Chromosome 9p21.3 is Associated with Early-Onset Coronary Heart Disease in the Irish Population

Wang, Meng; Hughes, Anne E.; Patterson, Chris; Belton, Christine; Kee, Frank; McKeown, Pascal

doi:10.1155/2008/375617

Cited by 17 publications

(13 citation statements)

References 19 publications

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“…Similar findings were seen in the Irish population (Meng et al, 2008) where three SNPs at the 9p21 locus, which included the rs1333039 (P = 3·08 × 10 −7 ) were strongly associated with early onset CAD. The rs1333049 polymorphism was also associated with an earlier age of disease onset in two coronary disease cohorts (Ellis et al, 2010).…”

Section: Discussionsupporting

confidence: 78%

“…Several genome wide association studies (GWAS; Helgadottir et al, 2007;McPherson et al, 2007;Samani et al, 2007) and meta-analysis (Palomaki et al, 2010;Preuss et al, 2010) have implicated this region with increased risk of CAD, MI as well as progression of disease. Replication studies with different SNPs in this region in diverse populations including Irish (Meng et al, 2008), Japanese (Hinohara et al, 2008;Hiura et al, 2008), Koreans (Hinohara et al, 2008), Indians (AshokKumar et al, 2011;Bhanushali et al, 2011), Chinese (Ding et al, 2009), etc. have corroborated these findings.…”

Section: Introductionmentioning

confidence: 99%

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Variant at 9p21 rs1333049 is associated with age of onset of coronary artery disease in a Western Indian population: a case control association study

Bhanushali¹,

Contractor²,

Das³

2013

Genet. Res.

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The 9p21 chromosomal region has been associated with coronary artery disease (CAD) in many genome wide association studies (GWAS). To date no information exists regarding the rs1333039 SNP which showed the strongest association in the WTCCC GWAS with CAD risk in the Indian population. The present study attempts to replicate the findings in the Indian population. Genotyping for rs1333049 was done in 229 cases and 151 controls by allele-specific real-time assay. A higher frequency of the risk allele rs1333049C was seen in cases (0·60) as compared with controls (0·49), which associated with CAD risk both in univariate (OR = 1·564, 95%CI = 1·154-2·119, P = 0·003) and multivariate analysis (OR = 2·460, 95%CI = 1·139-5·314, P = 0·022). Increased frequency of the risk allele was seen in younger individuals with CAD where 40% individuals in the age group 30-55 years had the CC genotype as compared with 29 and 24·5% in the age group 56-65 years and > 65 years, respectively (CC versus GG, P = 0·045). Higher incidence of the CC genotype was seen in MI patients, but missed significance when compared with controls (OR = 1·361, 95%CI = 0·954-1·942, P = 0·084). In conclusion, the rs1333049 variant is significantly associated with CAD risk and also with age of onset in the Western Indian population. However there are differences in the haplotype structure of this SNP with the neighbouring rs10757278 SNP, these differences emphasize the importance of genotyping all risk variants at this locus which could underlie the differences in risk susceptibility to CAD across populations.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Variant at 9p21 rs1333049 is associated with age of onset of coronary artery disease in a Western Indian population: a case control association study

Bhanushali¹,

Contractor²,

Das³

2013

Genet. Res.

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“…11 The risks associated with genetic variants may decrease with advancing age. 12 Thus, there has been little research on associations between the 9p21 variant and CAD mortality at older ages. 13 In addition, there is little evidence on whether this variant is associated with mortality attributable to stroke.…”

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confidence: 99%

The Coronary Artery Disease–Associated 9p21 Variant and Later Life 20-Year Survival to Cohort Extinction

Dutta

Henley

Lang

et al. 2011

Circ Cardiovasc Genet

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Background Common variation at chromosome 9p21 (marked by rs10757278 or rs1333049) is associated with coronary artery disease (CAD) and peripheral vascular disease. A decreasing effect at older age was suggested, and effects on long-term mortality are unclear. We estimated 9p21 associations with CAD and all-cause mortality in a CAD diagnosis–free older population. We also estimated classification gains on adding the variant to the Framingham Risk Score (FRS) for CAD. Methods and Results DNA was from an Established Populations for Epidemiological Study of the Elderly–Iowa cohort from 1988 (participants >71 years), with death certificates obtained to 2008 for 92% of participants. Cox regression models were adjusted for confounders and CAD risk factors. Of 1095 CAD diagnosis–free participants, 52% were heterozygous (CG) and 22% were homozygous (CC) for the risk C allele rs1333049. Unadjusted CAD-attributed death rates in the CC group were 30 vs 22 per 1000 person-years for the GG group. The C allele was associated with all-cause (hazard ratio, 1.19; 95% CI, 1.08–1.30) and CAD (hazard ratio, 1.29; 95% CI, 1.08–1.56) mortality, independent of CAD risk factors. There was no association with stroke deaths. Variant associations with CAD mortality were attenuated after the age of 80 years (age-interaction term P=0.05). In age group 71 to 80 years, FRS classified as high risk 21% of respondents who died of CAD within 10 years; adding 9p21 identified 27% of respondents. Conclusions In 71- to 80-year-old subjects free of CAD diagnoses, 9p21 is associated with excess mortality, mainly attributed to CAD mortality. Adding 9p21 to the FRS may improve the targeting of CAD prevention in older people, but validation in independent samples is needed for confirmation.

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“…Studies differ in the selection of 9p21 SNPs and the definitions of early-onset disease but uniformly include few women or non-white populations. Chromosome 9p21 SNPs were correlated with early onset CHD in several white (Helgadottir et al, 2007;Abdullah et al, 2008;Meng et al, 2008;Ellis et al, 2010) and Chinese (Chen et al, 2009) populations but not in others (Broadbent et al, 2008;Dehghan et al, 2008). Approximately 25% of whites carry two copies of the 9p21 risk alleles with an estimated risk of early onset CHD that is twice that among individuals without these alleles (McPherson, 2010).…”

Section: Introductionmentioning

confidence: 94%

“…A meta-analysis of studies of Northern Europeans provided compelling evidence linking chromosome 9p21 single-nucleotide polymorphisms (SNPs) and CHD (Schunkert et al, 2008). These associations have been robustly replicated with similar effect sizes and allele frequencies in Japanese and Korean (Hinohara et al, 2008), Irish (Meng et al, 2008), East Indian (Maitra et al, 2009), South Asian (Saleheen et al, 2010), and European (Karvanen et al, 2009) populations. The few studies comprising blacks have found 9p21 variants to be less prevalent than in whites (McPherson et al, 2007;Assimes et al, 2008).…”

Section: Introductionmentioning

confidence: 98%

The Relationship Between Polymorphisms on Chromosome 9p21 and Age of Onset of Coronary Heart Disease in Black and White Women

Beckie

Groer

Beckstead

2011

Genetic Testing and Molecular Biomarkers

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Aim: 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. Results: 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. Conclusions: Different variants on chromosome 9p21 may influence CHD age of onset in whites and blacks.

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Chromosome 9p21.3 is Associated with Early-Onset Coronary Heart Disease in the Irish Population

Cited by 17 publications

References 19 publications

Variant at 9p21 rs1333049 is associated with age of onset of coronary artery disease in a Western Indian population: a case control association study

Variant at 9p21 rs1333049 is associated with age of onset of coronary artery disease in a Western Indian population: a case control association study

The Coronary Artery Disease–Associated 9p21 Variant and Later Life 20-Year Survival to Cohort Extinction

The Relationship Between Polymorphisms on Chromosome 9p21 and Age of Onset of Coronary Heart Disease in Black and White Women

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