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A at Single Nucleotide Polymorphism-358 Is Required for G at -420 to Confer the Highest Plasma Resistin in the General Japanese Population
Insulin resistance is a feature of type 2 diabetes. Resistin, secreted from adipocytes, causes insulin resistance in mice. We previously reported that the G/G genotype of single nucleotide polymorphism (SNP) at −420 (rs1862513) in the human resistin gene (RETN) increased susceptibility to type 2 dia...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838794/ https://www.ncbi.nlm.nih.gov/pubmed/20300528 http://dx.doi.org/10.1371/journal.pone.0009718 |
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author | Onuma, Hiroshi Tabara, Yasuharu Kawamura, Ryoichi Tanaka, Takashi Ohashi, Jun Nishida, Wataru Takata, Yasunori Ochi, Masaaki Yamada, Kazuya Kawamoto, Ryuichi Kohara, Katsuhiko Miki, Tetsuro Makino, Hideichi Osawa, Haruhiko |
author_facet | Onuma, Hiroshi Tabara, Yasuharu Kawamura, Ryoichi Tanaka, Takashi Ohashi, Jun Nishida, Wataru Takata, Yasunori Ochi, Masaaki Yamada, Kazuya Kawamoto, Ryuichi Kohara, Katsuhiko Miki, Tetsuro Makino, Hideichi Osawa, Haruhiko |
author_sort | Onuma, Hiroshi |
collection | PubMed |
description | Insulin resistance is a feature of type 2 diabetes. Resistin, secreted from adipocytes, causes insulin resistance in mice. We previously reported that the G/G genotype of single nucleotide polymorphism (SNP) at −420 (rs1862513) in the human resistin gene (RETN) increased susceptibility to type 2 diabetes by enhancing its promoter activity. Plasma resistin was highest in Japanese subjects with G/G genotype, followed by C/G, and C/C. In this study, we cross-sectionally analyzed plasma resistin and SNPs in the RETN region in 2,019 community-dwelling Japanese subjects. Plasma resistin was associated with SNP-638 (rs34861192), SNP-537 (rs34124816), SNP-420, SNP-358 (rs3219175), SNP+299 (rs3745367), and SNP+1263 (rs3745369) (P<10(−13) in all cases). SNP-638, SNP -420, SNP-358, and SNP+157 were in the same linkage disequilibrium (LD) block. SNP-358 and SNP-638 were nearly in complete LD (r(2) = 0.98), and were tightly correlated with SNP-420 (r(2) = 0.50, and 0.51, respectively). The correlation between either SNP-358 (or SNP-638) or SNP-420 and plasma resistin appeared to be strong (risk alleles for high plasma resistin; A at SNP-358, r(2) = 0.5224, P = 4.94×10(−324); G at SNP-420, r(2) = 0.2616, P = 1.71×10(−133)). In haplotypes determined by SNP-420 and SNP-358, the estimated frequencies for C-G, G-A, and G-G were 0.6700, 0.2005, and 0.1284, respectively, and C-A was rare (0.0011), suggesting that subjects with A at −358, generally had G at −420. This G-A haplotype conferred the highest plasma resistin (8.24 ng/ml difference/allele compared to C-G, P<0.0001). In THP-1 cells, the RETN promoter with the G-A haplotype showed the highest activity. Nuclear proteins specifically recognized one base difference at SNP-358, but not at SNP-638. Therefore, A at -358 is required for G at −420 to confer the highest plasma resistin in the general Japanese population. In Caucasians, the association between SNP-420 and plasma resistin is not strong, and A at −358 may not exist, suggesting that SNP-358 could explain this ethnic difference. |
format | Text |
id | pubmed-2838794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-28387942010-03-19 A at Single Nucleotide Polymorphism-358 Is Required for G at -420 to Confer the Highest Plasma Resistin in the General Japanese Population Onuma, Hiroshi Tabara, Yasuharu Kawamura, Ryoichi Tanaka, Takashi Ohashi, Jun Nishida, Wataru Takata, Yasunori Ochi, Masaaki Yamada, Kazuya Kawamoto, Ryuichi Kohara, Katsuhiko Miki, Tetsuro Makino, Hideichi Osawa, Haruhiko PLoS One Research Article Insulin resistance is a feature of type 2 diabetes. Resistin, secreted from adipocytes, causes insulin resistance in mice. We previously reported that the G/G genotype of single nucleotide polymorphism (SNP) at −420 (rs1862513) in the human resistin gene (RETN) increased susceptibility to type 2 diabetes by enhancing its promoter activity. Plasma resistin was highest in Japanese subjects with G/G genotype, followed by C/G, and C/C. In this study, we cross-sectionally analyzed plasma resistin and SNPs in the RETN region in 2,019 community-dwelling Japanese subjects. Plasma resistin was associated with SNP-638 (rs34861192), SNP-537 (rs34124816), SNP-420, SNP-358 (rs3219175), SNP+299 (rs3745367), and SNP+1263 (rs3745369) (P<10(−13) in all cases). SNP-638, SNP -420, SNP-358, and SNP+157 were in the same linkage disequilibrium (LD) block. SNP-358 and SNP-638 were nearly in complete LD (r(2) = 0.98), and were tightly correlated with SNP-420 (r(2) = 0.50, and 0.51, respectively). The correlation between either SNP-358 (or SNP-638) or SNP-420 and plasma resistin appeared to be strong (risk alleles for high plasma resistin; A at SNP-358, r(2) = 0.5224, P = 4.94×10(−324); G at SNP-420, r(2) = 0.2616, P = 1.71×10(−133)). In haplotypes determined by SNP-420 and SNP-358, the estimated frequencies for C-G, G-A, and G-G were 0.6700, 0.2005, and 0.1284, respectively, and C-A was rare (0.0011), suggesting that subjects with A at −358, generally had G at −420. This G-A haplotype conferred the highest plasma resistin (8.24 ng/ml difference/allele compared to C-G, P<0.0001). In THP-1 cells, the RETN promoter with the G-A haplotype showed the highest activity. Nuclear proteins specifically recognized one base difference at SNP-358, but not at SNP-638. Therefore, A at -358 is required for G at −420 to confer the highest plasma resistin in the general Japanese population. In Caucasians, the association between SNP-420 and plasma resistin is not strong, and A at −358 may not exist, suggesting that SNP-358 could explain this ethnic difference. Public Library of Science 2010-03-16 /pmc/articles/PMC2838794/ /pubmed/20300528 http://dx.doi.org/10.1371/journal.pone.0009718 Text en Onuma et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Onuma, Hiroshi Tabara, Yasuharu Kawamura, Ryoichi Tanaka, Takashi Ohashi, Jun Nishida, Wataru Takata, Yasunori Ochi, Masaaki Yamada, Kazuya Kawamoto, Ryuichi Kohara, Katsuhiko Miki, Tetsuro Makino, Hideichi Osawa, Haruhiko A at Single Nucleotide Polymorphism-358 Is Required for G at -420 to Confer the Highest Plasma Resistin in the General Japanese Population |
title | A at Single Nucleotide Polymorphism-358 Is Required for G at -420 to Confer the Highest Plasma Resistin in the General Japanese Population |
title_full | A at Single Nucleotide Polymorphism-358 Is Required for G at -420 to Confer the Highest Plasma Resistin in the General Japanese Population |
title_fullStr | A at Single Nucleotide Polymorphism-358 Is Required for G at -420 to Confer the Highest Plasma Resistin in the General Japanese Population |
title_full_unstemmed | A at Single Nucleotide Polymorphism-358 Is Required for G at -420 to Confer the Highest Plasma Resistin in the General Japanese Population |
title_short | A at Single Nucleotide Polymorphism-358 Is Required for G at -420 to Confer the Highest Plasma Resistin in the General Japanese Population |
title_sort | at single nucleotide polymorphism-358 is required for g at -420 to confer the highest plasma resistin in the general japanese population |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838794/ https://www.ncbi.nlm.nih.gov/pubmed/20300528 http://dx.doi.org/10.1371/journal.pone.0009718 |
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