Identification of four amino acid substitutions in hexokinase II and studies of relationships to NIDDM, glucose effectiveness, and insulin sensitivity
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Identification of four amino acid substitutions in hexokinase II and studies of relationships to NIDDM, glucose effectiveness, and insulin sensitivity. / Echwald, Søren Morgenthaler; Bjørbaek, C; Hansen, Torben; Clausen, J O; Vestergaard, H; Zierath, J R; Printz, R L; Granner, D K; Pedersen, O.
In: Diabetes, Vol. 44, No. 3, 03.1995, p. 347-53.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Identification of four amino acid substitutions in hexokinase II and studies of relationships to NIDDM, glucose effectiveness, and insulin sensitivity
AU - Echwald, Søren Morgenthaler
AU - Bjørbaek, C
AU - Hansen, Torben
AU - Clausen, J O
AU - Vestergaard, H
AU - Zierath, J R
AU - Printz, R L
AU - Granner, D K
AU - Pedersen, O
PY - 1995/3
Y1 - 1995/3
N2 - Human hexokinase (HK) II, a glucose phosphorylating enzyme in muscle tissue, plays a central role in glucose metabolism. Since reduced insulin-stimulated glucose uptake and reduced glucose-6-phosphate content in muscle have been demonstrated in pre-non-insulin-dependent diabetes mellitus (pre-NIDDM) and NIDDM subjects, we have examined the coding region of the HKII gene in NIDDM patients to determine whether these patients show genetic polymorphisms that are associated with or contribute to the disease. Single-strand conformational polymorphism analysis and nucleotide sequencing were initially performed on the entire coding region of the HKII gene of 38 insulin-resistant NIDDM patients and 5 healthy control subjects. This analysis revealed four missense mutations at codons 142 (Gln to His), 148 (Leu to Phe), 497 (Arg to Gln), and 844 (Arg to Lys) and an additional six exon polymorphisms that did not predict any change in amino acid composition of the protein. One homozygous and nine heterozygous carriers of the codon 142 mutation were found among the NIDDM patients. The mutations at codons 148, 497, and 844 were each found in one diabetic subject and only on one allele. There were no carriers of compound heterozygous mutations. A subsequent study of 301 patients with NIDDM and 151 healthy control subjects revealed no additional mutations at codons 148, 497, or 844. The total frequency of the mutated allele at codon 142 was 18.9% among the control subjects and 17.0% among the NIDDM patients (chi 2 = 0.56, P = 0.45).(ABSTRACT TRUNCATED AT 250 WORDS)
AB - Human hexokinase (HK) II, a glucose phosphorylating enzyme in muscle tissue, plays a central role in glucose metabolism. Since reduced insulin-stimulated glucose uptake and reduced glucose-6-phosphate content in muscle have been demonstrated in pre-non-insulin-dependent diabetes mellitus (pre-NIDDM) and NIDDM subjects, we have examined the coding region of the HKII gene in NIDDM patients to determine whether these patients show genetic polymorphisms that are associated with or contribute to the disease. Single-strand conformational polymorphism analysis and nucleotide sequencing were initially performed on the entire coding region of the HKII gene of 38 insulin-resistant NIDDM patients and 5 healthy control subjects. This analysis revealed four missense mutations at codons 142 (Gln to His), 148 (Leu to Phe), 497 (Arg to Gln), and 844 (Arg to Lys) and an additional six exon polymorphisms that did not predict any change in amino acid composition of the protein. One homozygous and nine heterozygous carriers of the codon 142 mutation were found among the NIDDM patients. The mutations at codons 148, 497, and 844 were each found in one diabetic subject and only on one allele. There were no carriers of compound heterozygous mutations. A subsequent study of 301 patients with NIDDM and 151 healthy control subjects revealed no additional mutations at codons 148, 497, or 844. The total frequency of the mutated allele at codon 142 was 18.9% among the control subjects and 17.0% among the NIDDM patients (chi 2 = 0.56, P = 0.45).(ABSTRACT TRUNCATED AT 250 WORDS)
KW - Adult
KW - Alleles
KW - Amino Acid Sequence
KW - Anthropometry
KW - Base Sequence
KW - Blood Glucose
KW - Body Mass Index
KW - Codon
KW - DNA Primers
KW - Diabetes Mellitus, Type 2
KW - Exons
KW - Glucose Tolerance Test
KW - Heterozygote Detection
KW - Hexokinase
KW - Homozygote
KW - Humans
KW - Insulin
KW - Molecular Sequence Data
KW - Physical Fitness
KW - Point Mutation
KW - Polymerase Chain Reaction
KW - Polymorphism, Genetic
KW - Precancerous Conditions
KW - Reference Values
KW - Restriction Mapping
KW - Tolbutamide
M3 - Journal article
C2 - 7883123
VL - 44
SP - 347
EP - 353
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 3
ER -
ID: 92193536