Kelly Volcik

Publications (36) View all

• Article: Relation of lipid gene scores to longitudinal trends in lipid levels and incidence of abnormal lipid levels among individuals of European ancestry: the Atherosclerosis Risk in Communities (ARIC) study.

  Pamela L Lutsey, Laura J Rasmussen-Torvik, James S Pankow, Alvaro Alonso, Derek J Smolenski, Weihong Tang, Josef Coresh, Kelly A Volcik, Christie M Ballantyne, Eric Boerwinkle, Aaron R Folsom
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  ABSTRACT: Multiple genetic loci have been associated with blood lipid levels. We tested the hypothesis that persons with an unfavorable lipid gene profile would experience a greater increase in lipid levels and a higher incidence of abnormal lipid levels relative to those with more-favorable lipid gene profiles. A total of 9328 individuals of European descent (aged 45-64 years) in the ARIC (Atherosclerosis Risk in Communities) study were followed for 9 years. Separate gene scores were created for each lipid phenotype on the basis of 95 loci identified in a published genome-wide association study of >100 000 people of European-descent. Adjusted linear and survival models were used to estimate associations with lipid levels and incidence of lipid-lowering medication or abnormal lipid levels. Age and sex interactions were also explored. The cross-sectional difference (mg/dL) per 1 SD was -1.89 for high-density lipoprotein cholesterol (HDL-C), 9.5 for low-density lipoprotein cholesterol (LDL-C), and 22.8 for triglycerides (P<5×10(-34) for all). Longitudinally, overall triglyceride levels rose over time, and each 1-SD greater triglyceride gene score was associated with an average increase in triglyceride levels of 0.3 mg/dL (P=0.003) over 3 years. The HDL-C, LDL-C, and total cholesterol gene scores were not related to change. All lipid gene scores were positively related to incidence of abnormal lipid levels over follow-up (hazard ratios per SD range, 1.15-1.36). Associations of genetic variants with lipid levels over time are complex. The triglyceride gene score was positively related to change in triglycerides levels, but similar longitudinal results were not observed for LDL-C or HDL-C levels. Unfavorable gene scores were nevertheless related to higher incidence of abnormal levels.
  Circulation Cardiovascular Genetics 11/2011; 5(1):73-80. · 6.11 Impact Factor
• Article: Interaction of folate intake and the paraoxonase Q192R polymorphism with risk of incident coronary heart disease and ischemic stroke: the atherosclerosis risk in communities study.

  Hung N Luu, Pascal L Kingah, Kari North, Eric Boerwinkle, Kelly A Volcik
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  ABSTRACT: To investigate the potential interaction between folate intake and the paraoxonase 1 (PON1) Q192R polymorphism with the risk of incident coronary heart disease (CHD) and ischemic stroke in the Atherosclerosis Risk in Communities study, a population-based prospective cohort of cardiovascular disease in 15,792 white and African-American subject. Race-stratified Cox proportional hazards models were performed to examine the interaction between folate intake and the PON1 Q192R polymorphism. A significant inverse association between folate intake and risk of incident CHD among white subjects was found (hazard rate ratio, 1.30; 95% confidence interval, 1.09-1.56; P = .004; folate intake ≤155 μg vs ≥279 μg, reference group). An interaction effect was observed between the dominant genetic model and folate intake with regards to incident ischemic stroke in white subjects (hazard rate ratio, 0.68; 95% confidence interval, 0.91-0.99; and 1.24 from 1st-4th quartile, respectively; P-trend = .05). There was an interaction between folate intake and PON1 Q192 polymorphism with regard to the risk of ischemic stroke in white subjects. Future studies should investigate the interaction between additional polymorphisms within the PON1 gene and genetic variants in other folate metabolizing genes with folate intake on the risk of incident CHD and stroke.
  Annals of epidemiology 11/2011; 21(11):815-23. · 2.95 Impact Factor
• Article: MMP2 genetic variation is associated with measures of fibrous cap thickness: The Atherosclerosis Risk in Communities Carotid MRI Study.

  Kelly A Volcik, Stephen Campbell, Lloyd E Chambless, Josef Coresh, Aaron R Folsom, Thomas H Mosley, Hanyu Ni, Lynne E Wagenknecht, Bruce A Wasserman, Eric Boerwinkle
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  ABSTRACT: Genetic variation in matrix metalloproteinase (MMP) promoter regions alter the transcriptional activity of MMPs and has been consistently associated with CHD, presumably through plaque degradation and remodeling. We examined the association of MMP promoter variation with multiple plaque characteristics measured by gadolinium-enhanced MRI among 1700 participants in the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study. For the analyses presented here, 1700 participants of the biracial ARIC Carotid MRI Study ( approximately 1000 participants with thick carotid artery walls and approximately 700 randomly sampled participants) were evaluated for associations of MMP genetic variation with multiple plaque characteristics, including carotid artery wall thickness, lipid core and fibrous cap measures. MRI studies were performed on a 1.5T scanner equipped with a bilateral 4-element phased array carotid coil. Fifty-one percent of the participants were female, 77% white, 23% African American, and the mean age was 70 years. MMP2 C-1306T variant genotypes (CT+TT) were significantly associated with higher cap thickness measures, but not with wall thickness or lipid core measures. Individuals with the CC genotype had approximately 0.1mm thinner cap thickness compared to those carrying a T allele (P=0.02). Genetic variation within the MMP2 promoter region was associated with cap thickness and therefore may influence the role of MMP2 in plaque vulnerability.
  Atherosclerosis 05/2010; 210(1):188-93. · 3.79 Impact Factor
• Article: Intercellular adhesion molecule-1 G241R polymorphism predicts risk of incident ischemic stroke: Atherosclerosis Risk in Communities study.

  Kelly A Volcik, Christie M Ballantyne, Ron Hoogeveen, Aaron R Folsom, Eric Boerwinkle
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  ABSTRACT: BACKGROUND AND PURPOSE: Intercellular adhesion molecule-1 levels are increased in pathological studies of atherosclerosis. We evaluated 13 491 participants from the Atherosclerosis Risk in Communities Study to determine the association of intercellular adhesion molecule-1 G241R and K469E polymorphisms with incident coronary heart disease and ischemic stroke. METHODS: Incidences of ischemic stroke (N=517) and coronary heart disease (N=1629) through 2003 were determined by annual telephone calls and hospital and death certificate surveillance. Risk factors were measured at the baseline examination. Cox proportional-hazards models were used to estimate hazard rate ratios. RESULTS: The intercellular adhesion molecule-1 G241RR genotype was associated with a significantly increased risk of ischemic stroke in both whites (hazard rate ratio=2.18; 95% CI, 1.01 to 4.68; P=0.05) and blacks (hazard rate ratio=7.04; 95% CI, 3.72 to 13.3; P<0.001). CONCLUSIONS: The intercellular adhesion molecule-1 241RR genotype is associated with an increased risk of incident ischemic stroke in both whites and blacks.
  Stroke 04/2010; 41(5):1038-40. · 5.73 Impact Factor
• Article: Diabetes genes and prostate cancer in the Atherosclerosis Risk in Communities study.

  Tamra E Meyer, Eric Boerwinkle, Alanna C Morrison, Kelly A Volcik, Maureen Sanderson, Ann L Coker, James S Pankow, Aaron R Folsom
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  ABSTRACT: There is a known inverse association between type 2 diabetes (T2D) and prostate cancer (PrCa) that is poorly understood. Genetic studies of the T2D-PrCa association may provide insight into the underlying mechanisms of this association. We evaluated associations in the Atherosclerosis Risk in Communities study between PrCa and nine T2D single nucleotide polymorphisms from genome-wide association studies of T2D (in CDKAL1, CDKN2A/B, FTO, HHEX, IGF2BP2, KCNJ11, PPARG, SLC30A8, and TCF7L2) and four T2D single nucleotide polymorphisms from pre-genome-wide association studies (in ADRB2, CAPN10, SLC2A2, and UCP2). From 1987 to 2000, there were 397 incident PrCa cases among 6,642 men ages 45 to 64 years at baseline. We used race-adjusted Cox proportional hazards models to estimate associations between PrCa and increasing number of T2D risk-raising alleles. PrCa was positively associated with the CAPN10 rs3792267 G allele [hazard ratio (HR) 1.20; 95% confidence interval (CI), 1.00-1.44] and inversely associated with the SLC2A2 rs5400 Thr110 allele (HR, 0.85; 95% CI, 0.72, 1.00), the UCP2 rs660339 Val55 allele (HR, 0.84; 95% CI, 0.73, 0.97) and the IGF2BP2 rs4402960 T allele (HR, 0.79; 95% CI, 0.61-1.02; blacks only). The TCF7L2 rs7903146 T allele was inversely associated with PrCa using a dominant genetic model (HR, 0.79; 95% CI, 0.65-0.97). Further knowledge of T2D gene-PrCa mechanisms may improve understanding of PrCa etiology.
  Cancer Epidemiology Biomarkers &amp Prevention 02/2010; 19(2):558-65. · 4.12 Impact Factor