Regulatory SNP in theRBP4Gene Modified the Expression in Adipocytes and Associated With BMI
| Autor: | Yoshinori Hosoya, Khadbaatar Zolzaya, Yasuo Kagawa, Shun Ishibashi, Tserenkhuu Lkhagvasuren, Maki Kumada, Toshinori Omi, Takaya Gotoh, Kazuhiro Nakayama, Masanobu Hyodo, Sadahiko Iwamoto, Hiroyuki Fujiwara, Yoshiko Yanagisawa, Nanami Utsumi, Hisanaga Horie, Lkhagvasuren Munkhtulga, Shuichi Nagashima, Masayuki Kojima |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Genotype Endocrinology Diabetes and Metabolism Medicine (miscellaneous) Electrophoretic Mobility Shift Assay Biology Polymorphism Single Nucleotide Body Mass Index Cell Line Endocrinology Asian People Gene Frequency Adipocytes Humans SNP Genetic Predisposition to Disease Electrophoretic mobility shift assay Allele Promoter Regions Genetic Gene Transcription factor Alleles Cells Cultured Genetic Association Studies Genetics Messenger RNA Chi-Square Distribution Nutrition and Dietetics Pioglitazone Patient Selection Molecular biology Minor allele frequency Haplotypes Adipogenesis Female Thiazolidinediones Insulin Resistance Retinol-Binding Proteins Plasma |
| Zdroj: | Obesity. 18:1006-1014 |
| ISSN: | 1930-7381 |
| DOI: | 10.1038/oby.2009.358 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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