Glycoprotein gene flags up heart disease

The glycosylphosphotidylinositol (GPI)-anchored membrane glycoprotein CD14 gene significantly predicts cardiovascular mortality in adults aged 65 years or over, research shows.

Alex Reiner (University of Washington, Seattle, USA) et al explain in Arterioclerosis, Thrombosis, and Vascular Biology that CD14 is constitutively expressed on monocytes or macrophages and neutrophils. In current study, genomewide association analysis showed that there are two significant soluble CD14 (sCD14)-associated loci: the CD14 structural locus on chromosome 5q21, and a novel missense variant of PIGC, which encodes an enzyme required for the first step in GPI anchor biosynthesis.

Reiner and team found that sCD14 was positively correlated with baseline smoking, Type 2 diabetes, fasting glucose, and hypertension, and was negatively correlated with body mass index in a cohort of over 5000 European-American and Black adults. All participants were aged 65 years over and were characterized at baseline for atherosclerotic risk factors and subclinical cardiovascular disease (CVD). The mean sCD14 level at baseline was 1641 ng/mL.

After adjusting for baseline coronary heart disease and CVD risk factors, sCD14 was strongly and independently associated with other inflammatory and acute-phase proteins, including C-reactive protein, interleukin-6, and fibrinogen, as well as with increased internal carotid artery wall thickness and decreased ankle-brachial index.

Among the 5462 European-American and Black participants who had sCD14 measured at baseline, 820 incident myocardial infarctions, 1547 incident coronary heart disease events, 945 incident strokes, and 3820 deaths occurred over a 20-year follow-up period. Of the deaths, 1519 were attributed to CVD causes and 2290 to non-CVD causes.

Multivariate analysis revealed a graded, linear increase in CVD mortality risk with each successive sCD14 quintile. Compared with the bottom quintile, the hazard ratios for the second, third, fourth, and fifth quintiles were 1.00, 1.02, 1.12, and 1.27, respectively. The hazard ratios comparing the top with bottom quintiles for CVD and non-CVD death were 1.26 and 1.32, respectively.

"Whether higher levels of sCD14 or other inflammatory mediators are directly causal, or indicative of chronic, low level infection and other immune alterations in older adults, or simply reflect worsening subclinical and clinical disease, is difficult to distinguish," write the authors.

"Nonetheless, sCD14 may have potential clinical utility as a marker of aging, disease risk, or disease progression in older adults."

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