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

Maria C Stene,Ruth Frikke-Schmidt,Børge G Nordestgaard,Anne Tybjærg-Hansen

doi:10.1194/jlr.m500521-jlr200

Maria C Stene, Ruth Frikke-Schmidt + Show 2 more

Open Access

https://doi.org/10.1194/jlr.m500521-jlr200

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Abstract

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.

Highlights

Zinc Finger Protein 202 (ZNF202) is a transcriptional repressor that binds elements found predominantly in genes involved in HDL metabolism
ZNF202 target genes are mainly involved in lipid and, HDL cholesterol metabolism [10,11,12], suggesting that this transcriptional repressor might be important in the determination of HDL cholesterol levels in the general population
With the aim to identify genetic variation in ZNF202 affecting HDL cholesterol levels in the general population, we used a systematic approach in which we screened 700 bp of the promoter and all protein-coding exons of the ZNF202 gene in 190 individuals with extreme HDL cholesterol levels selected from a large sample of the general population (n 5 9,259)

Summary

Introduction

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 levels; and 2) SNPs in the protein-coding region of ZNF202 affect HDL cholesterol levels in the general population. To increase the likelihood of identifying genetic variation with significant effects on HDL cholesterol levels, we screened the promoter and protein coding regions of ZNF202 (z2 kb) in 95 individuals with the 1% lowest and in 95 individuals with the 1% highest HDL cholesterol levels for age and gender from a general population sample, the Copenhagen City Heart Study (n 5 9,259). All SNPs identified in and around the protein-coding region were genotyped in the entire general population sample, and the effect on HDL cholesterol and apolipoprotein A-I (apoA-I) levels was determined

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