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Contribution of syndecan-4 genetic variants to hypertension, the TAMRISK study.

ABSTRACT: BACKGROUND: A human syndecan-4 genetic variant (rs1981429) has previously been associated with lean tissue mass and intra-abdominal fat, and SNP rs4599 with resting energy expenditure in healthy early pubertal children. These variations could thus cause overweight and hypothetically lead to hypertension. Their association with body mass index and blood pressure was therefore studied in a Finnish cohort of adults. METHODS: The data was collected from the Tampere adult population cardiovascular risk study (TAMRISK). A total of 279 cases with hypertension and/or coronary artery disease (CAD), and 488 non-hypertensive healthy controls were selected from a Finnish periodic health examination 50-year-old cohort. Information was available also from their 45-year examination. DNA was extracted from buccal swabs and human syndecan-4 gene SNPs were analyzed using KASP genotyping. RESULTS: The SNP rs1981429 variant TT was significantly associated with hypertension, as compared to variants TG and GG at the age of 50 years (p=0.015). The variant TT was also associated with increased BMI at the ages of 45 and 50 years (p=0.008 and p=0.026, respectively). In addition, TT genotype associated with increased CAD prevalence (P=0.013). No significant associations between rs4599 variants and hypertension or BMI were found. In haplotype analysis the number of alleles T (rs1981429)/C (rs4599) was linearly associated with CAD prevalence; the highest prevalence (13%) was in haplotype TT/CC and lowest prevalence (1%) in haplotype GG/TT (p=0.01). CONCLUSION: Syndecan-4 polymorphisms were associated with essential hypertension, BMI, and CAD prevalence in the TAMRISK study.

SUBMITTER: Kunnas T

PROVIDER: S-EPMC4247658 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Contribution of syndecan-4 genetic variants to hypertension, the TAMRISK study.

Kunnas Tarja T Nikkari Seppo T ST

BMC research notes 20141119

<h4>Background</h4>A human syndecan-4 genetic variant (rs1981429) has previously been associated with lean tissue mass and intra-abdominal fat, and SNP rs4599 with resting energy expenditure in healthy early pubertal children. These variations could thus cause overweight and hypothetically lead to hypertension. Their association with body mass index and blood pressure was therefore studied in a Finnish cohort of adults.<h4>Methods</h4>The data was collected from the Tampere adult population card ...[more]

PMID: 25410619

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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:We previously identified 9 genes and chromosomal region 3q28 as susceptibility loci for Japanese patients with myocardial infarction, ischemic stroke, or chronic kidney disease by genome-wide or candidate gene association studies. In the present study, we investigated the possible association of 13 single nucleotide polymorphisms (SNPs) at these 10 loci with the prevalence of hypertension or their association with blood pressure (BP) in community-dwelling individuals in Japan. The study subjects comprised 6,027 individuals (2,250 subjects with essential hypertension, 3,777 controls) who were recruited into the Inabe Health and Longevity Study, a longitudinal genetic epidemiological study on atherosclerotic, cardiovascular and metabolic diseases. The subjects were recruited from individuals who visited the Health Care Center of Inabe General Hospital for an annual health checkup, and they are followed up each year (mean follow?up period, 5 years). Longitudinal analysis with a generalized estimating equation and with adjustment for age, gender, body mass index and smoking status revealed that rs2116519 of family with sequence similarity 78, member B (FAM78B; P=0.0266), rs6929846 of butyrophilin, subfamily 2, member A1 (BTN2A1; P=0.0013), rs146021107 of pancreatic and duodenal homeobox 1 (PDX1; P=0.0031) and rs1671021 of lethal giant larvae homolog 2 (Drosophila) (LLGL2; P=0.0372) were significantly (P<0.05) associated with the prevalence of hypertension. Longitudinal analysis with a generalized linear mixed-effect model and with adjustment for age, gender, body mass index and smoking status among individuals not taking anti-hypertensive medication revealed that rs6929846 of BTN2A1 was significantly associated with systolic (P=0.0017), diastolic (P=0.0008) and mean (P=0.0005) BP, and that rs2116519 of FAM78B, rs146021107 of PDX1 and rs1671021 of LLGL2 were significantly associated with diastolic (P=0.0495), systolic (P=0.0132), and both diastolic (P=0.0468) and mean (0.0471) BP, respectively. BTN2A1 may thus be a susceptibility gene for hypertension.

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Contribution of syndecan-4 genetic variants to hypertension, the TAMRISK study.

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Contribution of syndecan-4 genetic variants to hypertension, the TAMRISK study.

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