scholarly journals Evidence of a Role for One-Carbon Metabolism in Blood Pressure: Can B Vitamin Intervention Address the Genetic Risk of Hypertension Owing to a Common Folate Polymorphism?

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Helene McNulty ◽  
J J Strain ◽  
Catherine F Hughes ◽  
Kristina Pentieva ◽  
Mary Ward
Keyword(s):  
Blood Pressure ◽  
Carbon Metabolism ◽  
Genetic Risk ◽  
Methylenetetrahydrofolate Reductase ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Hypertension In Pregnancy ◽  
Increased Risk ◽  
One Carbon Metabolism ◽  
In Pregnancy

ABSTRACT Hypertension in adulthood is recognized as the leading risk factor contributing to mortality worldwide, primarily from cardiovascular disease, whereas hypertension in pregnancy leads to serious adverse fetal and maternal outcomes. This article explores the under-recognized role of one-carbon metabolism in blood pressure (BP) and the potential for folate-related B vitamins to protect against hypertension. Genome-wide association studies and clinical studies provide evidence linking the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with BP and increased risk of hypertension and hypertension in pregnancy. A novel role for riboflavin (the MTHFR cofactor) has recently emerged, however, with evidence from randomized trials that supplemental riboflavin can lower BP specifically in adults with the variant MTHFR 677TT genotype. Further studies are required to elucidate the biological mechanisms linking one-carbon metabolism with BP and explore the effect of riboflavin in modulating the genetic risk of hypertension in early and later life.

scholarly journals Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Mary Ward ◽  
Catherine F. Hughes ◽  
J. J. Strain ◽  
Rosie Reilly ◽  
Conal Cunningham ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Genetic Risk ◽  
Antihypertensive Treatment ◽  
Methylenetetrahydrofolate Reductase ◽  
Randomised Trial ◽  
Population Based ◽  
Nutrition Survey ◽  
Increased Risk ◽  
The Impact ◽  
Riboflavin Status

Abstract Background Genome-wide and clinical studies have linked the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with hypertension, whilst limited evidence shows that intervention with riboflavin (i.e. the MTHFR co-factor) can lower blood pressure (BP) in hypertensive patients with the variant MTHFR 677TT genotype. We investigated the impact of this common polymorphism on BP throughout adulthood and hypothesised that riboflavin status would modulate the genetic risk of hypertension. Methods Observational data on 6076 adults of 18–102 years were drawn from the Joint Irish Nutrigenomics Organisation project, comprising the Trinity-Ulster Department of Agriculture (TUDA; volunteer sample) and the National Adult Nutrition Survey (NANS; population-based sample) cohorts. Participants were recruited from the Republic of Ireland and Northern Ireland (UK) in 2008–2012 using standardised methods. Results The variant MTHFR 677TT genotype was identified in 12% of adults. From 18 to 70 years, this genotype was associated with an increased risk of hypertension (i.e. systolic BP ≥ 140 and/or a diastolic BP ≥ 90 mmHg): odds ratio (OR) 1.42, 95% confidence interval (CI) 1.07 to 1.90; P = 0.016, after adjustment for antihypertensive drug use and other significant factors, namely, age, male sex, BMI, alcohol and total cholesterol. Low or deficient biomarker status of riboflavin (observed in 30.2% and 30.0% of participants, respectively) exacerbated the genetic risk of hypertension, with a 3-fold increased risk for the TT genotype in combination with deficient riboflavin status (OR 3.00, 95% CI, 1.34–6.68; P = 0.007) relative to the CC genotype combined with normal riboflavin status. Up to 65 years, we observed poorer BP control rates on antihypertensive treatment in participants with the TT genotype (30%) compared to those without this variant, CT (37%) and CC (45%) genotypes (P < 0.027). Conclusions The MTHFR 677TT genotype is associated with higher BP independently of homocysteine and predisposes adults to an increased risk of hypertension and poorer BP control with antihypertensive treatment, whilst better riboflavin status is associated with a reduced genetic risk. Riboflavin intervention may thus offer a personalised approach to prevent the onset of hypertension in adults with the TT genotype; however, this requires confirmation in a randomised trial in non-hypertensive adults.

scholarly journals High blood pressure in pregnancy // Hipertenzija u trudnoći

2018 ◽  
Vol 5 (1) ◽  
pp. 28
Author(s):  
Marijana Bucalo ◽  
Anastasija Stojšić Milosavljević ◽  
Bojana Babin
Keyword(s):  
Blood Pressure ◽  
Literature Review ◽  
High Blood Pressure ◽  
Gestational Hypertension ◽  
Morbidity And Mortality ◽  
Significant Problem ◽  
Hypertension In Pregnancy ◽  
Gynecology And Obstetrics ◽  
Increased Risk ◽  
In Pregnancy

High blood pressure in pregnancy is a significant problem and has long been causing the attention of perinatologists. Hypertensive disorders in pregnancy are the leading cause of morbidity and mortality of mothers and fetuses. About 8% of pregnancies complicate high blood pressure. It is estimated that 192 women die daily due to hypertensive complications during pregnancy. Hypertension in pregnancy is not a single entity but it includes: pre-existing hypertension; gestational hypertension; pre-pregnancy existing hypertension complicated by gestational hypertension with proteinuria; prenatally unclassified hypertension. The aim of this paper is to point to the problem of hypertension in pregnancy and the importance of its early detection.It’s a literature review. The literature review period is from 2003-2013. The literature review was carried out in the Hinari, Pubmed and Google Scholar databases.A total of 50 scientific and professional papers in English and Serbian have been examined, of which work is included. 17. By reviewing the summary of each paper, all articles that did not report hypertension in pregnancy were excluded. Through research that was conducted, it was concluded that pregnancy is a significant problem in pregnancy and is therefore the leading cause of morbidity and mortality of both mothers and fetuses. However, the decision to introduce antihypertensive therapy and the choice of an adequate drug during pregnancy should be based on the assessment of the benefits and risks for each pregnant woman individually. Thus, the role of the health care nurse in gynecology and obstetrics has the primary goal and task to preserve and improve the health of women through a series of preventive-promotional activities, all of which are covered through primary, secondary, and tertiary prevention.A literature review lists the risk factors that can cause hypertension in pregnancy, including: age of the patient - under 20 and over 35 years, vascular and renal pathology, gestational diabetes, obesity or malnutrition, pheochromocytoma, systemic lupus, poor living conditions, there is and increased risk in first-born patients. Women who have been hypertensive during their first pregnancy have a higher risk of subsequent pregnancy.

scholarly journals The Genetic Architecture of Gliomagenesis–Genetic Risk Variants Linked to Specific Molecular Subtypes

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2001 ◽  
Author(s):  
Wendy Yi-Ying Wu ◽  
Gunnar Johansson ◽  
Carl Wibom ◽  
Thomas Brännström ◽  
Annika Malmström ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Molecular Subtypes ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Molecular Alterations ◽  
Risk Variants ◽  
Genome Wide ◽  
Increased Risk ◽  
Genetic Risk Variants

Genome-wide association studies have identified 25 germline genetic loci that increase the risk of glioma. The somatic tumor molecular alterations, including IDH-mutation status and 1p/19q co-deletion, have been included into the WHO 2016 classification system for glioma. To investigate how the germline genetic risk variants correlate with the somatic molecular subtypes put forward by WHO, we performed a meta-analysis that combined findings from 330 Swedish cases and 876 controls with two other recent studies. In total, 5,103 cases and 10,915 controls were included. Three categories of associations were found. First, variants in TERT and TP53 were associated with increased risk of all glioma subtypes. Second, variants in CDKN2B-AS1, EGFR, and RTEL1 were associated with IDH-wildtype glioma. Third, variants in CCDC26 (the 8q24 locus), C2orf80 (close to IDH), LRIG1, PHLDB1, ETFA, MAML2 and ZBTB16 were associated with IDH-mutant glioma. We therefore propose three etiopathological pathways in gliomagenesis based on germline variants for future guidance of diagnosis and potential functional targets for therapies. Future prospective clinical trials of patients with suspicion of glioma diagnoses, using the genetic variants as biomarkers, are necessary to disentangle how strongly they can predict glioma diagnosis.

Abstract 238: Genetic Risk Score as a Predictor of Incident Hypertension and Blood Pressure Change Over Time

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Teemu Niiranen ◽  
Juhani Mäki ◽  
Aki S Havulinna ◽  
Veikko Salomaa ◽  
Antti Jula
Keyword(s):  
Blood Pressure ◽  
Genetic Risk ◽  
Odds Ratio ◽  
Association Studies ◽  
Genetic Risk Score ◽  
Genome Wide Association Studies ◽  
Prevalence Odds Ratio ◽  
Change Over Time ◽  
Incident Hypertension ◽  
Over Time

Little data exist regarding single nucleotide polymorphisms (SNPs) predicting blood pressure (BP) change over time. We genotyped 32 common SNPs in a nationwide cohort aged ≥30 years examined in years 2000 (n=5402) and 2011 (n=3373). We investigated whether genetic risk scores (GRSs) constructed of these variants would predict incident hypertension and BP change over time. We created GRSs for systolic and diastolic BP by multiplying the risk allele count of each SNP by the effect size estimated in published genome-wide association studies. In linear and logistic regression models adjusted for traditional risk factors, 1-unit increases in GRSs were associated with higher systolic and diastolic BP values both at baseline (β±SE, 1.04±0.14 mmHg and 1.11±0.13 mmHg; P<0.0001 for both) and at reinvestigation (β±SE, 0.86±0.18 mmHg and 0.74±0.16 mm Hg; P<0.0001 for both) and with increased hypertension prevalence (odds ratio [95% CI], 1.12 [1.08-1.16] and 1.18 [1.11-1.26]; P<0.0001 for both). Among all participants who were normotensive at baseline and participated in the re-examination (n=2045), the GRSs were not independently associated with BP change over time (β±SE, 0.016±0.18 mmHg and 0.019±0.18 mmHg; P≥0.27 for both). However, in the top tertile of the GRS, the predicted increase in BP compared with the bottom tertile was 1.59±0.78 mmHg greater for systolic BP (P=0.04) and 0.79±0.49 mmHg greater for diastolic BP (P=0.11) and the odds ratio for incident hypertension was 30% higher (P=0.04). Our data show that GRSs are strongly associated with BP and prevalence of hypertension, but only weakly associated with BP increase and incidence of hypertension in a general adult population.

scholarly journals Association Between Genetic Variation in Blood Pressure and Increased Lifetime Risk of Peripheral Artery Disease

2021 ◽  
Author(s):  
Michael G. Levin ◽  
Derek Klarin ◽  
Venexia M. Walker ◽  
Dipender Gill ◽  
Julie Lynch ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Peripheral Artery Disease ◽  
Pulse Pressure ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Artery Disease

Objective: We aimed to estimate the effect of blood pressure (BP) traits and BP-lowering medications (via genetic proxies) on peripheral artery disease. Approach and Results: Genome-wide association studies summary statistics were obtained for BP, peripheral artery disease (PAD), and coronary artery disease. Causal effects of BP on PAD were estimated by 2-sample Mendelian randomization using a range of pleiotropy-robust methods. Increased systolic BP (SBP), diastolic BP, mean arterial pressure (MAP), and pulse pressure each significantly increased risk of PAD (SBP odds ratio [OR], 1.20 [1.16–1.25] per 10 mm Hg increase, P =1×10 −24 ; diastolic BP OR, 1.27 [1.18–1.35], P =4×10 − 11 ; MAP OR, 1.26 [1.19–1.33], P =6×10 − 16 ; pulse pressure OR, 1.31 [1.24–1.39], P =9×10 − 23 ). The effects of SBP, diastolic BP, and MAP were greater for coronary artery disease than PAD (SBP ratio of Ors, 1.06 [1.0–1.12], P = 0.04; MAP ratio of OR, 1.15 [1.06–1.26], P =8.6×10 − 4 ; diastolic BP ratio of OR, 1.21 [1.08–1.35], P =6.9×10 − 4 ). Considered jointly, both pulse pressure and MAP directly increased risk of PAD (pulse pressure OR, 1.26 [1.17–1.35], P =3×10 − 10 ; MAP OR, 1.14 [1.06–1.23], P =2×10 − 4 ). The effects of antihypertensive medications were estimated using genetic instruments. SBP-lowering via β-blocker (OR, 0.74 per 10 mm Hg decrease in SBP [95% CI, 0.65–0.84]; P =5×10 − 6 ), loop diuretic (OR, 0.66 [0.48–0.91], P =0.01), and thiazide diuretic (OR, 0.57 [0.41–0.79], P =6×10 − 4 ) associated variants were protective of PAD. Conclusions: Higher BP is likely to cause PAD. BP-lowering through β blockers, loop diuretics, and thiazide diuretics (as proxied by genetic variants) was associated with decreased risk of PAD. Future study is needed to clarify the specific mechanisms by which BP influences PAD.

Evaluation of genes associated with undescended testes as predictors of TGCT susceptibility.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1539-1539
Author(s):  
Ariela Marshall ◽  
Stephanie L. Ciosek ◽  
Saran Vardhanabhuti ◽  
Nandita Mitra ◽  
David J. Vaughn ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Association Studies ◽  
Snp Array ◽  
Genetic Risk Factors ◽  
Genome Wide Association Studies ◽  
Undescended Testes ◽  
Genome Wide ◽  
Increased Risk ◽  
Genotype Information

1539 Background: Testicular germ cell tumors (TGCTs) are highly heritable. Cryptorchidism (undescended testes; UDT) is a strong risk factor for TGCT, with increased risk to both the ipsilateral and contralateral testes. However, recent genome-wide association studies (GWAS) identifying genetic variants associated with TGCT susceptibility have not found differences in genotype carriage between TGCT patients with and without UDT. We investigated the role of potential risk variants for UDT as risk factors for TGCT. Methods: 1300 SNPs in and around 25 gene regions with published associations with UDT were evaluated in 474 TGCT cases (45 with UDT) and 919 controls. Genotype information was available from the Affymetrix Genome-Wide Human SNP Array 6.0. Statistical analysis was performed using PLINK, and statistical significance was assessed by Fisher's Exact test. Results: Comparing TGCT cases with and without UDT, variants in the region of four genes (EPHB2, ESR1, SEMA3C, TGFBR3) were suggestively associated with UDT. When TGCT cases with UDT were compared with unaffected controls, the associations all met the required level of significance (p < 4 x 10-5). Only variation at ESR1 approached significance (P=0.0004) when TGCT cases and unaffected controls were compared. Conclusions: We identified variants at three genetic loci - SEMA3C, TGFBR3 and EPHB2 - that were significantly associated with UDT, but not with TGCT. The association of variation in EPHB2 and SEMA3C with UDT are novel findings. While associated with UDT, variation at ESR1 is also potentially associated with TGCT risk. These data continue to suggest that genetic risk factors for UDT are largely independent of those for TGCT. Thus, screening for TGCT could be targeted in a UDT population to those with genetic risk factors. Further studies should be done to investigate the genetic link between UDT and TGCT.

scholarly journals Genetic determinants of glucose levels in pregnancy: genetic risk scores analysis and GWAS in the Norwegian STORK cohort

2018 ◽  
Vol 179 (6) ◽  
pp. 363-372 ◽  
Author(s):  
Gunn-Helen Moen ◽  
Marissa LeBlanc ◽  
Christine Sommer ◽  
Rashmi B Prasad ◽  
Tove Lekva ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Genetic Risk ◽  
Association Studies ◽  
Risk Scores ◽  
Oral Glucose ◽  
Genome Wide Association Studies ◽  
Shape Information ◽  
Genetic Risk Scores ◽  
Genome Wide ◽  
In Pregnancy

Objective Hyperglycaemia during pregnancy increases the risk of adverse health outcomes in mother and child, but the genetic aetiology is scarcely studied. Our aims were to (1) assess the overlapping genetic aetiology between the pregnant and non-pregnant population and (2) assess the importance of genome-wide polygenic contributions to glucose traits during pregnancy, by exploring whether genetic risk scores (GRSs) for fasting glucose (FG), 2-h glucose (2hG), type 2 diabetes (T2D) and BMI in non-pregnant individuals were associated with glucose measures in pregnant women. Methods We genotyped 529 Norwegian pregnant women and constructed GRS from known genome-wide significant variants and SNPs weakly associated (p > 5 × 10−8) with FG, 2hG, BMI and T2D from external genome-wide association studies (GWAS) and examined the association between these scores and glucose measures at gestational weeks 14–16 and 30–32. We also performed GWAS of FG, 2hG and shape information from the glucose curve during an oral glucose tolerance test (OGTT). Results GRSFG explained similar variance during pregnancy as in the non-pregnant population (~5%). GRSBMI and GRST2D explained up to 1.3% of the variation in the glucose traits in pregnancy. If we included variants more weakly associated with these traits, GRS2hG and GRST2D explained up to 2.4% of the variation in the glucose traits in pregnancy, highlighting the importance of polygenic contributions. Conclusions Our results suggest overlap in the genetic aetiology of FG in pregnant and non-pregnant individuals. This was less apparent with 2hG, suggesting potential differences in postprandial glucose metabolism inside and outside of pregnancy.

TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer

2018 ◽  
Vol 27 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Gintare Dargiene ◽  
Greta Streleckiene ◽  
Jurgita Skieceviciene ◽  
Marcis Leja ◽  
Alexander Link ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Atrophic Gastritis ◽  
Genetic Polymorphisms ◽  
Association Studies ◽  
Control Group ◽  
Similar Distribution ◽  
Genome Wide Association Studies ◽  
Increased Risk ◽  
Infection Susceptibility ◽  
H Pylori

Background & Aims: Previous genome-wide association studies showed that genetic polymorphisms in toll-like receptor 1 (TLR1) and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) genes were associated with gastric cancer (GC) or increased Helicobacter pylori (H. pylori) infection susceptibility. The aim of this study was to evaluate the association between TLR1 and PRKAA1 genes polymorphisms and H.pylori infection, atrophic gastritis (AG) or GC in the European population.Methods: Single-nucleotide polymorphisms (SNPs) were analysed in 511 controls, 340 AG patients and 327 GC patients. TLR1 C>T (rs4833095) and PRKAA1 C>T (rs13361707) were genotyped by the real-time polymerase chain reaction. H. pylori status was determined by testing for anti-H. pylori IgG antibodies in the serum.Results: The study included 697 (59.2%) H. pylori positive and 481 (40.8%) H. pylori negative cases. We observed similar distribution of TLR1 and PRKAA1 alleles and genotypes in H. pylori positive and negative cases. TLR1 and PRKAA1 SNPs were not linked with the risk of AG. TC genotype of TLR1 gene was more prevalent in GC patients compared to the control group (29.7% and 22.3% respectively, p=0.002). Carriers of TC genotype had a higher risk of GC (aOR=1.89, 95% CI: 1.26–2.83, p=0.002). A similar association was observed in a dominant inheritance model for TLR1 gene SNP, where comparison of CC+TC vs. TT genotypes showed an increased risk of GC (aOR=1.86, 95% CI: 1.26–2.75, p=0.002). No association between genetic polymorphism in PRKAA1 gene and GC was observed.Conclusions: TLR1 rs4833095 SNP was associated with an increased risk of GC in a European population, while PRKAA1 rs13361707 genetic variant was not linked with GC. Both genetic polymorphisms were not associated with H. pylori infection susceptibility or the risk of AG.

scholarly journals GWAS of serum ALT and AST reveals an association of SLC30A10 Thr95Ile with hypermanganesemia symptoms

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lucas D. Ward ◽  
Ho-Chou Tu ◽  
Chelsea B. Quenneville ◽  
Shira Tsour ◽  
Alexander O. Flynn-Carroll ◽  
...  
Keyword(s):  
Bile Duct ◽  
Extrahepatic Bile Duct ◽  
Association Studies ◽  
Missense Variant ◽  
Deficiency Anemia ◽  
Genome Wide Association Studies ◽  
Loss Of Function ◽  
Extrahepatic Bile Duct Cancer ◽  
Hepatocellular Damage ◽  
Increased Risk

AbstractUnderstanding mechanisms of hepatocellular damage may lead to new treatments for liver disease, and genome-wide association studies (GWAS) of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum activities have proven useful for investigating liver biology. Here we report 100 loci associating with both enzymes, using GWAS across 411,048 subjects in the UK Biobank. The rare missense variant SLC30A10 Thr95Ile (rs188273166) associates with the largest elevation of both enzymes, and this association replicates in the DiscovEHR study. SLC30A10 excretes manganese from the liver to the bile duct, and rare homozygous loss of function causes the syndrome hypermanganesemia with dystonia-1 (HMNDYT1) which involves cirrhosis. Consistent with hematological symptoms of hypermanganesemia, SLC30A10 Thr95Ile carriers have increased hematocrit and risk of iron deficiency anemia. Carriers also have increased risk of extrahepatic bile duct cancer. These results suggest that genetic variation in SLC30A10 adversely affects more individuals than patients with diagnosed HMNDYT1.

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