A genetic marker at the glucokinase gene locus for type 2 (non-insulin-dependent) diabetes mellitus in Mauritian Creoles.
The prevalence of Type 2 (non-insulin-dependent) diabetes mellitus is high in Mauritius, a multiethnic island nation in the southwestern Indian Ocean. Evaluation of candidate genes in the different ethnic groups represents a means of assessing the genetic component. As glucokinase is known to be a key regulator of glucose homeostasis in liver and pancreatic Beta-cells, the human gene was isolated and a dinucleotide repeat (CA)n marker was identified at this locus. A polymerase chain reaction assay was developed, and alleles differing in size were observed in individuals, according to the number of repeats in the amplified fragment. Eighty-five Creoles and 63 Indians of known glucose tolerance status were typed by amplification of genomic DNA for this dinucleotide (CA)n repeat marker. Four different alleles were observed including Z, the most common allele, and Z + 2, Z + 4, and Z + 10, which differed from Z by 2, 4, and 10 nucleotides respectively. In Mauritian Creoles, the frequency of the Z + 2 allele was greater in Type 2 diabetic subjects than in control subjects (23.8% vs 8.9%, p = 0.008), and the frequency of the Z allele was lower in Type 2 diabetic subjects (60% vs 75.6%, p = 0.03). Analysis with univariate logistic regression models indicated that the Z + 2 allele had the highest odds ratio, 3.08 (95% confidence interval 1.14-8.35, p = 0.0416), among the other risk factors (age, sex, body mass index, and waist/hip ratio). The multivariate odds ratio for Type 2 diabetes was 2.88 (95% confidence interval 0.98-8.50, p = 0.0551).(ABSTRACT TRUNCATED AT 250 WORDS)
Chiu
K C
KC
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
Province
M A
MA
Dowse
G K
GK
Zimmet
P Z
PZ
Wagner
G
G
Serjeantson
S
S
Permutt
M A
MA
D000349:Africa / Q000208:ethnology; D000367:Age Factors; D000483:Alleles; D000704:Analysis of Variance; D001483:Base Sequence; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D005006:Ethnicity; D005060:Europe / Q000208:ethnology; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D005941:Glucokinase / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D007194:India / Q000208:ethnology; D008270:Madagascar / Q000208:ethnology; D008297:Male; D008436:Mauritius; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D009838:Oligodeoxyribonucleotides; D012016:Reference Values; D012044:Regression Analysis; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D012727:Sex Characteristics
D005819:Genetic Markers; D006684:HLA-DR Antigens; D009838:Oligodeoxyribonucleotides; D005941:Glucokinase