Posted by James
All type-1 diabetes cases were African-American, randomly selected from a Washington, DC population-based type-1 diabetes registry. The patients included in this registry were collected between from 1990 to 1999 as part of the World Health Organization’s multinational Project for Childhood Diabetes (Diamond project). The age range of disease onset was 0.5-17 years and the male/female ratio was 0.733. The World Health Organization (WHO) definition of type-1 diabetes was employed for this study. The criteria include history of ketoacidosis and daily insulin injection before the 17th birthday. All patients were residents of the Washington, DC metropolitan area at the time of the first insulin administration.
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Posted by James
INTRODUCTION
Polymorphisms in the tyrosine hydroxylase-insulin-insulin like growth factor 2 gene-regions (TH-INS-IGF2) on chromosome 11 were shown to have an association with type-1 diabetes. It is not yet clear whether TH gene carries susceptibility for type-1 diabetes. In the human, hTH molecules are encoded by at least three distinct messenger RNAs. The expression of these mRNAs varies in different parts of the nervous system. The calculated relative molecular mass of the deduced protein sequence is 55,473. Tyrosine hydroxylase is the first enzyme in the pathway of catecholamine synthesis. It catalyzes the formation of 3,4-dihydrox-yphenylalanine (DOPA) from tyrosine. hTH plays a central role in the neuronal transmission and hormonal action of catecholamines. Expression of the hTH gene is regulated in a tissue-specific fashionand is modulated by a variety of factors, such as cyclic AMP, glucorticoids, and trans-synaptic stimuli. The pathogenesis of some disorders of cate-cholaminergic neurons, such as schizophrenia, may be related to changes in hTH. The role of hTH in the pathogenesis of type-1 diabetes is not known, but many investigators are examining target organs, such as islet cell nerve and retina, for possible functional roles of hTH polymorphism. The hTH gene is located on chromosome llpl5.5 is composed of 14 exons interrupted by 13 introns, and spans ~8.5 kb.
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