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Published in: Acta Diabetologica 4/2007

01-12-2007 | Original Article

Association of genetic variations near P2 promoter of the hepatocyte nuclear factor-4α gene and insulin secretion index in Thais

Authors: W. Jongjaroenprasert, S. Chanprasertyothin, A. Kongsuksai, P. Bunnag, G. Puavilai, B. Ongphiphadhanakul

Published in: Acta Diabetologica | Issue 4/2007

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Abstract

This study was aimed to assess the association of the two single nucleotide polymorphisms (SNPs) near P2 promoter (rs1884614 and rs2144908) of hepatocyte nuclear factor-4α (HNF4A) with insulin secretion index and type 2 diabetes in Thais. Participants were categorized into three groups; unrelated type 2 diabetes (N = 219), prediabetes subjects (N = 228), and normal glucose tolerant controls (N = 203). Homeostasis model assessment was calculated for individual insulin secretion and insulin sensitivity index. Genotyping of both SNPs was done by allele-specific PCR technique. Difference of SNP allele frequencies between groups were computed using the χ 2-statistic. Multivariate regression analysis was performed to determine the effect of SNPs on insulin secretion index. The clinical features of all groups were similar. We demonstrated genotype TT at rs1884614, BMI, and waist circumference were significantly associated with insulin secretion index (P = 0.023) but not with diabetes phenotype.
Literature
1.
go back to reference Aekplakorn W, Stolk RP, Neal B, Suriyawongpaisal P, Chongsuvivatwong V, Cheepudomwit S, Woodward M (2003) The prevalence and management of diabetes in Thai adults: the international collaborative study of cardiovascular disease in Asia. Diabetes Care 26:2758–2763PubMedCrossRef Aekplakorn W, Stolk RP, Neal B, Suriyawongpaisal P, Chongsuvivatwong V, Cheepudomwit S, Woodward M (2003) The prevalence and management of diabetes in Thai adults: the international collaborative study of cardiovascular disease in Asia. Diabetes Care 26:2758–2763PubMedCrossRef
2.
go back to reference Carlson CS, Eberle MA, Kruglyak L, Nickerson DA (2004) Mapping complex disease loci in whole-genome association studies. Nature 429:446–452PubMedCrossRef Carlson CS, Eberle MA, Kruglyak L, Nickerson DA (2004) Mapping complex disease loci in whole-genome association studies. Nature 429:446–452PubMedCrossRef
3.
go back to reference Chuang LM, Tsai ST, Huang BY, Tai TY (2002) The status of diabetes control in Asia-a cross-sectional survey of 24,317 patients with diabetes mellitus in 1998. Diabet Med 19:978–985PubMedCrossRef Chuang LM, Tsai ST, Huang BY, Tai TY (2002) The status of diabetes control in Asia-a cross-sectional survey of 24,317 patients with diabetes mellitus in 1998. Diabet Med 19:978–985PubMedCrossRef
4.
go back to reference Damcott CM, Hoppman N, Ott SH, Reinhart LJ, Wang J, Pollin TI, O’Connell JR, Mitchell BD, Shuldiner AR (2004) Polymorphisms in both promoters of hepatocyte nuclear factor 4-alpha are associated with type 2 diabetes in the Amish. Diabetes 53:3337–3341PubMedCrossRef Damcott CM, Hoppman N, Ott SH, Reinhart LJ, Wang J, Pollin TI, O’Connell JR, Mitchell BD, Shuldiner AR (2004) Polymorphisms in both promoters of hepatocyte nuclear factor 4-alpha are associated with type 2 diabetes in the Amish. Diabetes 53:3337–3341PubMedCrossRef
5.
go back to reference Davis TM, Pramukkul P, Suputtamongkol Y, Chaowagul W, Levy J (1995) Glucose tolerance in rural diabetic Thais, first-degree relatives and non-diabetic controls. Diabetes Res Clin Pract 27:171–180PubMedCrossRef Davis TM, Pramukkul P, Suputtamongkol Y, Chaowagul W, Levy J (1995) Glucose tolerance in rural diabetic Thais, first-degree relatives and non-diabetic controls. Diabetes Res Clin Pract 27:171–180PubMedCrossRef
6.
go back to reference Hansen SK, Rose CS, Glumer C, Drivsholm T, Borch-Johnsen K, Jorgensen T, Pedersen O, Hansen T (2005) Variation near the hepatocyte nuclear factor (HNF)-4alpha gene associates with type 2 diabetes in the Danish population. Diabetologia 48:452–458PubMedCrossRef Hansen SK, Rose CS, Glumer C, Drivsholm T, Borch-Johnsen K, Jorgensen T, Pedersen O, Hansen T (2005) Variation near the hepatocyte nuclear factor (HNF)-4alpha gene associates with type 2 diabetes in the Danish population. Diabetologia 48:452–458PubMedCrossRef
7.
go back to reference Kadowaki T, Miyake Y, Hagura R, Akanuma Y, Kajinuma H, Kuzuya N, Takaku F, Kosaka K (1984) Risk factors for worsening to diabetes in subjects with impaired glucose tolerance. Diabetologia 26:44–49PubMedCrossRef Kadowaki T, Miyake Y, Hagura R, Akanuma Y, Kajinuma H, Kuzuya N, Takaku F, Kosaka K (1984) Risk factors for worsening to diabetes in subjects with impaired glucose tolerance. Diabetologia 26:44–49PubMedCrossRef
8.
go back to reference Latorra D, Campbell K, Wolter A, Hurley JM (2003) Enhanced allele-specific PCR discrimination in SNP genotyping using 3′ locked nucleic acid (LNA) primers. Hum Mutat 22:79–85PubMedCrossRef Latorra D, Campbell K, Wolter A, Hurley JM (2003) Enhanced allele-specific PCR discrimination in SNP genotyping using 3′ locked nucleic acid (LNA) primers. Hum Mutat 22:79–85PubMedCrossRef
9.
go back to reference Levy JC, Matthews DR, Hermans MP (1998) Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 21:2191–2192PubMedCrossRef Levy JC, Matthews DR, Hermans MP (1998) Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 21:2191–2192PubMedCrossRef
10.
go back to reference Love-Gregory LD, Wasson J, Ma J, Jin CH, Glaser B, Suarez BK, Permutt MA (2004) A common polymorphism in the upstream promoter region of the hepatocyte nuclear factor-4 alpha gene on chromosome 20q is associated with type 2 diabetes and appears to contribute to the evidence for linkage in an Ashkenazi Jewish population. Diabetes 53:1134–1140PubMedCrossRef Love-Gregory LD, Wasson J, Ma J, Jin CH, Glaser B, Suarez BK, Permutt MA (2004) A common polymorphism in the upstream promoter region of the hepatocyte nuclear factor-4 alpha gene on chromosome 20q is associated with type 2 diabetes and appears to contribute to the evidence for linkage in an Ashkenazi Jewish population. Diabetes 53:1134–1140PubMedCrossRef
11.
go back to reference Odom DT, Zizlsperger N, Gordon DB, Bell GW, Rinaldi NJ, Murray HL, Volkert TL, Schreiber J, Rolfe PA, Gifford DK, Fraenkel E, Bell GI, Young RA (2004) Control of pancreas and liver gene expression by HNF transcription factors. Science 303:1378–1381PubMedCrossRef Odom DT, Zizlsperger N, Gordon DB, Bell GW, Rinaldi NJ, Murray HL, Volkert TL, Schreiber J, Rolfe PA, Gifford DK, Fraenkel E, Bell GI, Young RA (2004) Control of pancreas and liver gene expression by HNF transcription factors. Science 303:1378–1381PubMedCrossRef
12.
go back to reference Silander K, Mohlke KL, Scott LJ, Peck EC, Hollstein P, Skol AD, Jackson AU, Deloukas P, Hunt S, Stavrides G, Chines PS, Erdos MR, Narisu N, Conneely KN, Li C, Fingerlin TE, Dhanjal SK, Valle TT, Bergman RN, Tuomilehto J, Watanabe RM, Boehnke M, Collins FS (2004) Genetic variation near the hepatocyte nuclear factor-4 alpha gene predicts susceptibility to type 2 diabetes. Diabetes 53:1141–1149PubMedCrossRef Silander K, Mohlke KL, Scott LJ, Peck EC, Hollstein P, Skol AD, Jackson AU, Deloukas P, Hunt S, Stavrides G, Chines PS, Erdos MR, Narisu N, Conneely KN, Li C, Fingerlin TE, Dhanjal SK, Valle TT, Bergman RN, Tuomilehto J, Watanabe RM, Boehnke M, Collins FS (2004) Genetic variation near the hepatocyte nuclear factor-4 alpha gene predicts susceptibility to type 2 diabetes. Diabetes 53:1141–1149PubMedCrossRef
13.
go back to reference Thomas H, Jaschkowitz K, Bulman M, Frayling TM, Mitchell SM, Roosen S, Lingott-Frieg A, Tack CJ, Ellard S, Ryffel GU, Hattersley AT (2001) A distant upstream promoter of the HNF-4alpha gene connects the transcription factors involved in maturity-onset diabetes of the young. Hum Mol Genet 10:2089–2097PubMedCrossRef Thomas H, Jaschkowitz K, Bulman M, Frayling TM, Mitchell SM, Roosen S, Lingott-Frieg A, Tack CJ, Ellard S, Ryffel GU, Hattersley AT (2001) A distant upstream promoter of the HNF-4alpha gene connects the transcription factors involved in maturity-onset diabetes of the young. Hum Mol Genet 10:2089–2097PubMedCrossRef
14.
go back to reference Weedon MN, Owen KR, Shields B, Hitman G, Walker M, McCarthy MI, Love-Gregory LD, Permutt MA, Hattersley AT, Frayling TM (2004) Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population. Diabetes 53:3002–3006PubMedCrossRef Weedon MN, Owen KR, Shields B, Hitman G, Walker M, McCarthy MI, Love-Gregory LD, Permutt MA, Hattersley AT, Frayling TM (2004) Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population. Diabetes 53:3002–3006PubMedCrossRef
15.
Metadata
Title
Association of genetic variations near P2 promoter of the hepatocyte nuclear factor-4α gene and insulin secretion index in Thais
Authors
W. Jongjaroenprasert
S. Chanprasertyothin
A. Kongsuksai
P. Bunnag
G. Puavilai
B. Ongphiphadhanakul
Publication date
01-12-2007
Publisher
Springer Milan
Published in
Acta Diabetologica / Issue 4/2007
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-007-0008-5

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