Serum Dopamine Beta Hydroxylase (DβH) enzyme activity changes within individual women according to stage of pregnancy: Evidence that regulation of expression of DβH differs during pregnancy in women carrying different genotypes at rs1611115. Öffentlichkeit
Perdomo, Dannie Lynn (2012)
Published
Abstract
Abstract
Serum Dopamine Beta Hydroxylase (DβH) enzyme activity changes within individual women according to stage of pregnancy: Evidence that regulation of expression of DβH differs during pregnancy in women carrying different genotypes at rs1611115.
By Dannie L. Perdomo
Dopamine Beta Hydroxylase (DβH) is a vesicular enzyme that plays a crucial role in the catecholaminergic pathway by converting dopamine into norepinephrine. DβH activity levels are easily assayed in serum due to the release of DbH along with NE from noradrenergic neurons as well as from chromaffin granules of the adrenal medulla. Early efforts to use serum DbH as an index of sympathetic activity rapidly led to the finding that serum DbH activity is regulated largely by genetic inheritance. Subsequent work has demonstrated conclusively that DBH is the major quantitative trait locus regulating serum DbH.
Dbh -/- mouse embryos die in utero and mothers of persons born with the rare Mendelian disorder of DβH deficiency report high rates of miscarriage (Senard and Rouet 2006). In the current study, we examine serum DbH activity across pregnancy in women seeking care for mental illness. We hypothesized that: (1) serum DβH activity will change over the course of pregnancy; (2) those changes will be affected by the main effect SNP, rs1611115, a well-documented functional SNP at DBH that accounts or ~50% of the variance in serum DbH activity. Serum samples were drawn during the pre-conception period, the 1st, 2nd, and 3rd trimester, and the early (first 8 weeks) and late (9- 25 weeks) post partum period. Serum DβH activity decreases across each trimester in pregnancy with its lowest point in the 3rd Trimester (3) (t=-10.95, p<.0001; Figure 1). It then begins to recover after delivery to Preconception (0) levels (t=.94; p=NS). Consistent with previous reports, the CC genotype associated with higher serum DβH activity than the CT or TT genotypes (F=51.18; p<.0001). There is a significant interaction between genotype at 1611115 and time in pregnancy (F=3.39, p<0.008), suggesting that women who carry the TT (low-serum DbH-associated) genotype regulate expression of the DBH gene differently across pregnancy than those carrying at least one C allele.
Table of Contents
Table of Contents
Chapter 1 Introduction to Dopamine Beta Hydroxylase (DBH)...1
Chapter 2: Genotype-controlled analysis of serum dopamine
β-hydroxylase (DβH) activity during pregnancy and the
post-partum period in women with psychiatric disorders
A. Introduction...8
B. Methods
a. Biological samples and Human
Subjects...11
b. DβH Enzyme Assay...12
c. Genotyping...12
d. Statistical analysis...13
C. Results...14
D. Discussion...15
Chapter 3: Supplemental Methods...25
A. Additional Notes on Methods...25
B. Statistical tests...26
References
For DβH Review...28
For DβH & Pregnancy Paper...38
I. TABLE OF IMAGES
A. DβH Review
FIGURE 1: Dopamine Beta Hydroxylase (DβH)...6
B. DβH & Pregnancy Paper
Supplementary Table 1: Hardy-Weinberg
Equilibrium...18
TABLE 1: Defined Time Periods of Pregnancy...18
TABLE 2: Descriptive statistics including age, parity, and BDI for
each mother...19
Supplementary Table 2: Medication Regime for the Moms...19
TABLE 3: Descriptive Statistics of DβH Activity for the all
samples...20
Supplementary Figure 1 a, Q-Q Plot b. Histogram...21
TABLE 4: Descriptive Statistics...23
FIGURE 1: Box-plots of SQRT DBH Activity across
Pregnancy-...22
FIGURE 2: Box-plots of SQRT DBH Activity Relative to
Genotype...23
FIGURE 3: Genotype Dependent Serum DβH Activity across
Pregnancy...24
C. Chapter 3: Supplemental Methods
FIGURE 1: HPLC-ECD...27
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Serum Dopamine Beta Hydroxylase (DβH) enzyme activity changes within individual women according to stage of pregnancy: Evidence that regulation of expression of DβH differs during pregnancy in women carrying different genotypes at rs1611115. () | 2018-08-28 14:30:08 -0400 |
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