title: ADIPOQ polymorphisms are associated with insulin resistance in Japanese women.
abstract: Visceral fat accumulation contributes to the development of insulin resistance, leading to metabolic syndrome. Adiponectin provides a link between visceral fat accumulation and insulin resistance. In addition to environmental factors, genetic factors play important roles in visceral fat accumulation and circulating adiponectin levels. Genome-wide association studies (GWASs) have identified genetic variations in the adiponectin, C1Q and collagen domain containing (ADIPOQ) gene that are associated with adiponectin levels. In this study, we investigated whether ADIPOQ single nucleotide polymorphisms (SNPs) were associated with visceral fat accumulation and insulin resistance. We measured the visceral fat area (VFA) by computed tomography (CT) and examined the presence of the insulin resistance-related phenotype (fasting plasma glucose, fasting insulin, and homeostasis model assessment-insulin resistance [HOMA-IR]) in a set of Japanese individuals (731 men and 864 women) who were genotyped for seven ADIPOQ SNPs reported by recent GWASs (namely, rs6810075, rs10937273, rs1648707, rs864265, rs182052, rs17366568, and rs6773957). SNPs associated with the phenotype (P < 0.05) were then evaluated by association analysis using a second set of the study participants (383 men and 510 women). None of the SNPs was associated with body mass index (BMI) or VFA in men or women. However, the adiponectin-decreasing alleles of rs10937273 and rs1648707 were significantly associated with HOMA-IR (P = 0.0030 and P = 0.00074, respectively) in women, independently of BMI. These SNPs were significantly associated with decreased adiponectin levels in women. Our results suggested that rs10937273 and rs1648707 may affect insulin sensitivity by regulating adiponectin production by adipose tissue in women.
authors.affiliation: Pharmacogenomics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kitamoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Kitamoto
authors.forename: Rina
authors.initials: R
authors.lastname: So
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Matsuo
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Nakata
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hyogo
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ochi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Seika
authors.initials: S
authors.lastname: Kamohara
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyatake
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kotani
authors.forename: Ikuo
authors.initials: I
authors.lastname: Mineo
authors.forename: Jun
authors.initials: J
authors.lastname: Wada
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Masato
authors.initials: M
authors.lastname: Yoneda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyazaki
authors.forename: Katsuto
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Masuzaki
authors.forename: Takato
authors.initials: T
authors.lastname: Ueno
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hamaguchi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamada
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oikawa
authors.forename: Toshiie
authors.initials: T
authors.lastname: Sakata
authors.forename: Kiyoji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: Kikuko
authors.initials: K
authors.lastname: Hotta
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D050154:Adiposity; D000328:Adult; D000368:Aged; D000483:Alleles; D015992:Body Mass Index; D015536:Down-Regulation; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012727:Sex Characteristics; D014057:Tomography, X-Ray Computed
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin