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Journal of Lipid Research, Vol. 47, 944-952, May 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Zinc Finger Protein 202, genetic variation, and HDL cholesterol in the general population

Maria C. Stene^*, Ruth Frikke-Schmidt^*, Børge G. Nordestgaard^, and Anne Tybjærg-Hansen^1,*,

^* Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Department of Clinical Biochemistry, Herlev University Hospital, Copenhagen, Denmark
Copenhagen City Heart Study, Bispebjerg University Hospital, Copenhagen, Denmark

Published, JLR Papers in Press, February 7, 2006.

¹ To whom correspondence should be addressed. e-mail: at-h{at}rh.dk

Zinc Finger Protein 202 (ZNF202) is a transcriptional repressor that binds elements found predominantly in genes involved in HDL metabolism. We tested the following hypotheses: 1) frequencies of single-nucleotide polymorphisms (SNPs) and haplotypes in ZNF202 differ between individuals with low and high HDL cholesterol; and 2) SNPs in ZNF202 affect HDL cholesterol levels in the general population. We screened the promoter and protein-coding exons of ZNF202 in individuals with the highest 1% (n = 95) and lowest 1% (n = 95) HDL cholesterol among 9,259 Danish adults. None of the 10 SNPs identified differed in frequency as single sites or as haplotypes between low and high HDL cholesterol groups. In accordance with this, seven mutations were equally frequent (4–5%) in individuals with low or high HDL cholesterol. Finally, for all five SNPs identified in the coding region, we determined the association of genotype with HDL cholesterol in 9,259 individuals from the general population. Four SNPs were not associated with variation in HDL cholesterol, although c.*2T>G homozygosity was associated with a discrete effect on HDL cholesterol in men. We show that genetic variation in ZNF202 is common in the general population. However, SNPs in the protein-coding region of ZNF202 do not make a major contribution to HDL cholesterol levels.

Supplementary key words apolipoproteins • genetic epidemiology • large-scale genotyping • lipids • lipoproteins • molecular biology • molecular medicine • reverse cholesterol transport • transcription factors • high density lipoprotein cholesterol

Abbreviations: apoA-I, apolipoprotein A-I; BMI, body mass index; KRAB, Krüppel-associated box; LD, linkage disequilibrium; SCAN, SRE-ZBP, CT-finS1, AW-1, Number 18; SNP, single-nucleotide polymorphism; UTR, untranslated region; ZNF202, Zinc Finger Protein 202

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