3 CHAPTER 3 56 remarkable sex differences (Table S1). L-Threonine additionally showed higher correlation in females and SDMA showed a lower concentration in females compared to males. Plasma/CSF ratios metabolite correlations Next, we tested whether metabolite ratios in plasma correlated with the same ratio in CSF. Correlations between all possible ratios were calculated based on their R2 (Figure 2, Table S2). As expected, metabolites that already had strong single-correlations (i.e. homocitrulline, S-methylcysteine, methionine sulfone, L-alpha-aminobutyric acid, and L-threonine), also showed strong correlation for most ratios with other amines. Additionally, several other metabolite pairs showed high correlation. For example, for the single L-Valine correlation the R2 = .11 and for the single L-Phenylalanine correlation the R2 was .01, but the plasma ratio of L-Valine/L-Phenylalanine had a higher correlation with the CSF ratio of L-Valine/L-Phenylalanine This means that 67% of the variance in y (the ratio between L-Valine/L-Phenylalanine in CSF) is explained by x (the ratio between L-Valine/L-Phenylalanine in plasma) (Figure 3A-C). Sex differences in the correlations were minor for any the ratio pairs (Table S2, Figure S2A, B). Primarily, the amino acids showed a high correlation in their ratios. The improvement in R2 ratio correlation (R2 gain) compared to single-correlation is illustrated in Figure 4. The ratio correlations were significantly higher than the related single-metabolite correlations for 308 of 741 (41.5%) amine combinations, i.e. after multiple testing correction (FDR < .05) (Figure 4, Table S3). As a control, the correlations between the product of two amines were tested, but did not show clear significance (data not shown). Table 1 Clinical characteristics of healthy controls Healthy controls Number of participants 95 Subject characteristics Females (n, (%)) 56 (58.9) Years of age (± SD‡) 38.8 (± 14.5) BMI† (± SD‡) 23.7 (± 2.8) Smoking (n, (%)) 20 (21.1) Overnight fasting Fasting time in h (± SD‡) 11.6 (± 2.4) Sampling characteristics Opening pressure in mmH2O (± SD‡) 19.1 (± 4.4) CSF characteristics Erythrocytes count/3µL (± SD‡) 154 (± 934) Leukocytes count/3µL (± SD‡) 6 (± 6) Protein concentration in g/L (± SD‡) .35 (± .13) Glucose in mmol/L (± SD‡) 3.2 (± .3) † BMI = body mass index;‡ SD = standard deviation
RkJQdWJsaXNoZXIy MTk4NDMw