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

¹ Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Copenhagen, Denmark² Department of General Practice, University of Aarhus, Aarhus, DK-8000 Denmark³ Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark⁴ Faculty of Health Science, University of Aarhus, Aarhus, Denmark⁵ Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan⁶ Institute of Medical Biochemistry and Genetics, University of Copenhagen, Copenhagen, Denmark⁷ Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark⁸ Faculty of Health Science, University of Southern Denmark, Odense, Denmark

(Correspondence should be addressed to D P Zobel; Email: dpaj{at}steno.dk)

Objective: KLF7 encodes Krüppel-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'-UTR 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 8777 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 was 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 body mass index (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.