In a recent genome-wide association study, the zinc finger, C3HC-type containing 1 (ZC3HC1) polymorphism was strongly associated with coronary artery disease (CAD) by an unknown mechanism. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is related with CAD through low-density lipoprotein (LDL) metabolism. The association of both of the above genetic variants with hypertension was studied in a Finnish 50-year-old cohort.A total of 325 hypertensive cases and 444 nonhypertensive controls were obtained from the Tampere adult population cardiovascular risk study. Samples were genotyped for ZC3HC1 rs11556924 and PCSK9 rs11206510 polymorphisms using Competitive Allele Specific PCR technique. A subpopulation that had available follow-up data from ages of 40, 45, and 50 years was also analyzed.ZC3HC1 rs11556924 (C > T) genotype CC was associated with hypertension compared with the T-allele carriers (P = 0.013). PCSK9 rs11206510 (T > C) genotype was not associated with hypertension. Its major TT-genotype was associated with higher total cholesterol (P = 0.044) and LDL (P = 0.029) compared with the C-allele.We report for the first time that ZC3HC1 rs11556924 was associated with essential hypertension in 50-year-old patients. Although PCSK9 rs11206510 was not associated with hypertension, our study confirms its association with serum cholesterol levels.

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  • Despite similar overall expression of ZC3HC1 in blood, the protective variant (His363) shows increased phosphorylation and higher protein levels than the risk variant (Arg363).
  • The His363 variant leads to greater nuclear mobility and reduced cell growth in HeLa cells, which suggests its potential role in influencing cell proliferation related to atherosclerosis.
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