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A variation in 3 ' ...
A variation in 3 ' UTR of hPTP1B increases specific gene expression and associates with insulin resistance
- Article/chapterEnglish2002
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LIBRIS-ID:oai:lup.lub.lu.se:b5610a8d-3bed-4276-ab4a-a13265391531
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https://lup.lub.lu.se/record/343595URI
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https://doi.org/10.1086/339270DOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Protein tyrosine phosphatase 1B (PTP1B) inhibits insulin signaling and, when overexpressed, plays a role in insulin resistance (Ahmad et al. 1997). We identified, in the 3' untranslated region of the PTP1B gene, a 1484insG variation that, in two different populations, is associated with several features of insulin resistance: among male individuals, higher values of the insulin resistance HOMA(IR) index (P = .006), serum triglycerides (P = .0002), and total/HDL cholesterol ratio (P = .025) and, among female individuals, higher blood pressure (P = .01). Similar data were also obtained in a family-based association study by use of sib pairs discordant for genotype (Gu et al. 2000). Subjects carrying the 1484insG variant showed also PTP1B mRNA overexpression in skeletal muscle (6,166 +/- 1,879 copies/40 ng RNA vs. 2,983 +/- 1,620;). Finally, PTP1B mRNA stability was significantly higher (P < .01) in human embryo kidney 293 cells transfected with 1484insG PTP1B, as compared with those transfected with wild-type PTP1B. Our data indicate that the 1484insG allele causes PTP1B overexpression and plays a role in insulin resistance. Therefore, individuals carrying the 1484insG variant might particularly benefit from PTP1B inhibitors, a promising new tool for treatment of insulin resistance (Kennedy and Ramachandran 2000).
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Frittitta, L
(author)
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Miscio, G
(author)
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Bozzali, M
(author)
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Baratta, R
(author)
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Centra, M
(author)
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Spampinato, D
(author)
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Santagati, MG
(author)
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Ercolino, T
(author)
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Cisternino, C
(author)
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Soccio, T
(author)
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Mastroianno, S
(author)
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Tassi, V
(author)
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Almgren, PeterLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-pal
(author)
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Pizzuti, A
(author)
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Vigneri, R
(author)
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Trischitta, V
(author)
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Genomik, diabetes och endokrinologiForskargrupper vid Lunds universitet
(creator_code:org_t)
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In:American Journal of Human Genetics: Elsevier BV70:3, s. 806-8120002-9297
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Di Paola, R
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Frittitta, L
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Miscio, G
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Bozzali, M
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Baratta, R
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Centra, M
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Spampinato, D
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Santagati, MG
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Ercolino, T
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Cisternino, C
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Soccio, T
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Mastroianno, S
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Tassi, V
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Almgren, Peter
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Pizzuti, A
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Vigneri, R
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Trischitta, V
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- MEDICAL AND HEALTH SCIENCES
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and Basic Medicine
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and Medical Genetics
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Lund University