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Regulatory SNP in the RBP4 Gene Modified the Expression in Adipocytes and Associated With BMI
Author(s) -
Munkhtulga Lkhagvasuren,
Nagashima Shuichi,
Nakayama Kazuhiro,
Utsumi Nanami,
Yanagisawa Yoshiko,
Gotoh Takaya,
Omi Toshinori,
Kumada Maki,
Zolzaya Khadbaatar,
Lkhagvasuren Tserenkhuu,
Kagawa Yasuo,
Fujiwara Hiroyuki,
Hosoya Yoshinori,
Hyodo Masanobu,
Horie Hisanaga,
Kojima Masayuki,
Ishibashi Shun,
Iwamoto Sadahiko
Publication year - 2010
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2009.358
Subject(s) - single nucleotide polymorphism , retinol binding protein 4 , minor allele frequency , biology , snp , adipocyte , allele , adipogenesis , transcription factor , gene , endocrinology , genetics , medicine , adipokine , insulin resistance , adipose tissue , genotype , insulin
Retinol‐binding protein 4 (RBP4) is a recently identified adipokine that was involved in insulin resistance. RBP4 is predominantly expressed from the liver in normal metabolic state to transport retinoids throughout the body, but the exact physiological function and the regulatory mechanisms of adipocyte‐derived RBP4 have not been revealed. We conducted the genetic analysis about metabolic parameters in Japanese and Mongolian; the minor allele carriers of regulatory single‐nucleotide polymorphism (SNP −803G>A) showed significantly higher BMI in Japanese men ( P = 0.009) and women ( P = 0.017), and in Mongolian women ( P = 0.009). Relative quantification of RBP4 transcripts in −803GA heterozygotes showed that the minor allele–linked haplotype‐derived mRNA was significantly more abundant than the transcript from major allele. RBP4 promoter assay in 3T3L1 adipocytes revealed that the minor allele increased the promoter activity double to triple and the administration of 9‐ cis ‐retinoic acid (RA) and 8‐bromo‐cyclic adenosine monophosphate (8‐Br‐cAMP) enhanced the activity. Multiple alignment analysis of human, mouse, rat, and cattle RBP4 promoter suggested conserved seven transcription factor binding motifs. Electrophoretic mobility shift assay showed the −803G>A SNP modulate the affinity against unidentified DNA‐binding factor, which was assumed to be a suppressive factor. These results collectively suggested that the minor allele of RBP4 regulatory SNP enhanced the expression in adipocytes, which may be associated with the adipogenesis.