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The relationship between polymorphisms on chromosome 9p21 and age of onset of coronary heart disease in black and white women.

ABSTRACT: Genome-wide association studies have identified variants on chromosome 9p21 that are associated with coronary heart disease (CHD). The relationship between these variants and the age of onset of CHD is less clear. The aim of this study was to examine the allelic frequencies and haplotype structure of eight single-nucleotide polymorphisms (SNPs) on chromosome 9p21 in ethnically diverse women. We also explored the relationship between 9p21 SNPs and the age of CHD onset.There was considerable interethnic allelic and haplotype diversity across the 9p21 locus with only two SNPs (rs10757274 and rs4977574) in perfect linkage disequilibrium in both races, and only a small proportion of the haplotypes shared between the racial groups. With the exception of rs1333040, whites with at least one copy of the 9p21 SNP risk alleles were found to have CHD from 1.45 (rs10116277) to 4.77 (rs2383206) years earlier than those with the wild-type alleles. Blacks carrying at least one copy of the risk allele (92%) for rs1333040 had a CHD age of onset that was 6.5 years earlier than those with the wild-type alleles.Different variants on chromosome 9p21 may influence CHD age of onset in whites and blacks.

SUBMITTER: Beckie TM

PROVIDER: S-EPMC3101922 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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The relationship between polymorphisms on chromosome 9p21 and age of onset of coronary heart disease in black and white women.

Beckie Theresa M TM Groër Maureen W MW Beckstead Jason W JW

Genetic testing and molecular biomarkers 20110304 6

<h4>Aim</h4>Genome-wide association studies have identified variants on chromosome 9p21 that are associated with coronary heart disease (CHD). The relationship between these variants and the age of onset of CHD is less clear. The aim of this study was to examine the allelic frequencies and haplotype structure of eight single-nucleotide polymorphisms (SNPs) on chromosome 9p21 in ethnically diverse women. We also explored the relationship between 9p21 SNPs and the age of CHD onset.<h4>Results</h4> ...[more]

PMID: 21375403

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Project description:BackgroundGenetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.MethodsA variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.ResultsMeta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction <0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).ConclusionsIn contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.

Project description:BACKGROUND: We investigated whether 9p21 polymorphisms are associated with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function. METHODS: The participants of the MASS II were genotyped for 9p21 polymorphisms (rs10757274, rs2383206, rs10757278 and rs1333049). Survival curves were calculated with the Kaplan-Meier method and compared with the log-rank statistic. We assessed the relationship between baseline variables and the composite end-point of death, death from cardiac causes and myocardial infarction using a Cox proportional hazards survival model. RESULTS: We observed significant differences between patients within each polymorphism genotype group for baseline characteristics. The frequency of diabetes was lower in patients carrying GG genotype for rs10757274, rs2383206 and rs10757278 (29.4%, 32.8%, 32.0%) compared to patients carrying AA or AG genotypes (49.1% and 39.2%, p?=?0.01; 52.4% and 40.1%, p?=?0.01; 47.8% and 37.9%, p?=?0.04; respectively). Significant differences in genotype frequencies between double and triple vessel disease patients were observed for the rs10757274, rs10757278 and rs1333049. Finally, there was a higher incidence of overall mortality in patients with the GG genotype for rs2383206 compared to patients with AA and AG genotypes (19.5%, 11.9%, 11.0%, respectively; p?=?0.04). Moreover, the rs2383206 was still significantly associated with a 1.75-fold increased risk of overall mortality (p?=?0.02) even after adjustment of a Cox multivariate model for age, previous myocardial infarction, diabetes, smoking and type of coronary anatomy. CONCLUSIONS: Our data are in accordance to previous evidence that chromosome 9p21 genetic variation may constitute a genetic modulator in the cardiovascular system in different scenarios. In patients with established CAD, we observed an association between the rs2383206 and higher incidence of overall mortality and death from cardiac causes in patients with multi-vessel CAD.

Project description:Blacks have higher coronary heart disease (CHD) mortality compared with whites. However, a previous study suggests that nonfatal CHD risk may be lower for black versus white men.We compared fatal and nonfatal CHD incidence and CHD case-fatality among blacks and whites in the Atherosclerosis Risk in Communities study (ARIC), the Cardiovascular Health Study (CHS), and the Reasons for Geographic and Racial Differences in Stroke study (REGARDS) by sex. Participants 45 to 64 years of age in ARIC (men=6479, women=8488) and REGARDS (men=5296, women=7822), and ?65 years of age in CHS (men=1836, women=2790) and REGARDS (men=3381, women=4112), all without a history of CHD, were analyzed. Fatal and nonfatal CHD incidence was assessed from baseline (ARIC=1987-1989, CHS=1989-1990, REGARDS=2003-2007) through up to 11 years of follow-up.Age-adjusted hazard ratios comparing black versus white men 45 to 64 years of age in ARIC and REGARDS were 2.09 (95% confidence interval, 1.42-3.06) and 2.11 (1.32-3.38), respectively, for fatal CHD, and 0.82 (0.64-1.05) and 0.94 (0.69-1.28), respectively, for nonfatal CHD. After adjustment for social determinants of health and cardiovascular risk factors, hazard ratios in ARIC and REGARDS were 1.19 (95% confidence interval, 0.74-1.92) and 1.09 (0.62-1.93), respectively, for fatal CHD, and 0.64 (0.47-0.86) and 0.67 (0.48-0.95), respectively, for nonfatal CHD. Similar patterns were present among men ?65 years of age in CHS and REGARDS. Among women 45 to 64 years of age in ARIC and REGARDS, age-adjusted hazard ratios comparing blacks versus whites were 2.61 (95% confidence interval, 1.57-4.34) and 1.79 (1.06-3.03), respectively, for fatal CHD, and 1.47 (1.13-1.91) and 1.29 (0.91-1.83), respectively, for nonfatal CHD. After multivariable adjustment, hazard ratios in ARIC and REGARDS were 0.67 (95% confidence interval, 0.36-1.24) and 1.00 (0.54-1.85), respectively, for fatal CHD, and 0.70 (0.51-0.97) and 0.70 (0.46-1.06), respectively, for nonfatal CHD. Racial differences in CHD incidence were attenuated among older women. CHD case fatality was higher among black versus white men and women, and the difference remained similar after multivariable adjustment.After accounting for social determinants of health and risk factors, black men and women have similar risk for fatal CHD compared with white men and women, respectively. However, the risk for nonfatal CHD is consistently lower for black versus white men and women.

Project description:Excess urinary albumin excretion is more common in black than white individuals and is more strongly associated with incident stroke risk in black vs white individuals. Whether similar associations extend to coronary heart disease (CHD) is unclear.To determine whether the association of urinary albumin excretion with CHD events differs by race.Prospective cohort study of black and white US adults aged 45 years and older who were enrolled within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study between 2003 and 2007 with follow-up through December 31, 2009. We examined race-stratified associations of urinary albumin-to-creatinine ratio (ACR) in 2 groups: (1) incident CHD among 23,273 participants free of CHD at baseline; and (2) first recurrent CHD event among 4934 participants with CHD at baseline.Expert-adjudicated incident and recurrent myocardial infarction and acute CHD death.A total of 616 incident CHD events (421 nonfatal MIs and 195 CHD deaths) and 468 recurrent CHD events (279 nonfatal MIs and 189 CHD deaths) were observed over a mean time of 4.4 years of follow-up. Among those free of CHD at baseline, age- and sex-adjusted incidence rates of CHD per 1000 person-years of follow-up increased with increasing categories of ACR in black and white participants, with rates being nearly 1.5-fold greater in the highest category of ACR (>300 mg/g) in black participants (20.59; 95% CI, 14.36-29.51) vs white participants (13.60; 95% CI, 7.60-24.25). In proportional hazards models adjusted for traditional cardiovascular risk factors and medications, higher baseline urinary ACR was associated with greater risk of incident CHD among black participants (hazard ratio [HR] comparing ACR >300 vs <10 mg/g, 3.21 [95% CI, 2.02-5.09]) but not white participants (HR comparing ACR >300 vs <10 mg/g, 1.49 [95% CI, 0.80-2.76]) (P value for interaction?=?.03). Among those with CHD at baseline, fully adjusted associations of baseline urinary ACR with first recurrent CHD event were similar between black participants (HR comparing ACR >300 vs <10 mg/g, 2.21 [95% CI, 1.22-4.00]) vs white participants (HR comparing ACR >300 vs <10 mg/g, 2.48 [95% CI, 1.61-3.78]) (P value for interaction?=?.53).Higher urinary ACR was associated with greater risk of incident but not recurrent CHD in black individuals when compared with white individuals. These data confirm that black individuals appear more susceptible to vascular injury.

Dataset Information

The relationship between polymorphisms on chromosome 9p21 and age of onset of coronary heart disease in black and white women.

Publications

The relationship between polymorphisms on chromosome 9p21 and age of onset of coronary heart disease in black and white women.

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