Adiponectin I164T mutation is associated with the metabolic syndrome and coronary artery disease.
OBJECTIVE
This study examined the association of mutations in adiponectin gene with the prevalence of coronary artery disease (CAD).


BACKGROUND
Coronary artery disease is a major cause of mortality in the industrial countries. Adiponectin gene locus, chromosome 3q27, is the candidate site for CAD. We have reported that adiponectin has antiatherogenic and antidiabetic properties, and that the plasma levels negatively correlated with body mass index (BMI) are significantly low in patients with CAD or type 2 diabetes.


METHODS
The study subjects were 383 consecutive patients with angiographically confirmed CAD and 368 non-CAD subjects adjusted for age and BMI in the Japanese population. Single nucleotide polymorphisms (SNPs) in the adiponectin gene were determined by Taqman polymerase chain reaction (PCR) method or a PCR-based assay for the analysis of restriction fragment length polymorphism. The plasma adiponectin concentration was measured by enzyme-linked immunosorbent assay.


RESULTS
Among SNPs, the frequency of I164T mutation was significantly higher in CAD subjects (2.9%) than in the control (0.8%, p < 0.05). The plasma adiponectin levels in subjects carrying the I164T mutation were significantly lower than in those without the mutation, and were independent of BMI. In contrast, SNP94 and SNP276, which are reported to be associated with an increased risk of type 2 diabetes, were associated neither with CAD prevalence nor with plasma adiponectin level. Subjects with I164T mutation exhibited a clinical phenotype of the metabolic syndrome.


CONCLUSIONS
The I164T mutation in the adiponectin gene was a common genetic background associated with the metabolic syndrome and CAD in the Japanese population.
Ohashi
Koji
K
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Japan.
Ouchi
Noriyuki
N
Kihara
Shinji
S
Funahashi
Tohru
T
Nakamura
Tadashi
T
Sumitsuji
Satoru
S
Kawamoto
Toshiharu
T
Matsumoto
Satoru
S
Nagaretani
Hiroyuki
H
Kumada
Masahiro
M
Okamoto
Yoshihisa
Y
Nishizawa
Hitoshi
H
Kishida
Ken
K
Maeda
Norikazu
N
Hiraoka
Hisatoyo
H
Iwashima
Yoshio
Y
Ishikawa
Kazuhiko
K
Ohishi
Mitsuru
M
Katsuya
Tomohiro
T
Rakugi
Hiromi
H
Ogihara
Toshio
T
Matsuzawa
Yuji
Y
D052242:Adiponectin; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D003920:Diabetes Mellitus / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D006973:Hypertension / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D007564:Japan; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D013223:Statistics as Topic; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D001786:Blood Glucose; D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D014280:Triglycerides