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Plasma Resistin, Associated With Single Nucleotide Polymorphism –420, Is Correlated With Insulin Resistance, Lower HDL Cholesterol, and High-Sensitivity C-Reactive Protein in the Japanese General Population

¹ Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Ehime, Japan
² Department of Basic Medical Research and Education, Ehime University Graduate School of Medicine, Ehime, Japan
³ Department of Internal Medicine, Seiyo-city Nomura Hospital, Ehime, Japan
⁴ Department of Human Genetics, School of International Health, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
⁵ Department of Biochemistry, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
⁶ CREST, Japan Science and Technology Agency, Fukui, Japan
⁷ Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Ehime, Japan

Address correspondence and reprint requests to H. Osawa, MD, PhD, Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan. E-mail: harosawa{at}m.ehime-u.ac.jp. Or H. Makino, MD, PhD, Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan. E-mail: hidemak{at}m.ehime-u.ac.jp

OBJECTIVE—Resistin, secreted from adipocytes, causes insulin resistance in rodents. We previously reported that the G/G genotype of a resistin gene promoter single nucleotide polymorphism (SNP) at –420 increases type 2 diabetes susceptibility by enhancing promoter activity. We report here on the relation between plasma resistin and either SNP –420 genotype or factors related to insulin resistance.

RESEARCH DESIGN AND METHODS—We cross-sectionally analyzed 2,078 community-dwelling Japanese subjects attending a yearly medical checkup. The SNP –420 genotype was determined by TaqMan analysis. Fasting plasma resistin was measured using an enzyme-linked immunosorbent assay kit.

RESULTS—Plasma resistin was associated with the SNP –420 genotype (P < 0.0001), which was highest in G/G followed by C/G and C/C. Plasma resistin was higher in elderly individuals, female subjects, nondrinkers, and subjects with high blood pressure (P < 0.001, 0.003, <0.001, and 0.001, respectively). Simple regression analysis revealed that age, female sex, homeostasis model assessment of insulin resistance (HOMA-IR) index, systolic blood pressure, low HDL cholesterol, and high-sensitivity C-reactive protein (hs-CRP) were positively correlated with plasma resistin (P < 0.001, 0.003, <0.001, 0.004, <0.001, and 0.003, respectively). Multiple regression analysis adjusted for age, sex, and BMI revealed that plasma resistin was an independent factor for HOMA-IR, low HDL cholesterol, and hs-CRP (P = 0.001, <0.001, and 0.006, respectively).

CONCLUSIONS—Plasma resistin was associated with SNP –420 and was correlated with insulin resistance, low serum HDL cholesterol, and high hs-CRP in the Japanese general population.

Abbreviations: CRP, C-reactive protein • CVD, cardiovascular disease • FPG, fasting plasma glucose • HOMA-IR, homeostasis model assessment of insulin resistance • hs-CRP, high-sensitivity CRP • IRI, immunoreactive insulin • SNP, single nucleotide polymorphism • SBP, systolic blood pressure

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