Interpretation of Genetics in Diabetes mellitus (original) (raw)

Recent advances in the molecular genetics of type 2 diabetes mellitus

World journal of diabetes, 2014

Type 2 diabetes mellitus (T2DM) is a complex disease in which both genetic and environmental factors interact in determining impaired β-cell insulin secretion and peripheral insulin resistance. Insulin resistance in muscle, liver and fat is a prominent feature of most patients with T2DM and obesity, resulting in a reduced response of these tissues to insulin. Considerable evidence has been accumulated to indicate that heredity is a major determinant of insulin resistance and T2DM. It is believed that, among individuals destined to develop T2DM, hyperinsulinemia is the mechanism by which the pancreatic β-cell initially compensates for deteriorating peripheral insulin sensitivity, thus ensuring normal glucose tolerance. Most of these people will develop T2DM when β-cells fail to compensate. Despite the progress achieved in this field in recent years, the genetic causes of insulin resistance and T2DM remain elusive. Candidate gene association, linkage and genome-wide association studie...

Genetic determinants and molecular pathways in the pathogenesis of Type 2 diabetes

Clinical Science, 2009

T2DM (Type 2 diabetes mellitus) has reached epidemic proportions worldwide, exerting major health consequences at an individual and public health level alike. Unfortunately, the molecular pathophysiology of diabetes remains incompletely understood, impairing progress towards more effective prevention and treatment strategies. Although the rapid increase in the prevalence of insulin resistance and T2DM over the past several decades highlights a major environmental contribution related to overnutrition, obesity and inactivity, susceptibility is likely to reflect individual differences in complex gene–environment interactions. In the present review, we focus on mediators of genetic and environmental risk for T2DM at a molecular level.

An insight into the genetics of type 1 Diabetes

Inmunología, 2009

RESUMEN La diabetes tipo 1 (T1D) es una enfermedad compleja causada por la destrucción autoinmune de las células beta del páncreas, fruto de la interacción entre factores genéticos y ambientales. A pesar de los enormes avances en el estudio de la T1D, los mecanismos etiológicos de la enfermedad y los factores genéticos y ambientales implicados en la misma siguen siendo en parte desconocidos. La investigación en el campo de la genética de la T1D abarca más de treinta años y se han descubierto hasta 40 regiones cromosómicas relacionadas con la susceptibilidad a T1D. Algunas de ellas, como la correspondiente al HLA o al gen de la insulina, se han establecido claramente como factores de riesgo, mientras que en otras se necesita confirmar resultados preliminares. En este texto revisaremos algunos de estos genes de susceptibilidad: los alelos del MHC de clase II, el gen de la insulina, CTLA4, PTPN22, IL2 y la subunidad de su receptor IL2RA, la helicasa IFIH1/MDA5, el bloque CAPSL-IL7R, la lectina CLEC16A, el factor de transcripción de la respuesta Th1 STAT4 y la tirosin-fosfatasa PTPN2.

Genetics of type 2 diabetes INTRODUCTION

Type 2 diabetes (T2D) is the result of interaction between environmental factors and a strong hereditary component. We review the heritability of T2D as well as the history of genetic and genomic research in this area. Very few T2D risk genes were identified using candidate gene and linkage-based studies, but the advent of genome-wide association studies has led to the identification of multiple genes, including several that were not previously known to play any role in T2D. Highly replicated genes, for example TCF7L2, KCNQ1 and KCNJ11, are discussed in greater detail. Taken together, the genetic loci discovered to date explain only a small proportion of the observed heritability. We discuss possible explanations for this "missing heritability", including the role of rare variants, gene-environment interactions and epigenetics. The clinical utility of current findings and avenues of future research are also discussed.

Genetic Aspects of Diabetes Mellitus

Acta Medica, 2001

Practically all types of diabetes mellitus (DM) result from complex interactions of genetic and environmental factors. Multifactorial and polygenic Type 1 DM is strongly influenced by genes controlling the immune system, mainly HLA-DQ and DR. In addition to this, many other predisposition loci, interacting with each other, have some influence on susceptibility to DM. Heterogeneous Type 2 DM, accounting for about 85 % of all diabetic patients, is supposed to be induced by multiple genes defects involved in insulin action and/or insulin secretion. Other genetically influenced traits like obesity and hyperlipidemia are strongly associated with the Type 2. The group called Other specific types of DM include monogenic forms MODY 1-5 and many various subtypes of the disease, where the specific gene mutations have been identified. Both genetic and intrauterine environmental influences are likely to contribute to the abnormalities defined as Gestational DM.

Genes predisposing to type 1 diabetes mellitus and pathophysiology: a narrative review

Medical Journal of Indonesia

The possibility of targeting the causal genes along with the mechanisms of pathogenically complex diseases has led to numerous studies on the genetic etiology of some diseases. In particular, studies have added more genes to the list of type 1 diabetes mellitus (T1DM) suspect genes, necessitating an update for the interest of all stakeholders. Therefore this review articulates T1DM suspect genes and their pathophysiology. Notable electronic databases, including Medline, Scopus, PubMed, and Google-Scholar were searched for relevant information. The search identified over 73 genes suspected in the pathogenesis of T1DM, with human leukocyte antigen, insulin gene, and cytotoxic T lymphocyte-associated antigen 4 accounting for most of the cases. Mutations in these genes, along with environmental factors, may produce a defective immune response in the pancreas, resulting in β-cell autoimmunity, insulin deficiency, and hyperglycemia. The mechanisms leading to these cellular reactions are g...