Kitamoto Aya, Kitamoto Takuya, So Rina, Matsuo Tomoaki, Nakata Yoshio, Hyogo Hideyuki, Ochi Hidenori, Nakamura Takahiro, Kamohara Seika, Miyatake Nobuyuki, Kotani Kazuaki, Mineo Ikuo, Wada Jun, Ogawa Yuji, Yoneda Masato, Nakajima Atsushi, Funahashi Tohru, Miyazaki Shigeru, Tokunaga Katsuto, Masuzaki Hiroaki, Ueno Takato, Chayama Kazuaki, Hamaguchi Kazuyuki, Yamada Kentaro, Hanafusa Toshiaki, Oikawa Shinichi, Sakata Toshiie, Tanaka Kiyoji, Matsuzawa Yuji, Hotta Kikuko
Pharmacogenomics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
Endocr J. 2015;62(6):513-21. doi: 10.1507/endocrj.EJ14-0574. Epub 2015 Mar 31.
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.
内脏脂肪堆积会导致胰岛素抵抗的发展，进而引发代谢综合征。脂联素在内脏脂肪堆积和胰岛素抵抗之间起到了联系作用。除环境因素外，遗传因素在内脏脂肪堆积和循环脂联素水平中也发挥着重要作用。全基因组关联研究（GWAS）已经确定了脂联素、C1Q和胶原结构域包含蛋白（ADIPOQ）基因中的遗传变异与脂联素水平相关。在本研究中，我们调查了ADIPOQ单核苷酸多态性（SNP）是否与内脏脂肪堆积和胰岛素抵抗相关。我们通过计算机断层扫描（CT）测量了内脏脂肪面积（VFA），并在一组日本个体（731名男性和864名女性）中检测了胰岛素抵抗相关表型（空腹血糖、空腹胰岛素和稳态模型评估胰岛素抵抗[HOMA-IR]）的存在情况，这些个体针对最近GWAS报道的7个ADIPOQ SNP进行了基因分型（即rs6810075、rs10937273、rs1648707、rs8642655、rs182052、rs17366568和rs6773957）。然后，使用另一组研究参与者（383名男性和510名女性）通过关联分析评估与该表型相关的SNP（P < 0.05）。在男性或女性中，没有一个SNP与体重指数（BMI）或VFA相关。然而，rs10937273和rs1648707的降低脂联素的等位基因在女性中与HOMA-IR显著相关（分别为P = 0.0030和P = 0.00074），独立于BMI。这些SNP与女性脂联素水平降低显著相关。我们的结果表明，rs10937273和rs1648707可能通过调节女性脂肪组织中脂联素的产生来影响胰岛素敏感性。
