CLINICAL RESEARCH: ATHEROSCLEROSIS
Adiponectin I164T mutation is associated with the metabolic syndrome and coronary artery disease
Koji Ohashi, MD*,
Noriyuki Ouchi, MD, PhD*,
Shinji Kihara, MD, PhD*,*,
Tohru Funahashi, MD, PhD*,
Tadashi Nakamura, MD, PhD*,
Satoru Sumitsuji, MD ,
Toshiharu Kawamoto, MD, PhD ,
Satoru Matsumoto, MD||,
Hiroyuki Nagaretani, MD*,
Masahiro Kumada, MD*,
Yoshihisa Okamoto, MD*,
Hitoshi Nishizawa, MD, PhD*,
Ken Kishida, MD, PhD*,
Norikazu Maeda, MD*,
Hisatoyo Hiraoka, MD, PhD*,
Yoshio Iwashima, MD ,
Kazuhiko Ishikawa, MD, PhD,
Mitsuru Ohishi, MD, PhD,
Tomohiro Katsuya, MD, PhD,
Hiromi Rakugi, MD, PhD,
Toshio Ogihara, MD, PhD and
Yuji Matsuzawa, MD, PhD*
* Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Japan
Department of Geriatric Medicine, Graduate School of Medicine, Osaka University, Izumisano, Japan
Department of Cardiology, Rinku General Medical Center, Rinku, Japan
Department of Cardiology, National Hospital Kure Medical Center, Kure, Japan
|| Department of Cardiology, Toyonaka Municipal Hospital, Toyonaka, Japan
Manuscript received April 21, 2003;
revised manuscript received September 12, 2003,
accepted October 20, 2003.
* Reprints requests and correspondence: Dr. Shinji Kihara, Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
kihara{at}imed2.med.osaka-u.ac.jp
OBJECTIVES: 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.
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Abbreviations and Acronyms
| | BMI | = body mass index | | CAD | = coronary artery disease | | HbA1C | = hemoglobin A1C | | HDL-chol | = high-density lipoprotein cholesterol | | HOMA | = homeostasis model assessment | | PCR | = polymerase chain reaction | | SNP | = single nucleotide polymorphism | | T-chol | = total cholesterol | | TG | = triglyceride | | TNF | = tumor necrosis factor |
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