Abstract 19305: Higher Levels of Beta-2 Microglobulin Predict Incident Hypertension
Background and significance: Beta-2-microglobulin (β2M) is a subunit of the histocompatibility class I (MHC I) molecule and a biomarker of renal dysfunction. Prior studies have shown associations of serum β2M with cardiovascular diseases (CVD). We tested for genetic effects on serum β2M in 6769 Framingham Heart Study (FHS) participants and observed significant genome-wide associations (GWAS) with variants at the HLA-C and SH2B3 loci. β2M-related genetic variants at the SH2B3 loci were also associated with blood pressure. Accordingly, we characterized the association of serum β2M levels with new-onset hypertension.
Methods and results: Study population was composed of FHS Offspring and Third Generation cohort participants with baseline B2M and blood pressure (BP) measured in the subsequent examination cycle 6 years later. After excluding participants with hypertension (systolic BP ≥140 mmHg, diastolic BP ≥90mmHg, or medication treatment for hypertension, n=1519) or CVD (n=270) or cancer (n=240), 3689 participants (mean age 44; 57% women) were included in the analysis. A total of 681 (18%) participants developed new-onset hypertension. Logistic regression adjusting for age, sex, body-mass-index, and diabetes, revealed that higher β2M levels at baseline predicted new-onset hypertension; a 1 standard deviation higher β2M level was associated with a 14% higher risk of developing hypertension (odds ratio 1.14, 95% CI 1.002-1.297, p=0.047). The relation of B2M to incident hypertension remained marginally significant (odds ratio 1.13, 95%C.I. 1.0, 1.299, p=0.05) after excluding participants with renal dysfunction.
Conclusion: Our finding that higher serum β2M levels predict risk of new-onset hypertension, in conjunction with GWAS results for β2M, suggest a causal role of β2M in hypertension. Additional mechanistic studies are warranted.
- Cardiovascular disease
- Diabetes Mellitus
- Genome-wide association studies (GWAS)
- Renal function
Author Disclosures: S. Hwang: None. G. Chen: None. C. Yao: None. C. Liu: None. C. Song: None. T. Huan: None. M. Mendelson: None. A. Lyass: None. P. Courchesne: None. A.D. Johnson: None. D. Levy: None.
- © 2016 by American Heart Association, Inc.