ABSTRACT
The increased prevalence of diabetes mellitus has caused a rise in the occurrence of its chronic complications, such as diabetic nephropathy (DN), which is associated with elevated morbidity and mortality. Familial aggregation studies have demonstrated that besides the known environmental risk factors, DN has a major genetic component. Therefore, it is necessary to identify genes associated with risk for or protection against DN. Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is expressed in several tissues, including the kidneys. Increased levels of ENPP1 expression inhibit tyrosine-kinase activity of the insulin receptor in several cell types, leading to insulin resistance. K121Q polymorphism of the ENPP1 gene seems to be associated with insulin resistance and DN development. The elucidation of genetic factors and their associations will provide better understanding of the pathogenesis of DN and, may consequently, lead to a more effective approach to prevention and treatment.
A crescente prevalência do diabetes melito tem causado aumento na ocorrência das suas complicações crônicas, como a nefropatia diabética (ND), a qual está associada com elevada morbidade e mortalidade. Estudos de agregação familiar demonstram que a ND tem um importante componente genético, além dos conhecidos fatores de risco ambientais. Portanto, existe a necessidade de se identificarem genes associados ao risco ou proteção à ND. A ectonucleotide pyrophosphatase/phosphodiesterase 1(ENPP1) é expressa em vários tecidos, incluindo nos rins. Foi encontrado que níveis aumentados de expressão da ENPP1 inibem a atividade tirosino-quinase do receptor da insulina em vários tipos celulares, causando resistência à insulina. O polimorfismo K121Q do gene ENNP1parece estar associado com resistência à insulina e com o desenvolvimento da ND. A elucidação dos fatores genéticos e de suas associações permitirá um melhor entendimento da patogênese da ND e, consequentemente, poderemos ter uma abordagem mais efetiva em sua prevenção e tratamento.
Subject(s)
Humans , /enzymology , Diabetic Nephropathies/enzymology , Insulin Resistance/genetics , Phosphoric Diester Hydrolases/genetics , Polymorphism, Genetic/genetics , Pyrophosphatases/genetics , /genetics , Diabetic Nephropathies/genetics , Genetic Markers , Genetic Predisposition to DiseaseABSTRACT
BACKGROUND: Metabolic syndrome is a cluster of several metabolic disorders (central obesity, dyslipidemia, hyperglycemia, and hypertension). It is closely related to the cardiovascular risk factors. ENPP1 is an inhibitor of insulin-induced activation of the insulin receptor. The aim of this study was to investigate the association between ENPP1 K121Q polymorphism and metabolic syndrome in Korean. METHODS: We measured BMI, waist circumference, blood pressure, lipid profile, fasting glucose in the participants who visited Health Promotion Center, Jeju National University Hospital from February to July 2008. ENPP1 K121Q polymorphism was determined by restriction fragment-length polymorphism polymerase chain reaction in 84 patients with metabolic syndrome and 114 control group. RESULTS: The frequencies of ENPP1 K121Q polymorphism were 27.4% in metabolic syndrome and 9.6% in control group. BMI, waist circumference, blood pressure were increased in male K121Q group and triglyceride was increased in female K121Q group. CONCLUSION: K121Q polymorphism was more frequent in the patients with metabolic syndrome among Koreans. There were differences of the metabolic components according to the genotype. It supports the K121Q polymorphism was associated with the genetic susceptibility for metabolic syndrome.
Subject(s)
Female , Humans , Male , Blood Pressure , Dyslipidemias , Fasting , Genetic Predisposition to Disease , Genotype , Glucose , Health Promotion , Hyperglycemia , Obesity , Polymerase Chain Reaction , Receptor, Insulin , Risk Factors , Waist CircumferenceABSTRACT
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 percent, KQ = 48.2 percent, and QQ = 25.9 percent) and BD (KK = 22.0 percent, KQ = 53.8 percent, and QQ = 24.2 percent) compared to European descendant type 2 DM patients (KK = 62.7 percent, KQ = 33.3 percent, and QQ = 4.1 percent) and BD (KK = 61.0 percent, KQ = 35.6 percent, and QQ = 3.4 percent). 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.