engleski

PLASMA N-GLYCOME AS INCIDENCE HYPERTENSION PREDICTOR

Objective: N-glycosylation, one of the most complex co- and post-translational modifications, is a highly regulated process influenced by many diseases. There is evidence that N-glycosylation could be a marker of hypertension. The aim of this study was to determine if plasma N-glycome is a predictor of incident hypertension (HTN). Design and method: We selected 271 unrelated cases with incident hypertension and 271 controls matched for age, BMI and follow-up time from the TwinsUK cohort (mean follow-up time was 8.5 years). Longitudinal plasma N-glycome (39 directly measured traits) was measured by ultra- performance liquid chromatography (HILIC-UPLC). Logistic regression with elastic net penalty (a=1 and l=10e-2) and 10-fold cross validation was implemented on this subset fitting two models: null, with baseline age, BMI and follow-up time, and glyco, with null + baseline plasma N-glycans as predictors. Models were evaluated by comparing their area under the curves using bootstrap test. Most important glycans contributing to the prediction of incident HTN in elastic net were further assessed by Cox survival analysis to estimate their effect on the risk of incident HTN. Cox models were fi tted using the whole dataset, with baseline BMI and age as covariates and Family ID as random effect. Results: Glyco model (AUC=0.628, 95%CI=0.582-0.675) was significantly better in prediction of incident HTN in contrast to null model (AUC=0.524, 95%CI=0.475-0.570 ; p<0.001) explaining an extra 10%. The glyco model identifi ed 6 plasma glycans mostly contributing to the prediction. These include four high branched structures with two to four sialic acids (GP25, GP27, GP31, GP32) originating from a-1-acid glycoprotein, one structure with two branches and one sialic acid (GP15), and one glycan peak (GP2) without sialic acid, related to high mannose structure or structure ending with a bisecting N- acetylglucosamine residue. Cox survival analysis showed that only GP32 significantly increased risk (log(HR)=0.253, 95%CI=0.075-0.432 ; p=0.006) of incident hypertension. Conclusions: Baseline plasma N-glycome is associated with incident hypertension in our cohort of adult female subjects. N-glycome of a- 1-acid glycoprotein appears to contribute the most to hypertension risk and merits further validation studies in independent cohorts.

plasma ; glycan ; incident hypertension

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