Variation in the gene encoding Kruppel-like factor 7 influences body fat: studies of 14,818 Danes

Dorit Zobel; Camilla Andreasen; Kristoffer Burgdorf; Ehm Andersson; Annelli Sandbæk; Torsten Lauritzen; Knut Borch-Johnsen; Torben Jørgensen; Shiro Maeda; Yusuke Nakamura; Hans Eiberg; Oluf Pedersen; Torben Hansen

doi:10.1530/EJE-08-0688

Variation in the gene encoding Kruppel-like factor 7 influences body fat: studies of 14,818 Danes

Dorit Zobel, Camilla Andreasen, Kristoffer Burgdorf, Ehm Andersson, Annelli Sandbæk, Torsten Lauritzen, Knut Borch-Johnsen, Torben Jørgensen, Shiro Maeda, Yusuke Nakamura, Hans Eiberg, Oluf Pedersen, Torben Hansen

30 Citations (Scopus)

Abstract

Objective: KLF7 encodes Kruppel-like factor (KLF) 7, a member of the KLF family of transcription factors, initially shown to play important roles in cellular development and differentiation, and reported to be specifically involved in adipogenesis. Several single nucleotide polymorphisms (SNPs) have been identified in KLF7, of which the A-allele of rs2302870 has been associated with type 2 diabetes in a Japanese population; however, a possible association of KLF7 SNPs with obesity has not been investigated. We aimed to identify variation in the putative promoter region, the coding regions, exon/intron boundaries, and 3'-untranslated region of KLF7, and to examine identified variants in relation to obesity, type 2 diabetes and related quantitative traits in Danish individuals. Methods: Identified variants were investigated for association with type 2 diabetes in 8,777 individuals and with obesity in 14,818 individuals. Results: We identified four common SNPs in low pairwise linkage disequilibrium; three in the putative promoter region (-1119 G>A, -963 C>A [rs7568369], and -614 G>A) and IVS2+35092 A>C (rs2302870). We failed to confirm an association between rs2302870 and type 2 diabetes. Neither were rs7568369 associated with type 2 diabetes; however, the minor A-allele of rs7568369 protected against obesity (OR=0.90 [0.84-0.96], P=0.001) and in studies of quantitative traits (n=5,535) the variant associated with decreased BMI (P=0.002) and waist circumference (P=0.003). The -1119 G>A and -614 G>A variants were not associated with obesity or type 2 diabetes. Conclusion: We identified a novel association between the minor A-allele of KLF7 rs7568369 and protection against obesity in the Danish population.

Original language	English
Journal	European Journal of Endocrinology
Volume	160
Issue number	4
Pages (from-to)	603-9
ISSN	0804-4643
DOIs	https://doi.org/10.1530/EJE-08-0688
Publication status	Published - 2009

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Zobel, D., Andreasen, C., Burgdorf, K., Andersson, E., Sandbæk, A., Lauritzen, T., Borch-Johnsen, K., Jørgensen, T., Maeda, S., Nakamura, Y., Eiberg, H., Pedersen, O., & Hansen, T. (2009). Variation in the gene encoding Kruppel-like factor 7 influences body fat: studies of 14,818 Danes. European Journal of Endocrinology, 160(4), 603-9. https://doi.org/10.1530/EJE-08-0688

Zobel, D, Andreasen, C, Burgdorf, K, Andersson, E, Sandbæk, A, Lauritzen, T, Borch-Johnsen, K, Jørgensen, T, Maeda, S, Nakamura, Y, Eiberg, H , Pedersen, O & Hansen, T 2009, 'Variation in the gene encoding Kruppel-like factor 7 influences body fat: studies of 14,818 Danes', European Journal of Endocrinology, vol. 160, no. 4, pp. 603-9. https://doi.org/10.1530/EJE-08-0688

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title = "Variation in the gene encoding Kruppel-like factor 7 influences body fat: studies of 14,818 Danes",

abstract = "Objective: KLF7 encodes Kruppel-like factor (KLF) 7, a member of the KLF family of transcription factors, initially shown to play important roles in cellular development and differentiation, and reported to be specifically involved in adipogenesis. Several single nucleotide polymorphisms (SNPs) have been identified in KLF7, of which the A-allele of rs2302870 has been associated with type 2 diabetes in a Japanese population; however, a possible association of KLF7 SNPs with obesity has not been investigated. We aimed to identify variation in the putative promoter region, the coding regions, exon/intron boundaries, and 3'-untranslated region of KLF7, and to examine identified variants in relation to obesity, type 2 diabetes and related quantitative traits in Danish individuals. Methods: Identified variants were investigated for association with type 2 diabetes in 8,777 individuals and with obesity in 14,818 individuals. Results: We identified four common SNPs in low pairwise linkage disequilibrium; three in the putative promoter region (-1119 G>A, -963 C>A [rs7568369], and -614 G>A) and IVS2+35092 A>C (rs2302870). We failed to confirm an association between rs2302870 and type 2 diabetes. Neither were rs7568369 associated with type 2 diabetes; however, the minor A-allele of rs7568369 protected against obesity (OR=0.90 [0.84-0.96], P=0.001) and in studies of quantitative traits (n=5,535) the variant associated with decreased BMI (P=0.002) and waist circumference (P=0.003). The -1119 G>A and -614 G>A variants were not associated with obesity or type 2 diabetes. Conclusion: We identified a novel association between the minor A-allele of KLF7 rs7568369 and protection against obesity in the Danish population.",

author = "Dorit Zobel and Camilla Andreasen and Kristoffer Burgdorf and Ehm Andersson and Annelli Sandb{\ae}k and Torsten Lauritzen and Knut Borch-Johnsen and Torben J{\o}rgensen and Shiro Maeda and Yusuke Nakamura and Hans Eiberg and Oluf Pedersen and Torben Hansen",

year = "2009",

doi = "10.1530/EJE-08-0688",

language = "English",

volume = "160",

pages = "603--9",

journal = "European Journal of Endocrinology",

issn = "0804-4643",

publisher = "BioScientifica Ltd.",

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}

TY - JOUR

T1 - Variation in the gene encoding Kruppel-like factor 7 influences body fat: studies of 14,818 Danes

AU - Zobel, Dorit

AU - Andreasen, Camilla

AU - Burgdorf, Kristoffer

AU - Andersson, Ehm

AU - Sandbæk, Annelli

AU - Lauritzen, Torsten

AU - Borch-Johnsen, Knut

AU - Jørgensen, Torben

AU - Maeda, Shiro

AU - Nakamura, Yusuke

AU - Eiberg, Hans

AU - Pedersen, Oluf

AU - Hansen, Torben

PY - 2009

Y1 - 2009

N2 - Objective: KLF7 encodes Kruppel-like factor (KLF) 7, a member of the KLF family of transcription factors, initially shown to play important roles in cellular development and differentiation, and reported to be specifically involved in adipogenesis. Several single nucleotide polymorphisms (SNPs) have been identified in KLF7, of which the A-allele of rs2302870 has been associated with type 2 diabetes in a Japanese population; however, a possible association of KLF7 SNPs with obesity has not been investigated. We aimed to identify variation in the putative promoter region, the coding regions, exon/intron boundaries, and 3'-untranslated region of KLF7, and to examine identified variants in relation to obesity, type 2 diabetes and related quantitative traits in Danish individuals. Methods: Identified variants were investigated for association with type 2 diabetes in 8,777 individuals and with obesity in 14,818 individuals. Results: We identified four common SNPs in low pairwise linkage disequilibrium; three in the putative promoter region (-1119 G>A, -963 C>A [rs7568369], and -614 G>A) and IVS2+35092 A>C (rs2302870). We failed to confirm an association between rs2302870 and type 2 diabetes. Neither were rs7568369 associated with type 2 diabetes; however, the minor A-allele of rs7568369 protected against obesity (OR=0.90 [0.84-0.96], P=0.001) and in studies of quantitative traits (n=5,535) the variant associated with decreased BMI (P=0.002) and waist circumference (P=0.003). The -1119 G>A and -614 G>A variants were not associated with obesity or type 2 diabetes. Conclusion: We identified a novel association between the minor A-allele of KLF7 rs7568369 and protection against obesity in the Danish population.

AB - Objective: KLF7 encodes Kruppel-like factor (KLF) 7, a member of the KLF family of transcription factors, initially shown to play important roles in cellular development and differentiation, and reported to be specifically involved in adipogenesis. Several single nucleotide polymorphisms (SNPs) have been identified in KLF7, of which the A-allele of rs2302870 has been associated with type 2 diabetes in a Japanese population; however, a possible association of KLF7 SNPs with obesity has not been investigated. We aimed to identify variation in the putative promoter region, the coding regions, exon/intron boundaries, and 3'-untranslated region of KLF7, and to examine identified variants in relation to obesity, type 2 diabetes and related quantitative traits in Danish individuals. Methods: Identified variants were investigated for association with type 2 diabetes in 8,777 individuals and with obesity in 14,818 individuals. Results: We identified four common SNPs in low pairwise linkage disequilibrium; three in the putative promoter region (-1119 G>A, -963 C>A [rs7568369], and -614 G>A) and IVS2+35092 A>C (rs2302870). We failed to confirm an association between rs2302870 and type 2 diabetes. Neither were rs7568369 associated with type 2 diabetes; however, the minor A-allele of rs7568369 protected against obesity (OR=0.90 [0.84-0.96], P=0.001) and in studies of quantitative traits (n=5,535) the variant associated with decreased BMI (P=0.002) and waist circumference (P=0.003). The -1119 G>A and -614 G>A variants were not associated with obesity or type 2 diabetes. Conclusion: We identified a novel association between the minor A-allele of KLF7 rs7568369 and protection against obesity in the Danish population.

U2 - 10.1530/EJE-08-0688

DO - 10.1530/EJE-08-0688

M3 - Journal article

C2 - 19147600

SN - 0804-4643

VL - 160

SP - 603

EP - 609

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

IS - 4

ER -

Variation in the gene encoding Kruppel-like factor 7 influences body fat: studies of 14,818 Danes

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