Genomic structure and mutations in adipose-specific gene, adiponectin.
BACKGROUND
Adiponectin is a collagen-like plasma protein specifically synthesized in adipose tissue. Plasma adiponectin concentrations are decreased in obesity whereas it is adipose-specific.


OBJECTIVE
To clarify the significance of the genetic variations in adiponectin gene on its plasma concentrations and obesity.


METHODS
Two hundred and nineteen unrelated adult Japanese subjects (123 men and 96 women, age: 20-83 y, BMI: 16-43 kg/m2) including 77 obese subjects (BMI>26.4 kg/m2).


METHODS
Human adiponectin gene was isolated from PAC DNA pools. Mutations in the adiponectin gene were screened by direct sequencing or restriction-fragment polymorphism. The levels of plasma adiponectin were determined by the enzyme-linked immunosorbent assay (ELISA).


RESULTS
Adiponectin gene spanned 17 kb on chromosome 3q27, consisting of three exons and two introns. Within 2.1 kb of the 5'-flanking region, there were two octamer elements present in the promoter of adipsin. Two nucleotide changes were identified. One was a polymorphism (G/T) occurring in exon 2, and the other was a missense mutation (R112C) in exon 3. The mean plasma adiponectin levels of the subjects carrying G allele were low (G/G: 4.5 microg/ml; G/T: 5.9 microg/ml; and T/T: 6.3 microg/ml), but were not statistically significant. The allelic frequency between the obese and the non-obese showed no significant difference. The subject carrying R112C mutation showed markedly low concentration of plasma adiponectin.


CONCLUSIONS
Two nucleotide changes have been identified in the adiponectin gene. G/T polymorphism in exon 2 was associated with neither plasma adiponectin concentrations nor the presence of obesity. A subject carrying missense mutation (R112C) showed markedly low plasma adiponectin concentration.
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
M
M
Takahashi
Y
Y
Arita
K
K
Yamagata
Y
Y
Matsukawa
K
K
Okutomi
M
M
Horie
I
I
Shimomura
K
K
Hotta
H
H
Kuriyama
S
S
Kihara
T
T
Nakamura
S
S
Yamashita
T
T
Funahashi
Y
Y
Matsuzawa
D017667:Adipocytes / Q000737:chemistry / Q000378:metabolism; D052242:Adiponectin; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015992:Body Mass Index; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007438:Introns / Q000235:genetics; D007564:Japan; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis / Q000235:genetics*; D015183:Restriction Mapping
D052242:Adiponectin; D018076:DNA, Complementary; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins