A functional variant in the human betacellulin gene promoter is associated with type 2 diabetes
Betacellulin (BTC) plays an important role in differentiation, growth, and antiapoptosis of pancreatic beta-cells. We characterized about 2.3 kb of the 5'-flanking region of human BTC gene and identified six polymorphisms (-2159A>G, -1449G>A, -1388C>T, -279C>A, -233G>C, and -226A>G). The G allele in the -226A>G polymorphism was more frequent in type 2 diabetic patients (n = 250) than in nondiabetic subjects (n = 254) (35.6% vs. 27.8%, P = 0.007), and the -2159G, -1449A, and -1388T alleles were in complete linkage disequilibrium with the -226G allele. The frequencies of the -279A and -233C alleles were low (7.0 and 2.0% in diabetic patients), and no significant differences were observed. In the diabetic group, insulin secretion ability, assessed by the serum C-peptide response to intravenous glucagon stimulation, was lower in patients with the -226G allele (G/G, 2.96 +/- 0.16 ng/ml; G/A, 3.65 +/- 0.18 ng/ml; A/A, 3.99 +/- 0.16 ng/ml at 5 min after stimulation; P = 0.008). Furthermore, in vitro functional analyses indicated that both the -226G and the -233C alleles caused an approximately 50% decrease in the promoter activity, but no effects of the -2159A>G, -1449G>A, -1388C>T, and -279C>A polymorphisms were observed. These results suggest that the -226A/G polymorphism of the BTC gene may contribute to the development of diabetes.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2005 |
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| Erschienen: |
2005 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:54 |
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| Enthalten in: |
Diabetes - 54(2005), 12 vom: 01. Dez., Seite 3560-6 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nakano, Yoshio [VerfasserIn] |
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| Themen: |
5' Untranslated Regions |
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| Anmerkungen: |
Date Completed 11.09.2006 Date Revised 16.05.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM159109833 |
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| 041 | |a eng | ||
| 100 | 1 | |a Nakano, Yoshio |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A functional variant in the human betacellulin gene promoter is associated with type 2 diabetes |
| 264 | 1 | |c 2005 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
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| 500 | |a Date Completed 11.09.2006 | ||
| 500 | |a Date Revised 16.05.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Betacellulin (BTC) plays an important role in differentiation, growth, and antiapoptosis of pancreatic beta-cells. We characterized about 2.3 kb of the 5'-flanking region of human BTC gene and identified six polymorphisms (-2159A>G, -1449G>A, -1388C>T, -279C>A, -233G>C, and -226A>G). The G allele in the -226A>G polymorphism was more frequent in type 2 diabetic patients (n = 250) than in nondiabetic subjects (n = 254) (35.6% vs. 27.8%, P = 0.007), and the -2159G, -1449A, and -1388T alleles were in complete linkage disequilibrium with the -226G allele. The frequencies of the -279A and -233C alleles were low (7.0 and 2.0% in diabetic patients), and no significant differences were observed. In the diabetic group, insulin secretion ability, assessed by the serum C-peptide response to intravenous glucagon stimulation, was lower in patients with the -226G allele (G/G, 2.96 +/- 0.16 ng/ml; G/A, 3.65 +/- 0.18 ng/ml; A/A, 3.99 +/- 0.16 ng/ml at 5 min after stimulation; P = 0.008). Furthermore, in vitro functional analyses indicated that both the -226G and the -233C alleles caused an approximately 50% decrease in the promoter activity, but no effects of the -2159A>G, -1449G>A, -1388C>T, and -279C>A polymorphisms were observed. These results suggest that the -226A/G polymorphism of the BTC gene may contribute to the development of diabetes | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a 5' Untranslated Regions |2 NLM | |
| 650 | 7 | |a BTC protein, human |2 NLM | |
| 650 | 7 | |a Betacellulin |2 NLM | |
| 650 | 7 | |a Insulin |2 NLM | |
| 650 | 7 | |a Intercellular Signaling Peptides and Proteins |2 NLM | |
| 700 | 1 | |a Furuta, Hiroto |e verfasserin |4 aut | |
| 700 | 1 | |a Doi, Asako |e verfasserin |4 aut | |
| 700 | 1 | |a Matsuno, Shohei |e verfasserin |4 aut | |
| 700 | 1 | |a Nakagawa, Takayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Shimomura, Hiroko |e verfasserin |4 aut | |
| 700 | 1 | |a Sakagashira, Setsuya |e verfasserin |4 aut | |
| 700 | 1 | |a Horikawa, Yukio |e verfasserin |4 aut | |
| 700 | 1 | |a Nishi, Masahiro |e verfasserin |4 aut | |
| 700 | 1 | |a Sasaki, Hideyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Sanke, Tokio |e verfasserin |4 aut | |
| 700 | 1 | |a Nanjo, Kishio |e verfasserin |4 aut | |
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