular significance in insulin resistance, more research with bigger sample sizes is required.…”