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PMID: 8094694 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

DNA polymorphisms in the human tyrosine hydroxylase/insulin/insulin-like growth factor II chromosomal region in relation to glucose and insulin responses.

Diabetologia ·Vol. 36 ·No. 1 ·1993-01-00 ·Pages 25-32

Sten-Linder M, Wedell A, Iselius L, Efendic S, Luft R, Luthman H

Abstract

The feasibility of disease association studies using polymorphic DNA markers in the tyrosine hydroxylase/insulin/insulin-like growth factor II chromosomal region was indicated by a high degree of linkage disequilibrium found in haplotypes. Haplotypes were resolved in the parents from Scandinavian nuclear families by studying the segregation of eight DNA polymorphisms. Comparison of observed vs expected frequencies of haplotypes, as well as pairwise measures of linkage disequilibrium, indicated a high degree of linkage disequilibrium. Five restriction fragment length polymorphisms linked to the tyrosine hydroxylase/insulin/insulin growth factor II region of chromosome 11 were investigated in relation to Type 2 (non-insulin-dependent) diabetes mellitus, and to glucose and insulin responses to glucose infusion in healthy subjects. No significant differences in genotype frequencies between Type 2 diabetic (n = 53) and healthy subjects (n = 106) were found. A significant association (p < 0.001) was initially found between genotypes defined by a PstI polymorphism located 5' of the tyrosine hydroxylase gene and the early glucose response to a standardized glucose infusion test in healthy subjects. However, a follow-up study of 112 healthy individuals failed to confirm this finding.

MeSH Terms
Alleles Base Sequence Blood Glucose/metabolism Chromosome Mapping Chromosomes, Human, Pair 11 DNA Restriction Enzymes Deoxyribonucleases, Type II Site-Specific Diabetes Mellitus, Type 2/blood,enzymology,genetics Female Genotype Haplotypes Humans Insulin/blood,genetics Insulin-Like Growth Factor II/genetics Male Middle Aged Molecular Sequence Data Oligodeoxyribonucleotides Polymorphism, Restriction Fragment Length Reference Values Restriction Mapping Tyrosine 3-Monooxygenase/genetics
Chemicals
Blood Glucose Insulin Oligodeoxyribonucleotides Insulin-Like Growth Factor II Tyrosine 3-Monooxygenase DNA Restriction Enzymes CTGCAG-specific type II deoxyribonucleases Deoxyribonucleases, Type II Site-Specific
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Sten-Linder M
Department of Clinical Genetics, Karolinska Hospital, Stockholm, Sweden.
Wedell A
Iselius L
Efendic S
Luft R
Luthman H
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Article Info
Journal
Diabetologia
Abbr.
Diabetologia
ISSN
0012-186X
DOI
10.1007/BF00399089
Published
1993-01-00
Pages
25-32
Language
English
Region
Germany
NLM ID
0006777
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00399089 View journal details
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