Adiponectin Concentrations: A Genome-wide Association Study

Abstract

Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians. Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a two-stage design (979 subjects initially and 3,022 in a second stage). Another 2,304 subjects were used for follow-up replication studies with selected markers. In the discovery phase, the top SNP associated with mean log adiponectin was rs3865188 in CDH13 on chromosome 16 (p = 1.69 × 10(-15) in the initial sample, p = 6.58 × 10(-39) in the second genome-wide sample, and p = 2.12 × 10(-32) in the replication sample). The meta-analysis p value for rs3865188 in all 6,305 individuals was 2.82 × 10(-83). The association of rs3865188 with high-molecular-weight adiponectin (p = 7.36 × 10(-58)) was even stronger in the third sample. A reporter assay that evaluated the effects of a CDH13 promoter SNP in complete linkage disequilibrium with rs3865188 revealed that the major allele increased expression 2.2-fold. This study clearly shows that genetic variants in CDH13 influence adiponectin levels in Korean adults.

Adiponectin Level and Gene Variability Are Obesity and Metabolic Syndrome Markers in a Young Population

“…Results of these reports pointed that regional differences in body fat affected the risk of metabolic abnormalities, and also ADIPOQ gene variants were suggested as modulators of visceral fat accumulation. Identification of genes controlling adiponectin levels may aid our understanding of how genes influence MetS and possibly obesity (56). Many study results were published on associations of ADIPOQ SNPs (27,36,57) as well as haplotypes with plasma adiponectin concentrations (22,54), but the data are controversial.…”

A commentary on Association of adiponectin polymorphism with cord blood adiponectin concentrations and intrauterine growth

“…In this population the same allele, À11377G, was not found to be associated with higher adiponectin levels. 9 The finding that a SNP in the ADIPOQ gene is associated with adiponectin levels and influences body adiposity at birth reinforces the role of adiponectin in fetal development. It is tempting to continuously evaluate the cohort evaluated by Saito et al to observe whether or not these associations remain after birth.…”

<i>ADIPOQ</i> polymorphisms are associated with insulin resistance in Japanese women

“…Homeostasis causing insulin resistance and type 2 diabetes [4,5]. Recently, genome-wide association studies (GWASs) have indicated that adiponectin levels are also determined by genetic variations, in addition to visceral fat accumulation [6][7][8][9][10][11][12][13]. One of the most important genetic factors determining adiponectin level is the adiponectin, C1Q and collagen domain containing (ADIPOQ) gene itself; polymorphisms in the ADIPOQ gene have been reported to be associated with insulin resistance and type 2 diabetes, in addition to adiponectin levels [8,11,13,14].…”

“…We selected seven SNPs in the ADIPOQ gene that were recently identified by GWAS [6][7][8][9][10][11][12] and constructed Invader probes (Third Wave Technologies, Madison, WI) for these SNPs. The following seven SNPs were genotyped using Invader assays, as previously described [25], and used for analysis: rs6810075, rs10937273, rs1648707, rs864265, rs182052, rs17366568, and rs6773957.…”

“…ADIPOQ polymorphisms are associated with insulin resistance in Japanese women Aya Kitamoto 1) , Takuya Kitamoto 1) , Rina So 2) , Tomoaki Matsuo 2) , Yoshio Nakata 2) , Hideyuki Hyogo 3) , Hidenori Ochi 3) , Takahiro Nakamura 4) , Seika Kamohara 5) , Nobuyuki Miyatake 6) , Kazuaki Kotani 7) , Ikuo Mineo 8) , Jun Wada 9) , Yuji Ogawa 10) , Masato Yoneda 10) , Atsushi Nakajima 10) , Tohru Funahashi 11) , Shigeru Miyazaki 12) , Katsuto Tokunaga 13) , Hiroaki Masuzaki 14) , Takato Ueno 15) , Kazuaki Chayama 3) , Kazuyuki Hamaguchi 16) , Kentaro Yamada 17) , Toshiaki Hanafusa 18) , Shinichi Oikawa 19) , Toshiie Sakata 20) , Kiyoji Tanaka 2) , Yuji Matsuzawa 7) and Kikuko Hotta 1)…”