James C Devlin | North Idaho College (original) (raw)

Papers by James C Devlin

Other by James C Devlin

Journal of the American College of Cardiology, 2008

We asked whether 35 genetic polymorphisms, previously found to be associated with cardiovascular ... more We asked whether 35 genetic polymorphisms, previously found to be associated with cardiovascular disease, were associated with myocardial infarction (MI) in the CARE (Cholesterol and Recurrent Events) trial and with coronary heart disease (CHD) in the WOSCOPS (West of Scotland Coronary Prevention Study) trial and whether the risk associated with these polymorphisms could be reduced by pravastatin treatment.

Haematologica, 2009

We recently reported the association between the Malmö sequence variant in F9 (rs6048) and deep v... more We recently reported the association between the Malmö sequence variant in F9 (rs6048) and deep vein thrombosis.

Human Genetics, 2011

A single nucleotide polymorphism (SNP) in KIF6, a member of the KIF9 family of kinesins, is assoc... more A single nucleotide polymorphism (SNP) in KIF6, a member of the KIF9 family of kinesins, is associated with diVerential coronary event reduction from statin therapy in four randomized controlled trials; this SNP (rs20455) is also associated with the risk for coronary heart disease (CHD) in multiple prospective studies. We investigated whether other common SNPs in the KIF6 region were associated with event reduction from statin therapy. Of the 170 SNPs in the KIF6 region investigated in the Cholesterol and Recurrent Events trial (CARE), 28 were associated with diVerential event reduction from statin therapy (P interaction < 0.1 in Caucasians, adjusted for age and sex) and were further investigated in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI22) and West of Scotland Coronary Prevention Study (WOSCOPS).

European Journal of Cardiovascular Prevention & Rehabilitation, 2010

Statin therapy has been found to substantially and significantly reduce coronary events in carrie... more Statin therapy has been found to substantially and significantly reduce coronary events in carriers of the KIF6 719Arg variant (rs20455) but not in noncarriers. We investigated whether, among the elderly, statin therapy also significantly reduced coronary events in carriers but not in noncarriers. Among 5,752 patients of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study, we assessed the effect of pravastatin, compared with placebo, on coronary events according to 719Arg carrier status using proportional hazards models. Since benefit from statin therapy in elderly patients has been primarily shown among those with prior vascular disease, we performed analyses in PROSPER patients with prior disease and found that pravastatin therapy significantly reduced events in 719Arg carriers [hazards ratio (HR): 0.66, 95% confidence interval (CI): 0.52-0.86] but not in noncarriers (HR: 0.94, 95% CI: 0.69-1.28), P=0.09 for interaction between treatment and carrier status. Among those without prior disease, no significant benefit was observed in either carriers or noncarriers. Among those with prior vascular disease in the placebo arm, Trp719Arg heterozygotes were at significantly greater risk, compared with noncarriers (HR: 1.36, 95% CI: 1.03-1.81, P=0.03); the HR of 719Arg carriers, compared with noncarriers, was 1.28 (95% CI: 0.98-1.69, P=0.07). Elderly carriers of the KIF6 719Arg variant with prior vascular disease received significant benefit from pravastatin therapy; no benefit was observed in noncarriers with prior disease or in those without prior disease (carriers or noncarriers).

Genetics in Medicine, 2007

Because multiple genetic variants influence risk for coronary heart disease, we combined multiple... more Because multiple genetic variants influence risk for coronary heart disease, we combined multiple variants that had been associated with coronary heart disease in several studies into a genetic risk score and asked whether a high genetic risk score would be significantly associated with coronary heart disease after accounting for traditional risk factors. We considered five variants that were associated with coronary heart disease in two studies and confirmed in the Atherosclerosis Risk in Communities study: rs20455 (KIF6), rs3900940 (MYH15), rs7439293 (PALLD), rs2298566 (SNX19), and rs1010 (VAMP8). We calculated a genetic risk score for each Atherosclerosis Risk in Communities study participant and estimated the hazard ratio for incident coronary heart disease of a high genetic risk score (compared with not-high) in Cox models that adjusted for traditional risk factors during a median of 13 years of follow-up. For white participants with a high genetic risk score (4% of the 9129 whites), compared with those without a high genetic risk score, the hazard ratio for incident coronary heart disease was 1.57 (95% confidence interval 1.21-2.04; P = 0.001). Internal validation using bootstrap samples estimated that a hazard ratio of 1.43 could be expected in external populations. After adjusting for traditional risk factors, those with a high genetic risk score had a 57% increased risk of incident coronary heart disease in the Atherosclerosis Risk in Communities study.

Drug Development Research, 1996

ABSTRACT A matrix-based compound pooling and deconvolution method has been developed that signifi... more ABSTRACT A matrix-based compound pooling and deconvolution method has been developed that significantly increased the efficiency of a high-capacity screening program. This method is based on screening pools of 10 compounds. The matrix used to assemble the pools ...

Drug Development Research, 1998

ABSTRACT A high-throughput, nonradioactive telomerase assay using a europium-labeled oligonucle-o... more ABSTRACT A high-throughput, nonradioactive telomerase assay using a europium-labeled oligonucle-otide probe and time-resolved fluorescence has been developed to detect PCR-amplified telomerase prod-ucts. The use of a thermally activated TAQ polymerase, rather than a ...

BMC Cardiovascular Disorders, 2011

Background: Genetic risk factors might improve prediction of coronary events. Several variants at... more Background: Genetic risk factors might improve prediction of coronary events. Several variants at chromosome 9p21.3 have been widely reported to be associated with coronary heart disease (CHD) in prospective and casecontrol studies. A variant of KIF6 (719Arg) has also been reported to be associated with increased risk of CHD in large prospective studies, but not in case-control studies. We asked whether the addition of genetic information (the 9p21.3 or KIF6 variants) or a well-established non-genetic risk factor (C-reactive protein [CRP]) can improve risk prediction by the Framingham Risk Score (FRS) in the Cardiovascular Health Study (CHS)-a prospective observational study of risk factors for cardiovascular disease among > 5,000 participants aged 65 or older. Methods: Improvement of risk prediction was assessed by change in the area under the receiver-operator characteristic curve (AUC) and by net reclassification improvement (NRI). Results: Among white participants the FRS was improved by addition of KIF6 719Arg carrier status among men as assessed by the AUC (from 0.581 to 0.596, P = 0.03) but not by NRI (NRI = 0.027, P = 0.32). Adding both CRP and 719Arg carrier status to the FRS improved risk prediction by the AUC (0.608, P = 0.02) and NRI (0.093, P = 0.008) in men, but not women (P ≥ 0.24). Conclusions: While none of these risk markers individually or in combination improved risk prediction among women, a combination of KIF6 719Arg carrier status and CRP levels modestly improved risk prediction among white men; although this improvement is not significant after multiple-testing correction. These observations should be investigated in other prospective studies.

Cerebrovascular Diseases, 2012

Cardiovascular Pathology, 2004

Family history of coronary heart disease is an independent risk for myocardial infarction Few... more Family history of coronary heart disease is an independent risk for myocardial infarction Few genetic risk markers have been identified so far We tested ~9,000 putative functional SNPs for association with MI We present associations that are replicated in two independent ...

Atherosclerosis, 2009

Objective: A minor allele variant (rs3798220) of apolipoprotein(a) has been reported to be associ... more Objective: A minor allele variant (rs3798220) of apolipoprotein(a) has been reported to be associated with elevated plasma lipoprotein(a) [Lp(a)] and increased cardiovascular risk. We investigated whether this allele was associated with elevated Lp(a) and cardiovascular risk in the Women's Health Study, a randomized trial of low-dose aspirin, and whether aspirin reduced cardiovascular risk in minor allele carriers. Methods and results: Genotypes of rs3798220 were determined for 25,131 initially healthy Caucasian participants. Median Lp(a) levels at baseline were 10.0, 79.5, and 153.9 mg/dL for major allele homozygotes, heterozygotes, and minor allele homozygotes, respectively (P < 0.0001). During the 9.9 years of follow-up, minor allele carriers (3.7%) in the placebo group had twofold higher risk of major cardiovascular events than non-carriers (age-adjusted hazard ratio (HR) = 2.21, 95% CI: 1.39-3.52). Among carriers, risk was reduced more than twofold by aspirin: for aspirin compared with placebo the age-adjusted HR was 0.44 (95% CI: 0.20-0.94); risk was not significantly reduced among non-carriers (age-adjusted HR = 0.91, 95% CI: 0.77-1.08). This interaction between carrier status and aspirin allocation was significant (P = 0.048). Conclusions: In the Women's Health Study, carriers of an apolipoprotein(a) variant had elevated Lp(a), doubled cardiovascular risk, and appeared to benefit more from aspirin than non-carriers.

Atherosclerosis, 2010

Objective: LPA encodes apolipoprotein(a), and a CCTC haplotype in the LPA locus is associated wit... more Objective: LPA encodes apolipoprotein(a), and a CCTC haplotype in the LPA locus is associated with CHD. The 4399Met variant (rs3798220) of LPA has a risk estimate for CHD similar to that of the CCTC haplotype. We asked whether co-incidence with the 4399Met variant explained the association of the haplotype with CHD. Methods: We stratified by the 4399Met variant and another LPA SNP (rs10455872) associated with CHD and tested the association between CHD and 4 SNPs that define two haplotypes associated with CHD: CCTC and CTTG. Results: For CCTC, in the presence of the rs3798220 risk allele the OR was 1.68 (95% CI: 1.05-2.68, P = 0.03) versus 0.30 (95% CI: 0.06-1.59, P = 0.16) with the non-risk allele. For CTTG, in the presence of the rs10455872 risk allele the OR was 1.57 (95% CI: 1.15-2.13, P = 0.004) versus 1.04 (95% CI: 0.79-1.35, P = 0.77) with the non-risk allele. Conclusion: The rs3798220 and rs10455872 SNPs explain the association of the CCTC and CTTG haplotypes with CHD.

Arteriosclerosis, Thrombosis, and Vascular Biology, 2006

Methods and Results-We tested 11 647 single-nucleotide polymorphisms (SNPs) for association with ... more Methods and Results-We tested 11 647 single-nucleotide polymorphisms (SNPs) for association with early-onset MI in a case-control study (study 1 200 cases, 262 controls). To reduce the number of false positives among the 666 SNPs that were nominally associated with early-onset MI (PϽ0.05) in study 1, we tested these SNPs in study 2 (434 cases, 504 controls). We found that 8 of the 666 SNPs were associated with early-onset MI in study 2 (PϽ0.05) and had the same risk alleles as in study 1. These 8 SNPs were then tested for association with early-onset MI in study 3 (187 cases, 434 controls). We found that a VAMP8 variant (Pϭ0.025; odds ratio [OR], 1.75; CI, 1.17 to 2.62) and an HNRPUL1 variant (Pϭ0.0043; OR, 1.92; CI, 1.28 to 2.86) were associated with early-onset MI (nominal PϽ0.05; false discovery rate Ͻ10%) and had the same risk alleles in all 3 studies. Conclusions-Variants in 2 genes were associated with early-onset MI: VAMP8, which is involved in platelet degranulation, and HNRPUL1, which encodes a ribonuclear protein. The identification of these variants could improve understanding of disease mechanisms and suggest novel drug targets. (Arterioscler Thromb Vasc Biol. 2006;26:1613-1618.)

Arteriosclerosis, Thrombosis, and Vascular Biology, 2006

Data Supplement (unedited) at: http://atvb.ahajournals.org located on the World Wide Web at:

Arteriosclerosis, Thrombosis, and Vascular Biology, 2008

Objective-The purpose of this study was to investigate the association between the Ala 227 Pro po... more Objective-The purpose of this study was to investigate the association between the Ala 227 Pro polymorphism in the ADAMTS1 metalloproteinase gene and coronary heart disease and benefit from statin therapy in 2 independent cohorts. Methods and Results-The frequency of the ADAMTS1 227 Pro minor allele was 0.24 in 2421 male subjects from CARE, a randomized trial of pravastatin versus placebo. In the placebo arm, homozygotes (6.3% of study population) had a significantly increased risk of fatal coronary disease or nonfatal myocardial infarction (D/MI) compared with noncarriers (OR 2.12, 95% CI 1.07 to 4.19, Pϭ0.03), and in the entire study the benefit of pravastatin in reducing the risk of D/MI was greater in these subjects (OR 0.21, 95% CI 0.06 to 0.69) than in heterozygotes (OR 0.74, 95% CI 0.48 to 1.14) or noncarriers (OR 0.99, 95% CI 0.68 to 1.42; P interaction ϭ0.044). Results were tested in 1565 male subjects from WOSCOPS, also a randomized trial of pravastatin versus placebo. Similar to the results in CARE, in the placebo arm subjects homozygous for the minor allele were at increased risk of D/MI (OR 1.72, Pϭ0.052) and in the entire study the benefit of pravastatin in reducing D/MI was greater in these subjects (OR 0.24, 95% CI 0.09 to 0.68) than in heterozygotes (OR 0.73, 95% CI 0.48 to 1.11) or noncarriers (OR 0.65, 95% CI 0.20 to 2.09) (P interaction ϭ0.029). Conclusions-In men not on pravastatin, those homozygous for the 227 Pro allele of ADAMTS1 have a nearly 2-fold increased risk of coronary heart disease events compared with noncarriers. In this high-risk group, treatment with pravastatin is highly efficacious, reducing the odds of fatal coronary disease or nonfatal MI by approximately 75%, as compared with 25% in noncarriers or heterozygotes. (Arterioscler Thromb Vasc Biol. 2008;28:562-567)

Arteriosclerosis, Thrombosis, and Vascular Biology, 2007

Objective-We asked whether single nucleotide polymorphisms (SNPs) that had been nominally associa... more Objective-We asked whether single nucleotide polymorphisms (SNPs) that had been nominally associated with cardiovascular disease in antecedent studies were also associated with cardiovascular disease in a population-based prospective study of 4522 individuals aged 65 or older. Methods and Results-Based on antecedent studies, we prespecified a risk allele and an inheritance model for each of 74

American Journal of Obstetrics and Gynecology, 2009

To determine the effects of cigarette smoke on cell growth, an immortalized trophoblast cell line... more To determine the effects of cigarette smoke on cell growth, an immortalized trophoblast cell line (HTRB/SV-NEO) was treated with increasing doses of CSE or nicotine. Cell viability assays were performed at 24 and 48 hours. In addition, total RNA was isolated from 1% and 15% CSE treated trophoblast cells at 2, 4, 8, and 24 hours and cDNA generated, followed by real time PCR gene quantification of ADM, sFlt-1, and VEGF. Data were normalized to GAPDH expression and relative expression values calculated. RESULTS: At 24 hours, cells treated with CSE were significantly different compared to untreated controls or those treated with nicotine alone (ANOVA, pϽ0.001, ). By real time PCR, ADM and sFlt-1 were significantly up-regulated (Ͼ30 fold, pϽ.03) with CSE treatment (1% and 15%). There were no differences in VEGF expression at any time point.

Arteriosclerosis, Thrombosis, and Vascular Biology, 2007

Objectives-The purpose of this study was to identify genetic variants associated with severe coro... more Objectives-The purpose of this study was to identify genetic variants associated with severe coronary artery disease (CAD). Methods and Results-We used 3 case-control studies of white subjects whose severity of CAD was assessed by angiography. The first 2 studies were used to generate hypotheses that were then tested in the third study. We tested 12 077 putative functional single nucleotide polymorphisms (SNPs) in Study 1 (781 cases, 603 controls) and identified 302 SNPs nominally associated with severe CAD. Testing these 302 SNPs in Study 2 (471 cases, 298 controls), we found 5 (in LPA, CALM1, HAP1, AP3B1, and ABCG2) were nominally associated with severe CAD and had the same risk alleles in both studies. We then tested these 5 SNPs in Study 3 (554 cases, 373 controls). We found 1 SNP that was associated with severe CAD: LPA I4399M (rs3798220). LPA encodes apolipoprotein(a), a component of lipoprotein(a). I4399M is located in the protease-like domain of apolipoprotein(a). Compared with noncarriers, carriers of the 4399M risk allele (2.7% of controls) had an adjusted odds ratio for severe CAD of 3.14 (confidence interval 1.51 to 6.56), and had 5-fold higher median plasma lipoprotein(a) levels (Pϭ0.003).

The American Journal of Human Genetics, 2005

Family history is a major risk factor for myocardial infarction (MI). However, known gene variant... more Family history is a major risk factor for myocardial infarction (MI). However, known gene variants associated with MI cannot fully explain the genetic component of MI risk. We hypothesized that a gene-centric association study that was not limited to candidate genes could identify novel genetic associations with MI. We studied 11,053 single-nucleotide polymorphisms (SNPs) in 6,891 genes, focusing on SNPs that could influence gene function to increase the likelihood of identifying disease-causing gene variants. To minimize false-positive associations generated by multiple testing, two studies were used to identify a limited number of nominally associated SNPs; a third study tested the hypotheses that these SNPs are associated with MI. In the initial study (of 340 cases and 346 controls), 637 SNPs were associated with MI ( ); these were evaluated in a second study (of 445 cases and 606 controls), P ! .05 and 31 of the 637 SNPs were associated with MI ( ) and had the same risk allele as in the first study. For P ! .05 each of these 31 SNPs, we tested the hypothesis that it is associated with MI, using a third study (of 560 cases and 891 controls). We found that four of these gene variants were associated with MI ( ; false-discovery rate P ! .05 !10%) and had the same risk allele as in the first two studies. These gene variants encode the cytoskeletal protein palladin (KIAA0992 [odds ratio (OR) 1.40]), a tyrosine kinase (ROS1 [OR 1.75]), and two G protein-coupled receptors (TAS2R50 [OR 1.58] and OR13G1 [OR 1.40]); all ORs are for carriers of two versus zero risk alleles. These findings could lead to a better understanding of MI pathophysiology and improved patient risk assessment.

Journal of the American College of Cardiology, 2008

Haematologica, 2009

Human Genetics, 2011

European Journal of Cardiovascular Prevention & Rehabilitation, 2010

Genetics in Medicine, 2007

Drug Development Research, 1996

Drug Development Research, 1998

BMC Cardiovascular Disorders, 2011

Cerebrovascular Diseases, 2012

Cardiovascular Pathology, 2004

Atherosclerosis, 2009

Atherosclerosis, 2010

Arteriosclerosis, Thrombosis, and Vascular Biology, 2006

Data Supplement (unedited) at: http://atvb.ahajournals.org located on the World Wide Web at:

Arteriosclerosis, Thrombosis, and Vascular Biology, 2008

Arteriosclerosis, Thrombosis, and Vascular Biology, 2007

American Journal of Obstetrics and Gynecology, 2009

Arteriosclerosis, Thrombosis, and Vascular Biology, 2007

The American Journal of Human Genetics, 2005

American Journal of Epidemiology, 2007

Recent studies have evaluated whether incorporating nontraditional risk factors improves coronary... more Recent studies have evaluated whether incorporating nontraditional risk factors improves coronary heart disease (CHD) prediction models. This 1986-2001 US study aggregated the contribution of multiple single nucleotide polymorphisms into a genetic risk score (GRS) and assessed whether the GRS plus traditional risk factors predict CHD better than traditional risk factors alone. The Atherosclerosis Risk in Communities (ARIC) cohort was followed for a median of 13 years for CHD events (n ¼ 1,452). Individuals were genotyped for 116 single nucleotide polymorphisms associated with CHD in multiple case-control studies. Single nucleotide polymorphisms nominally predicting incident CHD in the ARIC study were included in the GRS. The GRS was significantly associated with incident CHD in Blacks (hazard rate ratio ¼ 1.20, 95% confidence interval: 1.11, 1.29) and Whites (hazard rate ratio ¼ 1.10, 95% confidence interval: 1.06, 1.14) as well as in each tertile defined by the traditional cardiovascular risk score (p 0.02). When receiver operating characteristic curves based on traditional risk factors were recalculated after the GRS was added, the increase in the area under the receiver operating characteristic curve was statistically significant for Blacks and suggestive of improved CHD prediction for Whites. This study demonstrates the concept of aggregating information from multiple single nucleotide polymorphisms into a risk score and indicates that it can improve prediction of incident CHD in the ARIC study. cardiovascular diseases; genetics; polymorphism, genetic; risk factors Abbreviations: ACRS, ARIC Cardiovascular Risk Score; ARIC, Atherosclerosis Risk in Communities; AUC, area under the curve; CHD, coronary heart disease; GRS, genetic risk score; SNP, single nucleotide polymorphism.