Associations between single-nucleotide polymorphisms of ADIPOQ, serum adiponectin and increased type 2 diabetes mellitus risk in Bahraini individuals.

This study aimed to estimate the frequency of the SNPs (+45T>G and +276G>T) genotypes and investigate the association between the two SNPs and adiponectin concentration, metabolic parameters and risk of T2DM in the Bahraini population. We genotyped the two ADIPOQ SNPs in 140 unrelated T2DM patients and 66 nondiabetic controls using the polymerase chain reaction-restriction fragment length polymorphism assay. Lipid profile was measured by enzymatic methods. Total serum adiponectin levels were measured by immunoassay. T2DM patients had reduced adiponectin levels compared with controls. +45T>G was more prevalent in patients than controls. The rare G allele of +45T>G occurred more frequently than the common T allele in T2DM patients compared with controls, and was associated with lower serum adiponectin levels. There was no significant difference in allele and genotype frequencies of +276G>T between type T2DM patients and controls. There was no association between both SNPs and metabolic parameters.

Associations between single-nucleotide polymorphisms of ADIPOQ, serum adiponectin and increased type 2 diabetes mellitus risk in Bahraini individuals

This study aimed to estimate the frequency of the SNPs [+45T>G and +276G>T] genotypes and investigate the association between the two SNPs and adiponectin concentration, metabolic parameters and risk of T2DM in the Bahraini population. We genotyped the two ADIPOQ SNPs in 140 unrelated T2DM patients and 66 nondiabetic controls using the polymerase chain reaction-restriction fragment length polymorphism assay. Lipid profile was measured by enzymatic methods. Total serum adiponectin levels were measured by immunoassay. T2DM patients had reduced adiponectin levels compared with controls. +45T>G was more prevalent in patients than controls. The rare G allele of +45T>G occurred more frequently than the common T allele in T2DM patients compared with controls, and was associated with lower serum adiponectin levels. There was no significant difference in allele and genotype frequencies of +276G>T between type T2DM patients and controls. There was no association between both SNPs and metabolic parameters

La présente étude avait pour objectif de mesurer la fréquence des polymorphismes mononucléotidiques [+45T>G et +276G>T] des génotypes et d'évaluer l'association entre ces deux polymorphismes et la concentration d'adiponectine, les paramètres métaboliques et le risque de diabète non insulino-dépendant [DNID] dans la population bahreinienne. Nous avons génotypé les deux polymorphismes mononucléotidiques du gène ADIPOQ chez 140 patients atteints de DNID sans lien de parenté et 66 témoins non diabétiques en recourant à l'analyse du polymorphisme de longueur des fragments de restriction par réaction en chaîne de polymérase. Le profil lipidique a été mesuré au moyen de méthodes enzymatiques. Les concentrations d'adiponectine totale sérique ont été mesurées par immunodosage. Les patients atteints de DNDI affichaient des concentrations d'adiponectine réduites par rapport aux témoins. Le polymorphisme +45T>G avait une prévalence plus élevée chez les patients que chez les témoins. L'allèle rare G du polymorphisme +45T>G apparaissait plus fréquemment que l'allèle commun T chez les patients atteints de DNID que chez les témoins, et était associé à des concentrations d'adiponectine sérique plus faibles. Il n'existait pas de différence significative entre les fréquences des allèles et des génotypes du polymorphisme +276G>T entre les patients atteints de DNID et les témoins. Aucune association entre les deux polymorphismes et les paramètres métaboliques n'a été notée

Role of dystrophin isoforms and associated proteins in muscular dystrophy (review).

The membrane cytoskeletal component dystrophin and its associated glycoproteins play a central role in the molecular pathogenesis of several muscular dystrophies, i.e. Duchenne/Becker muscular dystrophy, congenital muscular dystrophy and various forms of limb-girdle muscular dystrophy. Although the most frequent of these disorders, Duchenne muscular dystrophy, is mainly recognized as a disease of skeletal muscle fibers, pathophysiological changes also involve the heart and diaphragm, as well as the peripheral and central nervous system. Thus current research efforts into the elucidation of the molecular mechanisms underlying these genetic diseases are not only directed towards studying skeletal muscle necrosis but also investigate abnormalities of heart and brain dystrophin-glycoprotein complexes in cardiomyopathy and brain deficiencies associated with muscular dystrophy. Furthermore, many isoforms of dystrophin and dystrophin-associated components have been identified in various non-muscle tissues and their function(s) are mostly unknown. With respect to skeletal muscle fibers, the characterization of new dystrophin-associated proteins, such as dystrobrevin, sarcospan and the syntrophins, led to a modified model of the spatial configuration of the dystrophin-glycoprotein complex. However, it is generally accepted now that beta-dystroglycan forms the plasmalemma-spanning linkage between dystrophin and the laminin-binding protein alpha-dystroglycan and that this complex is associated with the sarcoglycan subcomplex of sarcolemmal glycoproteins.

Decreased expression of brain beta-dystroglycan in Duchenne muscular dystrophy but not in the mdx animal model.

Abnormalities in the muscle dystrophin-glycoprotein complex are implicated in the molecular pathogenesis of various neuromuscular disorders. Weakening of the trans-sarcolemmal linkage between the actin membrane-cytoskeleton and the extracellular matrix appears to trigger destabilization of the muscle cell periphery. In addition to muscular weakness, one-third of patients suffering from Duchenne muscular dystrophy exhibit mental retardation. Since little is known about the pathophysiology of brain abnormalities in these patients, we investigated the fate of the most abundant dystrophin-associated protein, beta-dystroglycan, in the central nervous system. It was found to be present throughout all normal brain regions studied. In contrast, this glycoprotein was greatly reduced in brain microsomes derived from Duchenne specimens, while it is of normal abundance in the brain from the dystrophic animal model mdx. Deficiency in brain beta-dystroglycan might render nervous tissue more susceptible to cellular disturbances and this may result in cognitive impairment in some Duchenne patients.