title: Chromosome 4q locus associated with insulin resistance in Pima Indians. Studies in three European NIDDM populations.
abstract: Markers on chromosome 4q have recently been shown to be associated with insulin resistance in Pima Indians, a population in which insulin resistance precedes and predicts the development of non-insulin-dependent diabetes mellitus (NIDDM). To examine whether genes in this region could play a major role in susceptibility to NIDDM in other populations, we have examined the allele frequencies of a trinucleotide repeat near the fatty acid-binding protein 2 (FABP2) gene on 4q28-31 in three European populations: Finnish, U.K. Caucasian, and Welsh. The U.K. NIDDM population was selected for insulin resistance by studying patients whose obesity-corrected fasting plasma insulin before treatment was above the 98th percentile. Seven alleles were detected. On cross-tabulation analysis, there were no significant associations between allele frequencies and glucose intolerance in any of the populations. Log-linear analysis of the results from all three populations suggested a moderately significant interaction of glucose tolerance status (normal versus diabetic) and the FABP2 allele (partial chi 2 = 24, df 6, P = 0.027). The parameter describing the interaction of allele A3 and glucose tolerance status was the only such parameter differing significantly from zero (z-score +2.003, P = 0.046). In both the Finnish and U.K. population, the A3 allele was found approximately twice as frequently in NIDDM than in control subjects (Finnish control subjects, impaired glucose tolerance, and NIDDM: 12.2, 22.4, and 26.6%, respectively; U.K. control subjects and NIDDM: 7.8 and 14.6%, respectively). In the Finnish populations, no associations were found between FABP2 alleles and plasma insulin levels or with homeostatic model assessment (HOMA) estimates of beta-cell function and insulin sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Addenbrooke's Hospital, University of Cambridge, U.K.
authors.forename: P
authors.initials: P
authors.lastname: Humphreys
authors.forename: M
authors.initials: M
authors.lastname: McCarthy
authors.forename: J
authors.initials: J
authors.lastname: Tuomilehto
authors.forename: E
authors.initials: E
authors.lastname: Tuomilehto-Wolf
authors.forename: I
authors.initials: I
authors.lastname: Stratton
authors.forename: R
authors.initials: R
authors.lastname: Morgan
authors.forename: A
authors.initials: A
authors.lastname: Rees
authors.forename: D
authors.initials: D
authors.lastname: Owens
authors.forename: J
authors.initials: J
authors.lastname: Stengård
authors.forename: A
authors.initials: A
authors.lastname: Nissinen
mesh_terms: D000368:Aged; D000483:Alleles; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism; D005387:Finland; D020022:Genetic Predisposition to Disease; D018149:Glucose Intolerance / Q000235:genetics; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D011110:Polymorphism, Genetic; D012016:Reference Values; D025521:Tumor Suppressor Proteins; D006113:United Kingdom; D014852:Wales; D044465:White People / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D017931:DNA Primers; C493404:FABP2 protein, human; C107608:FABP7 protein, human; C493405:Fabp2 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins