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Association between ATP2B1 and CACNB2 polymorphisms and high blood pressure in a population of Lithuanian children and adolescents: a cross-sectional study.

ABSTRACT: OBJECTIVES:Recently, genome-wide associated studies have identified several genetic loci that are associated with elevated blood pressure and could play a critical role in intracellular calcium homeostasis. The aim of this study was to assess the associations of ATP2B1 rs2681472 and CACNB2 rs12258967 gene polymorphisms with high blood pressure (HBP) among Lithuanian children and adolescents aged 12-15 years. STUDY DESIGN AND PARTICIPANTS:This was a cross-sectional study of a randomly selected sample of 646 12-15-year-old adolescents who participated in the survey 'The Prevalence and Risk Factors of HBP in 12-15?Year-Old Lithuanian Children and Adolescents (from November 2010 to April 2012)'. Anthropometric parameters and BP were measured. The participants with HBP were screened on two separate occasions. Subjects were genotyped ATP2B1 rs2681472 and CACNB2 rs12258967 gene polymorphisms using real-time PCR method. RESULTS:The prevalence of HBP was 36.7%, significantly higher for boys than for girls. In the multivariate analysis, after adjustment for body mass index and waist circumference, boys with CACNB2 CG genotype, CACNB2 GG genotype and CACNB2 CG +GG?genotype had higher odds of having HBP in codominant (adjusted OR (aOR)=1.92; 95%?CI 1.16 to 3.18, p=0.011; and aOR=2.64; 95%?CI 1.19 to 5.90, p=0.018) and in dominant (aOR=2.05; 95%?CI 1.27 to 3.30, p=0.003) inheritance models. Girls carrying CACNB2 CG genotype and CACNB2 CG +GG?genotype had increased odds of HBP in codominant (aOR=1.82; 95%?CI 1.02 to 3.24, p=0.044) and in dominant (aOR=1.89; 95%?CI 1.09 to 3.28, p=0.023) inheritance models. Furthermore, significant associations were found in additive models separately for boys (aOR=1.72; 95%?CI 1.20 to 2.46, p=0.003) and girls (aOR=1.52; 95%?CI 1.05 to 2.20, p=0.027). No significant association was found between ATP2B1 gene polymorphism and the odds of HBP. CONCLUSIONS:Our results indicate that CACNB2 gene polymorphism was significantly associated with higher odds of HBP in Lithuanian adolescents aged 12-15 years.

SUBMITTER: Simonyte S

PROVIDER: S-EPMC6042568 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Association between <i>ATP2B1</i> and <i>CACNB2</i> polymorphisms and high blood pressure in a population of Lithuanian children and adolescents: a cross-sectional study.

Simonyte Sandrita S Kuciene Renata R Dulskiene Virginija V Lesauskaite Vaiva V

BMJ open 20180707 7

<h4>Objectives</h4>Recently, genome-wide associated studies have identified several genetic loci that are associated with elevated blood pressure and could play a critical role in intracellular calcium homeostasis. The aim of this study was to assess the associations of <i>ATP2B1</i> rs2681472 and <i>CACNB2</i> rs12258967 gene polymorphisms with high blood pressure (HBP) among Lithuanian children and adolescents aged 12-15 years.<h4>Study design and participants</h4>This was a cross-sectional st ...[more]

PMID: 29982197

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Project description:Epidemiological studies have demonstrated the influence of environmental factors on HBP in the population of Lithuanian children, although the role of genetic factors in hypertension has not yet been studied. The aim of this study was to assess the distribution of AGTR1, AGT, and ACE genotypes in the Lithuanian child population and to determine whether these genotypes have an impact on HBP in childhood.This cross-sectional study enrolled 709 participants aged 12-15 years. The subjects were genotyped for AGT (M235 T, rs699), AGTR1 (A1166C, rs5186), and ACE (rs4340) gene polymorphisms using real-time and conventional polymerase chain reactions. Blood pressure and anthropometric parameters were measured.The prevalence of HBP was 38.6% and was more frequently detected in boys than in girls (47.9% vs. 29.5%; p < 0.001). No significant differences in the frequencies of the AGT or AGTR1 genotypes or alleles between boys and girls were observed, except for ACE genotypes. The mean SBP value was higher in HBP subjects with ACE ID genotype compared to those with ACE II homozygotes (p = 0.04). No significant differences in BP between different AGT and AGTR1 genotype groups were found. Boys who carried the ACE ID + DD genotypes had higher odds of having HBP than carriers of the ACE II genotype did (controlling for the body mass index (BMI): ORMH = 1.83; 95% CI, 1.11-3.02, p = 0.024; and controlling for waist circumference (WC): ORMH = 1.76; 95% CI, 1.07-2.92, p = 0.035). These associations were not significant among girls. The same trend was observed in the multivariate analysis - after adjustment for BMI and WC, only boys with ACE ID genotype and ACE ID + DD genotypes had statistically significantly increased odds of HBP (aOR = 2.05; 95% CI, 1.19-3.53 (p = 0.01) and aOR = 1.82; 95% CI, 1.09-3.04 (p = 0.022), respectively).The evaluated polymorphisms of the AGT and AGTR1 genes did not contribute to the presence of HBP in the present study and may be seen as predisposing factors, while ACE ID genotypes were associated with significantly increased odds for the development of HBP in the Lithuanian child and adolescent population - especially in boys.

Project description:ObjectiveWe sought to explore various correlates of blood pressure (BP) and hypertension, and to identify the most important aggregate combination of correlates for BP in South Asian children.DesignCross-sectional study SETTING: Community-based recruitment in two Canadian cities PARTICIPANTS: South Asian children (n=762) provided a range of physiological, lifestyle and social variables. BP was assessed using an automated device. Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) and BP were transformed to z-scores using published standards.Outcome measuresLinear and logistic regression analyses were used to explore associations between the range of variables with BP z-scores and hypertension while stepwise regression was used to identify aggregate factors that provided explanatory capacity for systolic BP (SBP) and diastolic BP (DBP) z-scores.ResultsA range of variables were associated with BP z-score and hypertension in unadjusted analysis. On adjustment for confounders, the association between age (?=-0.054, 95%?CI=-0.078 to 0.029), female sex (?=-0.208, 95% CI=-0.350 to -0.067), height (?=0.022, 95% CI=0.011 to 0.033), weight (?=0.047, 95% CI=0.040 to 0.055), BMI z-score (?=0.292, 95%?CI=0.249 to 0.336), WC z-score (?=0.273, 95% CI=0.219 to 0.326), WHtR z-score (?=0.289, 95% CI=0.236 to 0.342), heart rate (?=0.016, 95% CI=0.010 to 0.022), child's perception of body image (?=0.183, 95% CI=0.128 to 0.239) and grip strength (?=0.025, 95% CI=0.007 to 0.043) with SBP z-score remained. In stepwise regression, age, sex, BMI z-score, heart rate and weight accounted for 30% of the variance of SBP z-score, while age, BMI z-score, heart rate and daily fast food intake accounted for 23% of the DBP z-score variance.ConclusionOur findings suggest that variables, such as age, sex, height, adiposity and heart rate, provide stronger explanatory capacity to BP variance and hypertension risk than other variables in South Asian children.

Project description:ObjectiveThe present study aimed to conduct a systematic review and meta-analysis to evaluate the relationships between ATP2B1 gene polymorphisms with blood pressure (BP) level and susceptibility to hypertension.MethodsPubMed, Web of Science, Embase and China National Knowledge Infrastructure (CNKI) Databases were systematically searched by 2 independent researchers to screen studies on ATP2B1 gene polymorphisms and BP related phenotypes. The records retrieval period was limited from the formation of the database to March 4, 2021. Pooled odds rations (ORs) or β and their 95% confidence intervals (95%CI) were calculated to assess the association between ATP2B1 gene polymorphisms and the risk of hypertension or BP levels. Publication bias and sensitivity analysis were conducted to find potential bias. All the statistical analysis were conducted with Stata version 11.0 software.ResultsA total of 15 articles were ultimately included in the present study, including 15 polymorphisms of ATP2B1 gene. Nine articles (N = 65,362) reported the polymorphism rs17249754, and 7 articles(N = 91,997) reported rs2681472 (both loci were reported in 1 article). Meta-analysis showed that rs17249754 (G/A) and rs2681472 (A/G) were associated with the susceptibility to hypertension (rs17249754: OR = 1.19, 95%CI: 1.10-1.28; rs2681472: OR = 1.15, 95%CI: 1.12-1.17), and were positively associated with systolic BP (SBP) and diastolic blood pressure (DBP) (rs17249754: SBP, β=1.01, 95%CI: 0.86-1.16, DBP, β=0.48, 95%CI: 0.30-0.66; rs2681472: SBP, β=0.92, 95%CI: 0.77-1.07, DBP, β=0.50, 95%CI: 0.42-0.58) in the additive genetic model. Subgroup analysis stratified by race, population, sample size, and BP measurement method revealed that the association between A allele in rs2681472 polymorphism and risk of hypertension was slightly stronger in European (EUR) populations (OR = 1.16, 95%CI: 1.13-1.20) than in East Asians (OR = 1.14, 95%CI: 1.10-1.17). While in East Asians, relation between rs17249754 with risk of hypertension (OR = 1.19, 95%CI: 1.10-1.28) is stronger than rs2681472 (OR = 1.14, 95%CI: 1.10-1.17).ConclusionsOur study demonstrated that ATP2B1 gene polymorphism rs2681472 and rs17249754 were associated with BP levels and the susceptibility to hypertension.

Project description:Data on prevalence and characteristics of different high blood pressure subtypes are lacking among Chinese children. Regarding the mechanistic differences between isolated systolic high blood pressure and isolated diastolic high blood pressure and their different impact on end organ diseases, it is necessary to examine the prevalence of different high blood pressure subtypes in Chinese children and explore their associations with adiposity.Data were derived from the baseline data of a multi-centered cluster randomized controlled trial involving participants from China. High blood pressure was defined according to age-, gender- and height-specific 95th percentile developed by the National High Blood Pressure Education Program Working Group. Body mass index was used to classify underweight, normal weight, overweight and obesity.The prevalence of HBP was 10.2% and 8.9% for boys and girls, respectively. Isolated systolic high blood pressure is the dominant high blood pressure subtype among Chinese boys aged 6-17 years and girls aged 12-17 years, while isolated diastolic high blood pressure was the most common high blood pressure subtype in girls aged 6-11 years. In boys, the status of overweight doubled the risk of isolated systolic high blood pressure (95% CI, 1.73, 2.31; P < 0.001) compared with the normal weight group, and the risk for obese children was 4.32 (95% CI, 3.81, 4.90; P < 0.001). The corresponding odds ratios in girls were 2.04 (95% CI, 1.68, 2.48, P < 0.001) for overweight, and 4.0 (95% CI, 3.36, 4.76, P < 0.001) for obesity. Similar patterns were also observed in the association between combined systolic and diastolic high blood pressure and adiposity.The distribution of high blood pressure subtypes in boys differed from those in girls, and boys with adiposity showed a higher risk of high blood pressure than their female counterpart. Difference in strength of association between isolated diastolic high blood pressure and isolated systolic high blood pressure with body mass index was also found. These results may aid current strategies for preventing and controlling pediatric hypertension.

Dataset Information

Association between ATP2B1 and CACNB2 polymorphisms and high blood pressure in a population of Lithuanian children and adolescents: a cross-sectional study.

Publications

Association between <i>ATP2B1</i> and <i>CACNB2</i> polymorphisms and high blood pressure in a population of Lithuanian children and adolescents: a cross-sectional study.

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