Dataset Information

Association of Zinc Finger, C3HC-Type Containing 1 (ZC3HC1) rs11556924 Genetic Variant With Hypertension in a Finnish Population, the TAMRISK Study.

ABSTRACT: In a recent genome-wide association study, the zinc finger, C3HC-type containing 1 (ZC3HC1) polymorphism was strongly associated with coronary artery disease (CAD) by an unknown mechanism. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is related with CAD through low-density lipoprotein (LDL) metabolism. The association of both of the above genetic variants with hypertension was studied in a Finnish 50-year-old cohort.A total of 325 hypertensive cases and 444 nonhypertensive controls were obtained from the Tampere adult population cardiovascular risk study. Samples were genotyped for ZC3HC1 rs11556924 and PCSK9 rs11206510 polymorphisms using Competitive Allele Specific PCR technique. A subpopulation that had available follow-up data from ages of 40, 45, and 50 years was also analyzed.ZC3HC1 rs11556924 (C?>?T) genotype CC was associated with hypertension compared with the T-allele carriers (P?=?0.013). PCSK9 rs11206510 (T?>?C) genotype was not associated with hypertension. Its major TT-genotype was associated with higher total cholesterol (P?=?0.044) and LDL (P?=?0.029) compared with the C-allele.We report for the first time that ZC3HC1 rs11556924 was associated with essential hypertension in 50-year-old patients. Although PCSK9 rs11206510 was not associated with hypertension, our study confirms its association with serum cholesterol levels.

SUBMITTER: Kunnas T

PROVIDER: S-EPMC4616712 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Zinc Finger, C3HC-Type Containing 1 (ZC3HC1) rs11556924 Genetic Variant With Hypertension in a Finnish Population, the TAMRISK Study.

Kunnas Tarja T Nikkari Seppo T ST

Medicine 20150801 32

In a recent genome-wide association study, the zinc finger, C3HC-type containing 1 (ZC3HC1) polymorphism was strongly associated with coronary artery disease (CAD) by an unknown mechanism. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is related with CAD through low-density lipoprotein (LDL) metabolism. The association of both of the above genetic variants with hypertension was studied in a Finnish 50-year-old cohort.A total of 325 hypertensive cases and 444 nonhypertensive controls were ...[more]

PMID: 26266351

Similar Datasets

Project description:Increased inducible nitric oxide synthase (iNOS) activity and expression has been associated with hypertension, but less is known whether the 2 known functional polymorphic sites in the iNOS gene (g.-1026 C/A (rs2779249), g.2087 G/A (rs2297518)) affect susceptibility to hypertension. The objective of this study was to investigate the association between the genetic variants of iNOS and diagnosed hypertension in a Finnish cohort.This study included 320 hypertensive cases and 439 healthy controls. All participants were 50-year-old men and women and the data were collected from the Tampere adult population cardiovascular risk study (TAMRISK). DNA was extracted from buccal swabs and iNOS single nucleotide polymorphisms (SNPs) were analyzed using KASP genotyping PCR. Data analysis was done by logistic regression.At the age of 50 years, the SNP rs2779249 (C/A) associated significantly with hypertension (P?=?0.009); specifically, subjects carrying the A-allele had higher risk of hypertension compared to those carrying the CC genotype (OR?=?1.47; CI?=?1.08-2.01; P?=?0.015). In addition, a 15-year follow-up period (35, 40, and 45 years) of the same individuals showed that carriers of the A-allele had more often hypertension in all of the studied age-groups. The highest risk for developing hypertension was obtained among 35-year-old subjects (odds ratio [OR] 3.83; confidence interval [CI]?=?1.20-12.27; P?=?0.024). Those carrying variant A had also significantly higher readings of both systolic (P?=?0.047) and diastolic (P?=?0.048) blood pressure during the follow-up. No significant associations between rs2297518 (G/A) variants alone and hypertension were found. However, haplotype analysis of rs2779249 and rs2297518 revealed that individuals having haplotype H3 which combines both A alleles (CA-GA, 19.7% of individuals) was more commonly found in the hypertensive group than in the normotensive group (OR?=?2.01; CI?=?1.29-3.12; P?=?0.002).In conclusion, there was a significant association between iNOS genetic variant (rs2779249) and hypertension in the genetically homogenous Finnish population. Those who carried the rare A-allele of the gene had higher risk for hypertension already at the age of 35 years.

Project description:ImportanceThe c.1102C>T, p.(Gln368Ter) variant in the myocilin (MYOC) gene is a known risk allele for glaucoma. It is the most common MYOC risk variant for glaucoma among individuals of European ancestry, and its prevalence is highest in Finland. Furthermore, exfoliation syndrome has high prevalence in Scandinavia, making the Finnish population ideal to study the association of the variant with different types of glaucoma.ObjectivesTo examine the association and penetrance of MYOC p.(Gln368Ter) (rs74315329) variant with different types of glaucoma in a Finnish population.Design, setting, and participantsThis genetic association study included individuals of Finnish ancestry in the FinnGen project. The participants were collected from Finnish biobanks, and the disease end points were defined using nationwide registries. The MYOC c.1102C>T variant was either directly genotyped or imputed with microarrays. Recruitment of samples to FinnGen was initiated in 2017, and data analysis was performed between December 2019 and May 2020.Main outcomes and measuresThe main outcomes were odds ratios (ORs) and penetrance with different types of glaucoma and in different age groups.ResultsA total of 218 792 individuals were included in this study (mean [SD] age 52.4 [17.5] years; 123 579 women [56.5%]), including 8591 (3.9%) with glaucoma, 3412 (1.6%) with primary open-angle glaucoma, 1515 (0.7%) with exfoliation glaucoma, 892 (0.4%) with normal-tension glaucoma, and 4766 (2.2%) with suspected glaucoma. The minor allele frequency of MYOC p.(Gln368Ter) was 0.28%. Individuals with the heterozygous variant had higher odds of primary open-angle glaucoma (OR, 3.36; 95% CI, 2.55-4.37), overall glaucoma (OR, 2.58; 95% CI, 2.12-3.13), suspected glaucoma (OR, 2.53; 95% CI, 1.93-3.26), exfoliation glaucoma (OR, 2.61; 95% CI, 1.60-4.02), and undergoing glaucoma-related operations (OR, 5.45; 95% CI, 2.95-9.28). The penetrance of heterozygous MYOC p.(Gln368Ter) was 5.2% in individuals with primary open-angle glaucoma, 9.6% in individuals with glaucoma, 5.4% in individuals with suspected glaucoma, and 1.9% in individuals with exfoliation glaucoma. There was no significant association with normal-tension glaucoma (OR, 1.69; 95% CI, 0.72-3.35).Conclusions and relevanceThis genetic association study found that the MYOC p.(Gln368Ter) variant was associated with exfoliation glaucoma. The association with normal-tension glaucoma could not be replicated. These findings suggest that MYOC p.(Gln368Ter) was associated with open-angle glaucoma and exfoliation glaucoma in a Finnish population.

Dataset Information

Association of Zinc Finger, C3HC-Type Containing 1 (ZC3HC1) rs11556924 Genetic Variant With Hypertension in a Finnish Population, the TAMRISK Study.

Publications

Association of Zinc Finger, C3HC-Type Containing 1 (ZC3HC1) rs11556924 Genetic Variant With Hypertension in a Finnish Population, the TAMRISK Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets