Chromosome 4q locus associated with insulin resistance in Pima Indians. Studies in three European NIDDM populations.
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)
Humphreys
P
P
Department of Medicine, Addenbrooke's Hospital, University of Cambridge, U.K.
McCarthy
M
M
Tuomilehto
J
J
Tuomilehto-Wolf
E
E
Stratton
I
I
Morgan
R
R
Rees
A
A
Owens
D
D
Stengård
J
J
Nissinen
A
A
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*
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