Disease relevance of IGHD1-14

• Dichloromethane dehalogenase of Hyphomicrobium sp. strain DM2 [1].
• 140th ENMC International Workshop: Myotonic Dystrophy DM2/PROMM and other myotonic dystrophies with guidelines on management [2].
• Careful clinical evaluation of patients with DM2/PROMM shows that the similarities among the multisystemic myotonic disorders outweigh the differences [3].
• Dichloromethane dehalogenases from Hyphomicrobium sp. DM2 and Methylobacterium sp. DM4 displayed significantly different affinities for glutathione, but not for the dichloromethane substrate [4].
• RESULTS: Women with low adiponectin concentrations were characterized by thick IMT, higher prevalence of DM2, history of previous myocardial infarction, angina pectoris, anti-hypertensive treatment and high body mass index (BMI), waist circumference, plasma insulin, serum triglycerides, fasting glucose, HbA1c, and low serum HDL cholesterol levels [5].

High impact information on IGHD1-14

• In conclusion, in insulin-resistant relatives of DM2 patients, whole-body glucose-mediated glucose disposal is increased by GE enhancement of the muscle nonoxidative glucose pathway and by GE enhancement of the suppression of HGP [6].
• Two of the resulting ExsD charged-cluster mutants (DM2 and DM3) demonstrated a hyperrepressive phenotype for expression of the T3SS [7].
• The JH region was identical to the germline JH4 sequence except for deletion of a thymidine residue at the site of D-JH recombination, and the D region showed greatest homology to DM2 [8].
• Dichloromethane dehalogenase, a highly inducible glutathione-dependent enzyme catalyzing the conversion of dichloromethane into formaldehyde and inorganic chloride, was purified fivefold with 60% yield from Hyphomicrobium sp. strain DM2 [1].
• This insulin resistance was further aggravated by the nicotine infusion in DM2 but not in Ctr (4.6 +/- 0.3 vs. 10.9 +/- 0.3 mg kg(-1) LBM min(-1); P < 0.0001) [9].

Chemical compound and disease context of IGHD1-14

• METHODS: Blood plasma levels of cholesterol oxidation products were determined in the following groups: type 1 diabetes mellitus (DM1), type 2 diabetes (DM2), impaired glucose tolerance (IGT), children without diabetes (C1) and adults without diabetes (C2) [10].

Biological context of IGHD1-14

• CONCLUSIONS: At this low infusion rate, nicotine aggravated the insulin resistance in DM2 but not in Ctr [9].
• Genetic linkage analyses show that myotonic dystrophies can be divided into three types: the conventional Steinert type linked to chromosome 19q13.3 (DM1); DM2/PROMM and PDM linked to chromosome 3q21.3; and families not linked to either chromosomal site [3].
• Proof of genetic heterogeneity in the proximal myotonic myopathy syndrome (PROMM) and its relationship to myotonic dystrophy type 2 (DM2) [11].
• OBJECTIVE: The VNTR polymorphism in the promoter region of the insulin gene (INS-VNTR) affects transcription rate and has been associated with insulin resistance and DM2 [12].
• (iii) unifying concepts: reported actions of metformin on the mitochondrial respiratory chain, free fatty acid metabolism, AMP-activated protein kinase, and on membrane proteins directly may all explain subsets of actions that are seen, providing more integrated targets for consideration in the therapy of DM2 [13].

Anatomical context of IGHD1-14

• These results provide support for the hypothesis that ATP release from erythrocytes of humans with DM2 is impaired and this defect in erythrocyte physiology could contribute to the vascular disease associated with this clinical condition [14].
• BACKGROUND: Although diabetes confers an increased propensity toward accelerated atherogenesis, data are lacking on monocyte activity in type 2 diabetic patients with (DM2-MV) and without (DM2) macrovascular disease compared with control subjects [15].
• RESULTS: Using multi-dimensional unsupervised FOREL (FORmal ELement) algorithm we have re-analyzed three public datasets of skeletal muscle gene expression in connection with insulin resistance and type 2 diabetes (DM2) [16].
• The presence of a negative linear correlation between thyroid volume and TSH concentration was noticed in patients with DM2 (RS = -0.38, P<0.01).Conclusion: In individuals with DM1 and DM2 treated for poorly controlled disease and/or diabetic complications, thyroid volumes were significantly higher than in the normal population [17].

Associations of IGHD1-14 with chemical compounds

• The sequence of dcmA, the dichloromethane dehalogenase gene from strain DM2, was determined and featured a single base difference from the previously determined sequence of dcmA from strain DM4 [4].
• In the absence of nicotine, DM2 were more insulin resistant than Ctr (6.7 +/- 0.4 vs. 10.9 +/- 0.3 mg kg-1 LBM min(-1), respectively; P < 0.0001) [9].
• The concentrations of 7beta-hydroxycholesterol, cholesterol-alpha-epoxide and cholesterol-beta-epoxide were higher in the blood plasma of subjects in the DM2 group than in the blood plasma of subjects in the C2 and IGT groups (p < 0.05) [10].
• The only effect of glycemic optimization was a decrease in fructosamine and gLDL in LDL(+) from DM2 subjects [18].
• LDL(-) from DM2 patients presented similar differential characteristics versus LDL(+) than LDL(-) from controls; that is, decreased apoB and oxidizability, and increased triglyceride, nonesterified fatty acids (NEFA), apoE, apoC-III, platelet-activating factor (PAF) acetylhydrolase activity and aggregability [18].

Analytical, diagnostic and therapeutic context of IGHD1-14

• SUBJECTS: Six male and female type 2 diabetic patients [DM2; age 54 +/- 10 (mean +/- SD) years; body mass index (BMI) 25.6 +/- 2.9 kg m(-2)] treated with diet or one oral hypoglycaemic agent and six age- and BMI-matched control subjects (Ctr) [9].
• We investigated the serum iron indices in 41 offspring of DM2 parents (group I) with normal glucose tolerance, and in 49 offspring whose parents had no history of DM2 and were matched for sex, age, body mass index (BMI), waist to hip ratio (WHR) and blood pressure (group II) [19].

References