Osteopontin Promoter Polymorphism Is Associated With Increased Carotid Intima-Media Thickness

Fuentes, Lisa de las; Gu, C. Charles; Mathews, Santhosh Jay; Reagan, Joann L; Ruthmann, Nicholas; Waggoner, Alan D.; Lai, Chung Fang; Towler, Dwight A.; Dávila‐Román, Víctor G.

doi:10.1016/j.echo.2008.02.005

Cited by 25 publications

(21 citation statements)

References 53 publications

(30 reference statements)

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“…Some previous investigators measured serum or urine OPN levels, and evaluated the association with functional polymorphisms in OPN promoter. 43,44 Indeed, none of them demonstrated significant differences in OPN levels between respective haplotypes, despite observed association with diseases. Presumably, not serum OPN levels, but local expression of OPN might be important to the onset of those disorders.…”

Section: Study Limitationsmentioning

confidence: 91%

Association between osteopontin promoter variants and diastolic dysfunction in hypertensive heart in the Japanese population

et al. 2011

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Heart failure with preserved ejection fraction is recently highlighted as a major health problem, and diastolic dysfunction associated with hypertension has a dominant role in the development of heart failure with preserved ejection fraction. Osteopontin (OPN) is a secreted phosphoprotein, which mediates fibrosis. In animal models, OPN is upregulated in response to pressure overload and is thought to be involved in systolic dysfunction. However, the functional role of OPN in diastolic dysfunction is unknown. The guanine base insertion polymorphism at À156 position of the OPN promoter is postulated to upregulate the transcription of OPN in human. To investigate whether À156del/G polymorphism of OPN promoter is associated with diastolic dysfunction in hypertensive hearts, the patients with hypertension have been genotyped for variants of À156del/G polymorphism by genomic sequencing. Diastolic function of the left ventricle was estimated as the ratio of early to atrial filling (E/A ratio), obtained by pulsed-Doppler derived transmitral flow in echocardiographic analysis. The patients with À156G allele displayed lower E/A ratio compared with those with À156del/del genotype, suggesting exacerbated diastolic function. Notably, in case of the population with diabetes mellitus, the patients with À156G allele showed significant association with lower E/A ratio, compared with À156del/À156del patients. Multiple linear regression analysis revealed that prevalence of À156G allele was an independent factor for lowering E/A ratio. The À156del/G genetic variants of OPN promoter were associated with decreased E/A ratio in hypertensive patients. These results suggest that OPN has a functional role in the development of diastolic dysfunction in hypertensive hearts.

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Section: Study Limitationsmentioning

confidence: 91%

Association between osteopontin promoter variants and diastolic dysfunction in hypertensive heart in the Japanese population

et al. 2011

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“…Genetic variation in the OPN gene was previously associated with susceptibility to diseases such as multiple sclerosis, systemic lupus erythematosus, carotid artery disease, nephrolithiasis, pseudoxanthoma elasticum and several others [8,[24][25][26][27][28]. A possible association of variation in the OPN gene with sarcoidosis in the Japanese population was investigated by Akahoshi et al, who studied a single (2514C/T) polymorphism in the OPN gene but failed to demonstrate any significant association with sarcoidosis in their study sample [29].…”

Section: Discussionmentioning

confidence: 99%

Genetic Variation in Osteopontin Gene Is Associated with Susceptibility to Sarcoidosis in Slovenian Population

et al. 2009

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Abstract. Sarcoidosis is a systemic inflammatory disease characterised by appearance of granulomas. Precise etiology has not been elucidated. Osteopontin (Opn) is a Th1 cytokine whose levels have been found increased in granulomas and serum samples from patients with sarcoidosis. We investigated whether genetic variation in Osteopontin gene (OPN) gene contributes to susceptibility to sarcoidosis. Haplotype-block structure in the OPN gene region was investigated using data from HapMap project. Three representative SNPs have been selected from each block of SNPs in linkage disequilibrium (rs11730582-C/T, rs11728697-C/T and rs4754-C/T). Genotyping was performed using TaqMan SNP Genotyping Assays on a sample of 165 patients and 284 controls. Statistical analyses of association were performed using Chi-Square test and algorithms implemented in the haplo.stats and PHASE packages. Genotyping analysis revealed a significant difference in genotype frequencies at rs4754 polymorphism in groups of patients and controls under recessive genetic model (p = 0.036, OR = 1.99, 95%CI = 1.04-3.82), CC homozygotes being significantly over-represented in the patients group. However these results failed to reach significance after correction for multiple testing (p = 0.25). The frequencies of predicted haplotypes differed between patient and control groups, frequency of TTT haplotype was found to be significantly decreased in the group of patients with sarcoidosis (p = 0.014, OR = 0.40, 95%CI = 0.20-0.79). Our results suggest that variation in the OPN gene might be significantly associated with sarcoidosis and that the TTT haplotype in OPN may act as a protective factor in sarcoidosis.

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“…Moreover, an OPN promoter polymorphism at -66G and -443C recently has been identified to be associated with carotid artery intima media thickness, which reflects generalized atherosclerosis, and is predictive of future vascular events (43,44).…”

Section: Discussionmentioning

confidence: 99%

Osteopontin Is Associated with Increased Arterial Stiffness in Rheumatoid Arthritis

Bazzichi

Ghiadoni

Rossi

et al. 2009

Mol Med

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Rheumatoid arthritis (RA) patients are characterized by increased arterial stiffness, an independent predictor of cardiovascular risk. It has been suggested that osteopontin (OPN), a cytokine involved in RA pathogenesis, might have vascular effects. To study a possible relationship between OPN and arterial stiffness, aortic pulse wave velocity (PWV) was measured by tonometry in 69 patients (41 with RA, 28 with systemic sclerosis [SSc]) and 18 healthy controls. Plasma OPN levels, oxidative stress markers, and endothelin 1 (ET-1) were assessed. OPN levels were significantly (P < 0.05) higher in RA (median 9.93, range 4.36-47.80 ng/mL) than in SSc (4.3, 2.1-19.7 ng/mL) or controls (5.2, 4.1-9.4 ng/mL). In RA patients, log-OPN was related to log-C-reactive protein (log-CRP) (r = 0.30, P < 0.05), age (r = 0.38, P < 0.01), Health Assessment Questionnaire (HAQ) (r = 0.58, P < 0.0001), and inversely related to total cholesterol (r = -0.33, P < 0.05) and apolipoprotein A (apoA) (r = -0.58, P < 0.001), but not to oxidative stress markers and ET-1. PWV was similar in RA (median 8.1, range 4.7-16.4 m/s) and SSc (median 8.7, range 7.1-13.1 m/s), but significantly greater (P < 0.01) than controls (median 7.5, range 4.1-10.4 m/s). Aortic PWV was related to log-OPN (r = 0.40, P < 0.01) only in RA patients. It also was related to age (r = 0.34, P < 0.05), mean blood pressure (r = 0.44, P < 0.001), and HAQ (r = 0.48, P < 0.001). In multiple regression analysis (r 2 = 0.36), including confounders, log-OPN remained a significant predictor (P < 0.05) of PWV in RA. Elevated plasma OPN levels are associated with increased arterial stiffness in RA patients, suggesting that this protein might represent a bridge protein between inflammation and the consequent joint damage and cardiovascular risk in RA patients.

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Osteopontin Promoter Polymorphism Is Associated With Increased Carotid Intima-Media Thickness

Abstract: Background-Osteopontin (OPN)-transgenic mice exhibit increased carotid artery intima-media thickness (CIMT), smooth muscle cell proliferation, and atheroma formation.

Cited by 25 publications

References 53 publications

Association between osteopontin promoter variants and diastolic dysfunction in hypertensive heart in the Japanese population

Association between osteopontin promoter variants and diastolic dysfunction in hypertensive heart in the Japanese population

Genetic Variation in Osteopontin Gene Is Associated with Susceptibility to Sarcoidosis in Slovenian Population

Osteopontin Is Associated with Increased Arterial Stiffness in Rheumatoid Arthritis

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