AIMS To investigate the influence of ABCB1 (1236-2677-3435) polymorphisms on nortriptyline pharmacokinetics and nortriptyline-induced postural hypotension in healthy volunteers.
Our results suggest that homozygosity for 3435T alleles of ABCB1 is a risk factor for occurrence of nortriptyline-induced postural hypotension (OR = 1.37, P = 0.042, 95% CI 1.01-1.86).
We performed autonomic evaluations in 4 patients with lifelong orthostatic hypotension in whom <i>CYB561</i> mutations were determined by genomic sequencing.
This study is the first to implicate cytochrome b561 in disease by showing that pathogenic mutations in <i>CYB561</i> cause an as yet unknown disease in neurotransmitter metabolism causing orthostatic hypotension.
After analysis by sex and adjustment for conventional risk factors, the β1 -AR Gly389 homozygote conferred about a 3-fold risk of OH and independently predicted a 6.5 mm Hg greater orthostatic SBP decrease (GG -8.9±13 mm Hg vs CC+CG -2.4±12 mm Hg, P<.001) only in female hypertensive patients.
After analysis by sex and adjustment for conventional risk factors, the β1 -AR Gly389 homozygote conferred about a 3-fold risk of OH and independently predicted a 6.5 mm Hg greater orthostatic SBP decrease (GG -8.9±13 mm Hg vs CC+CG -2.4±12 mm Hg, P<.001) only in female hypertensive patients.
After analysis by sex and adjustment for conventional risk factors, the β1 -AR Gly389 homozygote conferred about a 3-fold risk of OH and independently predicted a 6.5 mm Hg greater orthostatic SBP decrease (GG -8.9±13 mm Hg vs CC+CG -2.4±12 mm Hg, P<.001) only in female hypertensive patients.
There were no significant associations between the maximum change in SBP, the prevalence of orthostatic hypotension and gene polymorphisms of angiotensin-converting enzyme I/D, angiotensinogen M235T and angiotensin II type 1 receptor A1166C.
Polymorphisms of genes encoding components of the sympathetic nervous system but not the renin-angiotensin system as risk factors for orthostatic hypotension.
A transthyretin (TTR) mutation is described in a 44 year old French woman from Caen who presented at the age of 40 with neuropathy in all four extremities, diarrhoea, and orthostatic hypotension.
To test this hypothesis, we fine-mapped the NEDD4L region in 2 families with orthostatic hypotension, which we previously reported to be linked to human chromosome 18q21 but failed to implicate NEDD4L in these families.
Polymorphisms of genes encoding components of the sympathetic nervous system but not the renin-angiotensin system as risk factors for orthostatic hypotension.
Polymorphisms of genes encoding components of the sympathetic nervous system but not the renin-angiotensin system as risk factors for orthostatic hypotension.
Polymorphisms of genes encoding components of the sympathetic nervous system but not the renin-angiotensin system as risk factors for orthostatic hypotension.
Other associations observed were only nominally significant after adjustments: NOS1rs2682826 A allele and excessive daytime sleepiness and sleep attacks (OR = 1.75; 95%CI = 1.00-3.06, p = 0.048), SOD2 rs4880 T allele and nausea/vomiting (OR = 0.49, 95%CI = 0.25-0.94; p = 0.031), IL1β rs1143623 C allele and orthostatic hypotension (OR = 0.57, 95%CI = 0.32-1.00, p = 0.050), and NOS1rs2682826 A allele and impulse control disorders (OR = 2.59; 95%CI = 1.09-6.19; p = 0.032).
We found Bonferroni adjusted (P < 0.0016) significant evidence for association between OH and the EBF1 locus (rs11953630, per-minor-allele odds ratio, 95% confidence interval: 0.90, 0.85-0.96; P = 0.001), and nominal evidence (P < 0.05) for CYP17A1 (rs11191548: 0.85, 0.75-0.95; P = 0.005), and NPR3-C5orf23 (rs1173771: 0.92, 0.87-0.98; P= 0.009) loci.
Other associations observed were only nominally significant after adjustments: NOS1 rs2682826 A allele and excessive daytime sleepiness and sleep attacks (OR = 1.75; 95%CI = 1.00-3.06, p = 0.048), SOD2rs4880 T allele and nausea/vomiting (OR = 0.49, 95%CI = 0.25-0.94; p = 0.031), IL1β rs1143623 C allele and orthostatic hypotension (OR = 0.57, 95%CI = 0.32-1.00, p = 0.050), and NOS1 rs2682826 A allele and impulse control disorders (OR = 2.59; 95%CI = 1.09-6.19; p = 0.032).
We found Bonferroni adjusted (P < 0.0016) significant evidence for association between OH and the EBF1 locus (rs11953630, per-minor-allele odds ratio, 95% confidence interval: 0.90, 0.85-0.96; P = 0.001), and nominal evidence (P < 0.05) for CYP17A1 (rs11191548: 0.85, 0.75-0.95; P = 0.005), and NPR3-C5orf23 (rs1173771: 0.92, 0.87-0.98; P= 0.009) loci.