Abstract 178: RCBTB1 Genotypes Modulate Smoking Effect on Carotid Intima-Media Thickness: A Finding from a Genome-Wide Interaction Analysis

Objective: Smoking is an established risk factor for atherosclerotic disease. However, the degree of the cigarette smoking-induced damage varies from individual to individual, partly due to the between-individual difference in genetic makeup. The aim of this study was to identify genetic loci influencing the effect of cigarette smoking on carotid intima-media thickness (IMT) by performing a genome-wide association smoking-by-SNP interaction analysis. Methods and results: Genome-wide genotyping was performed using the Affymetrix SNP array 6.0 among 1,010 individuals who underwent B-mode ultrasound examination of carotid IMT from the population-based Northern Manhattan Study. Cigarette pack-years was calculated as number of years smoked multiplied by number of cigarettes smoked per day, then divided by 20. After quality control, a total of 722,379 single nucleotide polymorphisms (SNPs) were included in the final analysis. Generalized linear modeling was conducted to look for smoking-by-SNP interaction on carotid IMT while controlling for age, sex, hypertension, diabetes, dyslipidemia, body mass index, waist-to-hip ratio, and the top 3 principal components estimated to capture ancestry by EIGENSTRAT. Ten SNPs near or within 5 genes showed an interactive effect with cigarette smoking on IMT with a p value <1.0E-5. Among them, 3 SNPs (including 1 exonic splice enhancer SNP rs3751283, P=8.3E-7) are near or within regulator of chromosome condensation and BTB domain containing protein 1 (RCBTB1) gene on 13q14. Specifically, for SNP rs3751283, the mean IMT was substantially increased among CC-carriers (0.70 mm, 0.76 mm, 0.81 mm for 0, <20, and ≥20 cigarette pack-years, respectively, P=2.6E-6), slightly increased with smoking pack-years among TC-carriers (0.72 mm, 0.74 mm, 0.75 mm for 0, <20, and ≥20 cigarette pack-years, respectively, P=0.03), but very similar (0.73 mm) among TT-carriers for the three smoking groups (P=0.84). Conclusion: Our genome-wide interaction analysis reveals multiple genes, especially RCBTB1, that may modify the effect of smoking on carotid IMT. These genes will be further evaluated in our full dataset with additional genotyping. Also, larger independent studies are needed to validate these findings.

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Genetic variants in LEKR1 and GALNT10 modulate sex-difference in carotid intima-media thickness: A genome-wide interaction study

Atherosclerosis ◽

10.1016/j.atherosclerosis.2015.04.019 ◽

2015 ◽

Vol 240 (2) ◽

pp. 462-467 ◽

Cited By ~ 14

Author(s):

Chuanhui Dong ◽

David Della-Morte ◽

Ashley Beecham ◽

Liyong Wang ◽

Digna Cabral ◽

...

Keyword(s):

Sex Difference ◽

Genetic Variants ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Interaction Study ◽

Media Thickness ◽

Genome Wide ◽

A Genome

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Identification of a 3′‐Untranslated Genetic Variant of RARB Associated With Carotid Intima‐Media Thickness in Rheumatoid Arthritis: A Genome‐Wide Association Study

Arthritis & Rheumatology ◽

10.1002/art.40734 ◽

2019 ◽

Vol 71 (3) ◽

pp. 351-360 ◽

Cited By ~ 8

Author(s):

Raquel López‐Mejías ◽

F. David Carmona ◽

Fernanda Genre ◽

Sara Remuzgo‐Martínez ◽

Carlos González‐Juanatey ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Association Study ◽

Genetic Variant ◽

Genome Wide Association Study ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Genome Wide Association ◽

Media Thickness ◽

Genome Wide ◽

A Genome

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Abstract P218: Carotid Intima-media Thickness and Incident End-stage Renal Disease: The Atherosclerosis Risk in Communities Study

Circulation ◽

10.1161/circ.133.suppl_1.p218 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Yuanjie Pang ◽

Yingying Sang ◽

Shoshana Ballew ◽

Morgan Grams ◽

Gerardo Heiss ◽

...

Keyword(s):

Renal Disease ◽

Kidney Function ◽

End Stage Renal Disease ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Carotid Imt ◽

Media Thickness ◽

Hazard Ratios ◽

Stage Renal Disease ◽

End Stage

Introduction: Carotid intima-media thickness (IMT) has been reported to predict kidney function decline. However, whether carotid IMT is associated with a hard kidney endpoint, end-stage renal disease (ESRD), has not been investigated. Hypothesis: We assessed the hypothesis that increased carotid IMT is associated with ESRD risk. Methods: We studied 13,197 ARIC participants at visit 1 (1987-1989) without history of cardiovascular disease including coronary heart disease, stroke and heart failure and assessed whether carotid IMT measured by B-mode ultrasound is associated with ESRD risk using Cox proportional-hazards models. Regarding carotid IMT parameters, we investigated the mean and maximum values of overall and segment-specific (common, bifurcation and internal carotid arteries) measurements. Results: Mean age was 54.0 (SD 5.7) years, and there were 3,373 (25.6%) blacks and 7,370 (55.8%) women. During a median follow-up of 22.7 years, 433 participants developed ESRD (1.4/1,000 person-years). After adjusting for shared risk factors for atherosclerosis and kidney disease, including baseline kidney function, carotid IMT was significantly associated with ESRD risk (hazard ratios between quartiles 4 and 1, 1.43 [95%CI: 1.01-2.04] for overall mean IMT and 1.73 [95%CI: 1.22-2.44] for overall maximum IMT). The associations were largely consistent in demographic and clinical subgroups. When we explored segment-specific IMTs, the associations with ESRD were most robust for bifurcation carotid. The adjusted hazard ratios between quartiles 4 and 1 were 1.48 (95%CI: 1.04-2.11) for mean bifurcation IMT and 1.42 (95%CI: 0.99-2.03) for maximum bifurcation IMT. Conclusions: Carotid IMT was independently associated with incident ESRD in the general population. Our findings suggest the shared etiology between atherosclerosis and ESRD and highlight the importance of monitoring kidney function over time in individuals with subclinical atherosclerosis.

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Common femoral artery intima-media thickness as marker for cardiovascular disease in asymptomatic adults

VASA ◽

10.1024/0301-1526.38.2.147 ◽

2009 ◽

Vol 38 (2) ◽

pp. 147-154 ◽

Cited By ~ 7

Author(s):

Giannoukas ◽

Antoniou ◽

Saleptsis ◽

Baros ◽

Griffin ◽

...

Keyword(s):

Cardiovascular Disease ◽

Risk Score ◽

Density Lipoprotein ◽

Intima Media Thickness ◽

Common Femoral Artery ◽

Carotid Intima Media Thickness ◽

Carotid Imt ◽

Media Thickness ◽

Similar Correlation ◽

The Common

Background: The common carotid intima-media thickness (IMT) is considered as a marker of cardiovascular disease, while the value of the common femoral IMT is not well defined. The aim of the present study was to investigate the value of common femoral IMT alone or in combination with the common carotid IMT as a marker of cardiovascular disease in asymptomatic adults. Patients and Methods: Eighty-three individuals with no history of cardiovascular disease were subjected to IMT measurement of both common carotid and common femoral arteries with high-resolution ultrasonography. The Framingham Heart Study (FHS) risk score was calculated for each subject (according to gender) and was correlated with the carotid IMT, femoral IMT, and the combined IMT measured at both arterial sites. Results: The carotid and femoral IMT separately and in combination were found to be correlated with the FHS risk score, calculated based on either the total cholesterol or low density lipoprotein plasma levels (carotid IMT: r = 0.28, p = 0.035, and r = 0.35, p = 0.007, respectively, femoral IMT: r = 0.38, p = 0.003, and r = 0.43, p = 0.001, respectively, carotid-femoral IMT: r = 0.37, p = 0.005, and r = 0.46, p = 0.0001, respectively). In addition, femoral IMT was found to be correlated with the carotid IMT (r = 0.41, p = 0.001). Conclusions: Common carotid and common femoral IMT showed similar correlation with the FHS risk score. Additionally, the combination of IMT from both arterial sites was found to have similar correlation with the FHS risk score to carotid IMT alone.

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Are Uremia, Diabetes, and Atherosclerosis Linked With Impaired Antioxidant Mechanisms?

Journal of Investigative Medicine ◽

10.2310/jim.0b013e3181641ce3 ◽

2008 ◽

Vol 56 (2) ◽

pp. 545-552 ◽

Cited By ~ 13

Author(s):

Belda Dursun ◽

Evrim Dursun ◽

Irfan Capraz ◽

Tomris Ozben ◽

Ali Apaydin ◽

...

Keyword(s):

Oxidative Stress ◽

Intima Media Thickness ◽

Chronic Kidney Failure ◽

Carotid Intima Media Thickness ◽

Diabetic Patients ◽

Carotid Imt ◽

Accelerated Atherosclerosis ◽

Media Thickness ◽

Diabetes Status ◽

Antioxidant Mechanisms

BackgroundOxidative stress is a new risk factor for atherosclerosis. Increased oxidative stress in hemodialysis (HD) patients may arise from uremia-associated metabolic/humoral abnormalities and bioincompatibility of dialysis. Patients with diabetes mellitus (DM) may be subject to an additional risk. Respective influences of uremia, diabetes, and HD duration in accelerated atherosclerosis and oxidative stress have not been clarified yet.MethodsThe study was performed on 24 nondiabetic HD patients, 23 diabetic HD patients, 20 stages 3 to 4 chronic kidney disease patients, and 21 diabetic patients without overt nephropathy. Carotid intima-media thickness, a surrogate of atherosclerosis, was measured by high-resolution B-mode ultrasonography. Oxidant status was determined by lipid peroxidation as expressed by malondialdehyde (MDA); antioxidant status was determined by superoxide dismutase, catalase, glutathione peroxidase, reduced intracellular glutathione, and plasma thiol.ResultsIntima-media thickness (IMT) was higher in patients undergoing HD but not different between nondiabetic HD patients and diabetic HD patients. No correlation was found between the duration of HD and intima-media thickness. Antioxidants were generally lower in HD patients. Intima-media thickness was positively correlated with MDA and negatively correlated with plasma thiol. Among other risk factors, only age was correlated with intima-media thickness.ConclusionsIncreased carotid IMT in HD patients is independent of duration of HD or diabetes status. Age and MDA are the significant predictors of carotid IMT. Increased oxidative stress due to impaired antioxidant mechanisms, particularly reduced plasma thiol redox potential, may account for accelerated atherosclerosis in high-risk patients with chronic kidney failure and/or DM.

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