ABSTRACT
This study is to elucidate whether the B- and T-lymphocyte attenuator (BTLA) gene is a new susceptibility gene for the development of type 1 diabetes (T1D) and systemic lupus erythematosus (SLE). As a result, this study did not find any genetic contribution of the BTLA gene to the development of T1D and SLE in Japanese population.
Subject(s)
Diabetes Mellitus, Type 1/genetics , Genetic Predisposition to Disease , Lupus Erythematosus, Systemic/genetics , Receptors, Immunologic/genetics , Alleles , B-Lymphocytes/metabolism , Child , Gene Frequency/genetics , Genotype , Haplotypes/genetics , Humans , Polymorphism, Single Nucleotide/genetics , T-Lymphocytes/metabolismABSTRACT
OBJECTIVE: The cellular effects of growth hormone (GH) are mediated by the interaction between GH and the GH receptor (GHR). We investigated the association between polymorphisms in GHR and changes in height standard deviation scores (SDS), and lipid metabolism during GH treatment for GH-deficient children. DESIGN: A 1-year study on growth rate and lipid metabolism under GH treatment. PATIENTS: Eighty-three children (61 boys and 22 girls) with GH deficiency were treated with GH for 1 year after diagnosis. INTERVENTION: The patients were treated with recombinant human GH (0.19 mg/kg/week) for at least 1 year after diagnosis. The growth rates and biochemical parameters for lipid metabolism were measured both before and during treatment. Four single nucleotide polymorphisms (SNPs) in the GHR gene, Cys440Phe, Pro495Thr, Leu544Ile and Pro579Thr, and exon 3 deletion polymorphisms were genotyped by direct sequencing and multiplex PCR. RESULTS: We found no significant association between GHR polymorphisms and changes in height SDS during GH treatment. The total cholesterol levels of the GH-deficient boys with Ile/Ile at codon 544 showed significantly higher cholesterol levels before GH treatment and then maintained high levels during the GH treatment, compared to those with other genotypes. No other polymorphisms seemed to have any apparent effects on lipid metabolism. CONCLUSION: The Leu544Ile polymorphism of the GHR gene is associated with cholesterol levels in boys with GH deficiency.
Subject(s)
Cholesterol/blood , Human Growth Hormone/therapeutic use , Hypopituitarism/genetics , Polymorphism, Single Nucleotide , Receptors, Somatotropin/genetics , Analysis of Variance , Child , Cholesterol, HDL/blood , Exons , Female , Gene Deletion , Growth , Growth Hormone/blood , Humans , Hypopituitarism/blood , Hypopituitarism/drug therapy , Insulin-Like Growth Factor I/analysis , Linkage Disequilibrium , Lipid Metabolism , Male , Sex FactorsABSTRACT
A growing body of evidence has shown that oxidative stress may be involved in the development of vascular complications associated with diabetes. However, the molecular mechanism for increased reactive oxygen species (ROS) production in diabetes remains uncertain. Among various possible mechanisms, attention have increasingly been paid to NAD(P)H oxidase as the most important source of ROS production in vascular cells. High glucose level stimulates ROS production through protein kinase C (PKC)-dependent activation of vascular NAD(P)H oxidase. Furthermore, the expression of NAD(P)H oxidase components is increased in micro- and macrovascular tissues of diabetic animals in association with various functional disorders and histochemical abnormalities. These results suggest that vascular NAD(P)H oxidase-driven ROS production may contribute to the onset or development of diabetic micro- or macrovascular complications. In this point of view, the possible new strategy of antioxidative therapy for diabetic vascular complications is discussed in this review.