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Molecular Relationships between Bronchial Asthma and Hypertension as Comorbid Diseases.

ABSTRACT: Comorbidity, a co-incidence of several disorders in an individual, is a common phenomenon. Their development is governed by multiple factors, including genetic variation. The current study was set up to look at associations between isolated and comorbid diseases of bronchial asthma and hypertension, on one hand, and single nucleotide polymorphisms associated with regulation of gene expression (eQTL), on the other hand. A total of 96 eQTL SNPs were genotyped in 587 Russian individuals. Bronchial asthma alone was found to be associated with rs1927914 (TLR4), rs1928298 (intergenic variant), and rs1980616 (SERPINA1); hypertension alone was found to be associated with rs11065987 (intergenic variant); rs2284033 (IL2RB), rs11191582 (NT5C2), and rs11669386 (CARD8); comorbidity between asthma and hypertension was found to be associated with rs1010461 (ANG/RNASE4), rs7038716, rs7026297 (LOC105376244), rs7025144 (intergenic variant), and rs2022318 (intergenic variant). The results suggest that genetic background of comorbidity of asthma and hypertension is different from genetic backgrounds of both diseases manifesting isolated.

SUBMITTER: Bragina EY

PROVIDER: S-EPMC6348747 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Molecular Relationships between Bronchial Asthma and Hypertension as Comorbid Diseases.

Bragina Elena Yu EY Goncharova Irina A IA Garaeva Anna F AF Nemerov Evgeniy V EV Babovskaya Anastasija A AA Karpov Andrey B AB Semenova Yulia V YV Zhalsanova Irina Z IZ Gomboeva Densema E DE Saik Olga V OV Zolotareva Olga I OI Ivanisenko Vladimir A VA Dosenko Victor E VE Hofestaedt Ralf R Freidin Maxim B MB

Journal of integrative bioinformatics 20181210 4

Comorbidity, a co-incidence of several disorders in an individual, is a common phenomenon. Their development is governed by multiple factors, including genetic variation. The current study was set up to look at associations between isolated and comorbid diseases of bronchial asthma and hypertension, on one hand, and single nucleotide polymorphisms associated with regulation of gene expression (eQTL), on the other hand. A total of 96 eQTL SNPs were genotyped in 587 Russian individuals. Bronchial ...[more]

PMID: 30530896

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Project description:Linkage disequilibrium (LD) of single nucleotide polymorphisms (SNPs) of TLR4/AL160272.2 (rs1927914, rs1928298, rs7038716, rs7026297, rs7025144) was estimated in the Slavs of West Siberia. We further investigated an association of SNPs in TLR4/AL160272.2 (rs1927914, rs7038716, rs7025144), SERPINA1 (rs1980616), ATXN2/BRAP (rs11065987), IL2RB (rs2284033), NT5C2 (rs11191582), CARD8 (rs11669386), ANG/RNASE4 (rs1010461), and ABTB2/ САТ (rs2022318) genes with bronchial asthma (BA), arterial hypertension (AH) and their comorbidity. Then, the disease-associated SNPs were annotated in silico in relation to their potential regulatory functions. Strong LD was detected between rs1928298 and rs1927914, as well as rs7026297 and rs7038716 in the Slavs of West Siberia. It was found that the rs1927914 G allele of the TLR4 gene and the rs1980616 C allele of the SERPINA1 gene are associated with the predisposition to BA. These SNPs can affect binding affinity of transcription factors of the Pou and Klf4 families, as well as the expression levels of the TLR4 and SERPINA1 genes. The rs11065987 allele A of the ATXN2/BRAP genes, the rs11669386 A allele of the CARD8 gene, the rs2284033 allele G of the IL2RB gene, and the rs11191582 allele G of the NT5C2 gene were associated with the risk of AH. These variants can alter binding affinity of the Hoxa9, Irf, RORalpha1 and HMG-IY transcription factors, as well as the expression levels of the ALDH2, CARD8, NT5C2, ARL3, and SFXN2 genes in blood cells/vessels/heart, respectively. The risk of developing a comorbid phenotype of AD and AH is associated with the A allele of rs7038716 and the T allele of rs7025144 of the TLR4/AL160272.2 genes, the A allele of rs1010461 of the ANG gene and the C allele of rs2022318 of the ABTB2/CAT genes. Variants rs7038716 and rs7025144 can change the expression levels of the TLR4 gene in blood cells, while rs1010461 and rs2022318 influence the expression levels of the ANG and RNASE4 genes as well as the CAT and ABTB2 genes in blood cells, lungs/vessels/heart.

Project description:Background: Uncontrolled asthma (BA) can be complicated by cardiac conduction disturbances and arrhythmias. It is typical mainly for adult asthmatics patients. In asthmatics children the effect of bronchoconstriction on cardiac conduction, including the supraventricular component of the ECG, is currently under discussion. The objective of the research is to analyze ECG parameters of the atrial complex and atrioventricular conduction and to assess their relationship with spirometric indicators in children with BA. Methods: Hundred three patients with BA from the age of 6–17 years were examined. The spirometric parameters were evaluated, including the Tiffeneau index (TI): FEV1/FVC (%), according to the level of which the patient groups were distinguished. Group 1 (G1): with TI more than 85%, (n = 15); Group 2 (G2): with TI from 85 to 75%, (n = 40); Group 3 (G3): with TI <75%, (n = 48). The ECG parameters that characterize supraventricular conduction, including the PQ interval (sec) and the sPQ segment (sec), were analyzed. We had calculated relative PQ (rPQ) by the formula rPQ=PQ/PQmed, where PQ is the patient's PQ, PQmed are the median PQ values of healthy children of age selected. Results: The duration of the PQ in groups G1 and G2 was 0.13 (0.11; 0.14) s; and 0.13 (0.12; 0.14) s, respectively, which is statistically significantly less than in patients of groups G3–0.14 (0.13; 0.15] s, p = 0.01. The duration of the sPQ segment in children of groups G1 and G2 was also generally shorter than in patients of groups G3, and amounted, respectively, to 0.05 (0.04; 0.06) s, 0.04 (0.04; 0.05) s, and 0.06 (0.04; 0.07) s, p = 0.02. The rPQ increased progressively as TI decreased and amounted in G1 to 92.9 (85.7; 106.3) %, in G2 100.0 (92.9; 103.0) %, and in G3 104 (100.0; 107.7) %, p = 0.009. A statistically significant negative correlation between IT and PQ–r = ?0.23, p = 0.02; with sPQ–r = ?0.20, p = 0.045; and with rPQ–r = ?0.25, p = 0.01 was revealed. Conclusion: A decrease in TI in asthmatics children is associated with a prolongation of the PQ. This may indicate a slowdown in supraventricular conduction in patients with uncontrolled asthma and, thus, be considered as a risk for the formation of subsequent supraventricular arrhythmias.

Project description:IntroductionThe rise in Gastro-Esophageal Reflux Disease (GERD) prevalence appears to have coincided with a simultaneous increase in the prevalence of diabetes mellitus, hypertension and bronchial asthma amongst the Indian population. Despite being evaluated extensively for their role as a risk factor for GERD, till date this relationship has remained a debatable one. Moreover, literature available on such studies conducted within Indian population remains scarce.AimThe aim of the present study was to examine the risk of developing GERD in patients suffering from diabetes mellitus, hypertension and asthma in a Southern Indian population. The present retrospective, triple cohort and hospital based study was conducted by accessing the patient records from the medical records department of a tertiary care hospital in Southern India.Materials and MethodsThe patient’s records were accessed from the year 2011 onwards. Relative Risk (RR) was calculated to determine the risk of development of GERD with every disease. Chi-square test was used to determine the statistical significance of the relationship between each disease and the development of GERD. A p-value of <0.05 was considered statistically significant.ResultsIn view of the time constraints as well as the limitations of the inclusion and exclusion criteria, data pertaining to only 40, 71 and 53 patients in Cohort 1 (diabetics), 2 (hypertensives) and 3 (bronchial asthmatics) respectively could be analyzed in the present study. The relative risk of GERD development was greater than 1 for patients belonging to Cohort 2 and 3, suggesting that the risk of GERD development is higher amongst hypertensives and asthmatics. Surprisingly, the diabetics (Cohort 1) were not associated with a high risk of GERD development. However, the relationship between any of the disease and GERD development was not statistically significant.ConclusionThe present study found an increased risk of GERD development amongst patients suffering from hypertension and bronchial asthma, but not with diabetes mellitus.

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Molecular Relationships between Bronchial Asthma and Hypertension as Comorbid Diseases.

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Molecular Relationships between Bronchial Asthma and Hypertension as Comorbid Diseases.

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