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Resequencing PNMT in European hypertensive and normotensive individuals: no common susceptibilily variants for hypertension and purifying selection on intron 1.

ABSTRACT: Human linkage and animal QTL studies have indicated the contribution of genes on Chr17 into blood pressure regulation. One candidate gene is PNMT, coding for phenylethanolamine-N-methyltransferase, catalyzing the synthesis of epinephrine from norepinephrine.Fine-scale variation of PNMT was screened by resequencing hypertensive (n = 50) and normotensive (n = 50) individuals from two European populations (Estonians and Czechs). The resulting polymorphism data were analyzed by statistical genetics methods using Genepop 3.4, PHASE 2.1 and DnaSP 4.0 software programs. In silico prediction of transcription factor binding sites for intron 1 was performed with MatInspector 2.2 software.PNMT was characterized by minimum variation and excess of rare SNPs in both normo- and hypertensive individuals. None of the SNPs showed significant differences in allelic frequencies among population samples, as well as between screened hypertensives and normotensives. In the joint case-control analysis of the Estonian and the Czech samples, hypertension patients had a significant excess of heterozygotes for two promoter region polymorphisms (SNP-184; SNP-390). The identified variation pattern of PNMT reflects the effect of purifying selection consistent with an important role of PNMT-synthesized epinephrine in the regulation of cardiovascular and metabolic functions, and as a CNS neurotransmitter. A striking feature is the lack of intronic variation. In silico analysis of PNMT intron 1 confirmed the presence of a human-specific putative Glucocorticoid Responsive Element (GRE), inserted by Alu-mediated transfer. Further analysis of intron 1 supported the possible existence of a full Glucocorticoid Responsive Unit (GRU) predicted to consist of multiple gene regulatory elements known to cooperate with GRE in driving transcription. The role of these elements in regulating PNMT expression patterns and thus determining the dynamics of the synthesis of epinephrine is still to be studied.We suggest that the differences in PNMT expression between normotensives and hypertensives are not determined by the polymorphisms in this gene, but rather by the interplay of gene expression regulators, which may vary among individuals. Understanding the determinants of PNMT expression may assist in developing PNMT inhibitors as potential novel therapeutics.

SUBMITTER: Kepp K

PROVIDER: S-EPMC1947951 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature

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Resequencing PNMT in European hypertensive and normotensive individuals: no common susceptibilily variants for hypertension and purifying selection on intron 1.

Kepp Katrin K Juhanson Peeter P Kozich Viktor V Ots Mai M Viigimaa Margus M Laan Maris M

BMC medical genetics 20070723

<h4>Background</h4>Human linkage and animal QTL studies have indicated the contribution of genes on Chr17 into blood pressure regulation. One candidate gene is PNMT, coding for phenylethanolamine-N-methyltransferase, catalyzing the synthesis of epinephrine from norepinephrine.<h4>Methods</h4>Fine-scale variation of PNMT was screened by resequencing hypertensive (n = 50) and normotensive (n = 50) individuals from two European populations (Estonians and Czechs). The resulting polymorphism data wer ...[more]

PMID: 17645789

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Project description:BackgroundHypertension is the major public health concern; leading to cardiovascular disease. It is associated with alteration in hematological parameters which may lead to end-organ damage. Thus, this study aimed to compare hematological parameters between hypertensive and normotensive adult groups in Harar, eastern Ethiopia.MethodsA comparative cross-sectional study was conducted from January to March, 2020 at Jugel and Hiwotfana Specialized University hospital, Harar, eastern Ethiopia. Convenient sampling technique was used to recruit 102 hypertensive patients from the two hospitals and 102 apparently healthy blood donors. Participant's socio-demographic and clinical information were collected using pre-tested structured questionnaire. Blood sample were collected and analyzed by Beckman Coulter DxH 500 analyzer for complete blood count. The data were entered and analyzed using SPSS version 23. Independent t-test and Mann Whitney u-test was used for comparison between groups. Spearman's correlation was used for correlation test. P values less than 0.05 was considered as statistically significant.Result102 hypertensive and 102 healthy controls were enrolled in this study. The median ± IQR value of white blood cell (WBC) count, hemoglobin (Hgb), hematocrit (HCT), red cell distribution width (RDW) and mean platelet volume (MPV) were significantly higher in hypertensive group compared to apparently healthy control group. Additionally, RBC (red blood cell) count, HCT and RDW showed statistically significant positive correlations with systolic and diastolic blood pressure. WBC count and RDW were significantly and positively correlated with body mass index (BMI). Platelet (PLT) count had a significant but negative correlation (r = -0.219, P = 0.027) with duration of hypertension illness while MPV showed positive and significant correlation (r = 0.255, P = 0.010).ConclusionThe median values of WBC, Hgb, HCT, RDW and MPV were significantly higher in hypertensive patient compared to apparently healthy individuals. Hence, it is important to assess hematological parameters for hypertensive individuals which may help to prevent complications associated with hematological aberrations. However, further studies are required to understand hypertensive associated changes in hematological parameters.

Dataset Information

Resequencing PNMT in European hypertensive and normotensive individuals: no common susceptibilily variants for hypertension and purifying selection on intron 1.

Publications

Resequencing PNMT in European hypertensive and normotensive individuals: no common susceptibilily variants for hypertension and purifying selection on intron 1.

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