AUTHOR=Razzaghi Hamid , Santorico Stephanie A., Kamboh M I.

TITLE=Population-Based Resequencing of LIPG and ZNF202 Genes in Subjects with Extreme HDL Levels

JOURNAL=Frontiers in Genetics

VOLUME=3

YEAR=2012

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2012.00089

DOI=10.3389/fgene.2012.00089

ISSN=1664-8021

ABSTRACT=<p>Endothelial lipase (<italic>LIPG</italic>) and zinc finger protein 202 (<italic>ZNF202</italic>) are two pivotal genes in high density lipoprotein (HDL metabolism). We sought to determine their genetic contribution to variation in HDL-cholesterol levels by comprehensive resequencing of both genes in 235 individuals with high or low HDL-C levels. The selected subjects were 141 Whites (High HDL Group: <italic>n</italic> = 68, <inline-formula><mml:math id="M1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mrow><mml:mi>x</mml:mi></mml:mrow><mml:mo class="MathClass-op">̄</mml:mo></mml:mover><mml:mo class="MathClass-rel">=</mml:mo><mml:mn>76</mml:mn><mml:mo class="MathClass-punc">.</mml:mo><mml:mn>90</mml:mn><mml:mspace width="0.3em" class="thinspace" /><mml:mstyle class="text"><mml:mtext>mg/dl;</mml:mtext></mml:mstyle></mml:mrow></mml:math></inline-formula> Low HDL Group: <italic>n</italic> = 73, <inline-formula><mml:math id="M2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mrow><mml:mi>x</mml:mi></mml:mrow><mml:mo class="MathClass-op">̄</mml:mo></mml:mover><mml:mo class="MathClass-rel">=</mml:mo><mml:mn>32</mml:mn><mml:mo class="MathClass-punc">.</mml:mo><mml:mn>55</mml:mn><mml:mspace width="0.3em" class="thinspace" /><mml:mstyle class="text"><mml:mtext>mg/dl</mml:mtext></mml:mstyle></mml:mrow></mml:math></inline-formula>) and 94 Hispanics (High HDL Group: <italic>n</italic> = 46, <inline-formula><mml:math id="M3" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mrow><mml:mi>x</mml:mi></mml:mrow><mml:mo class="MathClass-op">̄</mml:mo></mml:mover><mml:mo class="MathClass-rel">=</mml:mo><mml:mn>74</mml:mn><mml:mo class="MathClass-punc">.</mml:mo><mml:mn>85</mml:mn><mml:mspace width="0.3em" class="thinspace" /><mml:mstyle class="text"><mml:mtext>mg/dl;</mml:mtext></mml:mstyle></mml:mrow></mml:math></inline-formula> Low HDL Group: <italic>n</italic> = 48, <inline-formula><mml:math id="M4" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mrow><mml:mi>x</mml:mi></mml:mrow><mml:mo class="MathClass-op">̄</mml:mo></mml:mover><mml:mo class="MathClass-rel">=</mml:mo><mml:mn>29</mml:mn><mml:mo class="MathClass-punc">.</mml:mo><mml:mn>95</mml:mn><mml:mspace width="0.3em" class="thinspace" /><mml:mstyle class="text"><mml:mtext>mg/dl</mml:mtext></mml:mstyle></mml:mrow></mml:math></inline-formula>). We identified a total of 185 and 122 sequence variants in <italic>LIPG</italic> and <italic>ZNF202</italic>, respectively. We found only two missense variants in <italic>LIPG</italic> (T111I and N396S) and two in <italic>ZNF202</italic> (A154V and K259E). In both genes, there were several variants unique to either the low or high HDL group. For <italic>LIPG</italic>, the proportion of unique variants differed between the high and low HDL groups in both Whites (<italic>p</italic> = 0.022) and Hispanics (<italic>p</italic> = 0.017), but for <italic>ZNF202</italic> this difference was observed only in Hispanics (<italic>p</italic> = 0.021). We also identified a common haplotype in <italic>ZNF202</italic> among Whites that was significantly associated with the high HDL group (<italic>p</italic> = 0.013). These findings provide insights into the genetics of <italic>LIPG</italic> and <italic>ZNF202</italic>, and suggest that sequence variants occurring with high frequency in non-exonic regions may play a prominent role in modulating HDL-C levels in the general population.</p>