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Non-synonymous single-nucleotide polymorphisms associated with blood pressure and hypertension.

Hong, KW; Jin, HS; Lim, JE; Cho, YS; Go, MJ; Jung, J; Lee, JE; Choi, J; Shin, C; Hwang, SY; Lee, SH; Park, HK; Oh, B
Journal of human hypertension, 24(11):763-774, 2010
Journal Title
Journal of human hypertension
In this study, we determined the association of 1180 non-synonymous single-nucleotide polymorphisms (SNPs) with systolic blood pressure (SBP) and hypertensive status. A total of 8842 subjects were taken from two community-based cohorts--Ansung (n=4183) and Ansan (n=4659), South Korea--which had been established for genome-wide association studies (GWAS). Five SNPs (rs16835244, rs2286672, rs6265, rs17237198 and rs7312017) were significantly associated (P-values: 0.003-0.0001, not corrected for genome-wide significance) with SBP in both cohorts. Of these SNPs, rs16835244 and rs2286672 correlated with risk for hypertension. The rs16835244 SNP replaces Ala288 in arginine decarboxylase (ADC) with serine, and rs2286672 replaces Arg172 in phospholipase D2 (PLD2) with cysteine. A comparison of peptide sequences between vertebrate homologues revealed that the SNPs identified occur at conserved amino-acid residues. In silico analysis of the protein structure showed that the substitution of a polar residue, serine, for a non-polar alanine at amino-acid residue 288 affects a conformational change in ADC, and that Arg172 in PLD2 resides in the PX domain, which is important for membrane trafficking. These results provide insights into the function of these non-synonymous SNPs in the development of hypertension. The study investigating non-synonymous SNPs from GWAS not only by statistical association analysis but also by biological relevance through the protein structure might be a good approach for identifying genetic risk factors for hypertension, in addition to discovering causative variations.
MeSH terms
AdultAgedAmino Acid SequenceAsian Continental Ancestry Group/geneticsBlood Pressure/*geneticsCase-Control StudiesChi-Square DistributionFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansHypertension/ethnology/*genetics/physiopathologyLinear ModelsMaleMiddle AgedModels, MolecularMolecular Sequence DataOdds RatioPhenotype*Polymorphism, Single NucleotideProtein ConformationRepublic of Korea/epidemiologyRisk AssessmentRisk FactorsStructure-Activity Relationship
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Journal Papers > School of Medicine / Graduate School of Medicine > Medical Genetics
AJOU Authors
진, 현석
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