Population-based resequencing of LIPG and ZNF202 genes in subjects with extreme HDL levels

Abstract

Endothelial lipase (LIPG) and zinc finger protein 202 (ZNF202) 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 highorlowHDL-C levels. The selected subjects were 141 Whites (High HDL Group: n = 68, x̄ = 76.90mg/dl; Low HDL Group: n = 73, x̄ = 32.55mg/dl) and 94 Hispan-ics (High HDL Group: n = 46, x̄ = 74.85mg/dl; Low HDL Group: n = 48, x̄ = 29.95mg/dl). We identified a total of 185 and 122 sequence variants in LIPG and ZNF202, respectively. We found only two missense variants in LIPG (T111 I and N396S) and two in ZNF202 (A154V and K259E). In both genes, there were several variants unique to either the low or high HDL group. For LIPG, the proportion of unique variants differed between the high and low HDL groups in both Whites (p = 0.022) and Hispanics (p= 0.017), but for ZNF202 this difference was observed only in Hispanics (p = 0.021). We also identified a common haplo-type in ZNF202 among Whites that was significantly associated with the high HDL group (p = 0.013). These findings provide insights into the genetics of LIPG and ZNF202, 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. © 2012 Razzaghi, Santorico and Kamboh.