Glucokinase regulatory protein rs780094 polymorphism is associated with type 2 diabetes mellitus, dyslipidemia, non-alcoholic fatty liver disease, and nephropathy

In this editorial,we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes(Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria).Type 2 diabetes mellitus(T2DM)is a chronic disorder characterized by dysregulated glucose homeostasis.The persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications,including cardiovascular disease,re-tinopathy,neuropathy,and nephropathy.T2DM arises from a complex interplay between genetic,epigenetic,and environmental factors.Global genomic studies have identified numerous genetic variations associated with an increased risk of T2DM.Specifically,variations within the glucokinase regulatory protein(GCKR)gene have been linked to heightened susceptibility to T2DM and its associated complications.The clinical trial by Liu et al further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy development.Their findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC genotype.These findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans.

Pediatric fatty liver disease:Role of ethnicity and genetics

Non-alcoholic fatty liver disease (NAFLD) comprehends a wide range of conditions, encompassing from fatty liver or steatohepatitis with or without fibrosis, to cirrhosis and its complications. NAFLD has become the most common form of liver disease in childhood as its prevalence has more than doubled over the past 20 years, paralleling the increased prevalence of childhood obesity. It currently affects between 3% and 11% of the pediatric population reaching the rate of 46% among overweight and obese children and adolescents. The prevalence of hepatic steatosis varies among different ethnic groups. The ethnic group with the highest prevalence is the Hispanic one followed by the Caucasian and the African-American. This evidence suggests that there is a strong genetic background in the predisposition to fatty liver. In fact, since 2008 several common gene variants have been implicated in the pathogenesis of fatty liver disease. The most important is probably the patatin like phospholipase containing domain 3 gene (PNPLA3) discovered by the Hobbs’ group in 2008. This article reviews the current knowledge regarding the role of ethnicity and genetics in pathogenesis of pediatric fatty liver.

Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria

BACKGROUND Diabetic kidney disease is one of the common complications of type 2 diabetes(T2D).There are no typical symptoms in the early stage,and the disease will progress to moderate and late stage when albuminuria reaches a high level.Treatment is difficult and the prognosis is poor.At present,the pathogenesis of diabetic kidney disease is still unclear,and it is believed that it is associated with genetic and environmental factors.AIM To explore the relationship between the glucokinase regulatory protein(GCKR)gene rs780094 polymorphism and T2D with albuminuria.METHODS We selected 252 patients(126 males and 126 females)with T2D admitted to our hospital from January 2020 to October 2020,and 66 healthy people(44 females and 22 males).According to the urinary albumin/creatinine ratio,the subjects were divided into group I(control),group II(T2D with normoalbuminuria),group III(T2D with microalbuminuria),and group IV(T2D with macroalbuminuria).Additionly,the subjects were divided into group M(normal group)or group N(albuminuria group)according to whether they developed albuminuria.We detected the GCKR gene rs780094 polymorphism(C/T)of all subjects,and measured the correlation between GCKR gene rs780094 polymorphism(C/T)and T2D with albuminuria.RESULTS Gene distribution and genotype distribution among groups I-IV accorded with the Hardy-Weinberg equilibrium.Genotype frequency was significantly different among the four groups (P = 0.048, χ^(2)= 7.906). T allele frequency in groups II, III, and IV was significantly higherthan that in group I. Logistic regression analysis of the risk factors for T2D with albuminuria showed that the CT +TT genotype (odds ratio = 1.710, 95% confidence interval: 1.172-2.493) was a risk factor.CONCLUSION CT + TT genotype is a risk factor for T2D with albuminuria. In the future, we can assess the risk of individualscarrying susceptible genes to delay the onset of T2D.

Association of GCKR Gene Polymorphisms with the Risk of Nonalcoholic Fatty Liver Disease and Coronary Artery Disease in a Chinese Northern Han Population

Background and Aims: Accumulated studies have eval-uated the effects of glucokinase regulatory protein(GCKR)gene polymorphisms on the risk of nonalcoholic fatty liver disease(NAFLD)and coronary artery disease(CAD),but the association of GCKR polymorphisms with the risk of NAFLD and CAD in the Chinese Han population have remained un-clear.The aim of this study was to investigate the association between GCKR gene polymorphisms(rs780094 and rs1260326)and the risk of NAFLD and CAD in NAFLD patients in a Chinese Northern Han population.Methods: GCKR rs780094 and rs1260326 gene polymorphisms were geno-typed by polymerase chain reaction sequencing for B-type ultrasonography-proven NAFLD patients with(n = 82)or without(n = 142)CAD,and in healthy controls(n = 152).Serum lipid profiles'levels were determined using biochemi-cal methods.Statistical analyses were conducted using SPSS 22.0 statistical software.Results: As the results showed,sig-nificant differences in the serum lipid profiles existed between each group.No significant differences were observed in the distributions of genotypes and alleles of GCKR rs780094 and rs1260326 in each group.The GCKR rs780094 T and rs1260326 T allele carriers possessed decreased body mass index value,and serum fasting plasma glucose and TG levels in the overall subjects,respectively.In addition,the GCKR rs780094 T allele carriers possessed decreased serum fasting plasma glucose level in the controls and NAFLD+CAD patients.Conclusions: GCKR rs780094 and rs1260326 poly-morphisms were found to be not associated with the risk of NAFLD nor of CAD in NAFLD patients in this Chinese Northern Han population.GCKR rs780094 T and rs1260326 T alleles could affect the body mass index value and serum fasting plasma glucose and triglyceride levels.