Blood Pressure Response to Sodium in the Diet
| Status: | Completed |
|---|---|
| Conditions: | High Blood Pressure (Hypertension) |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 4/2/2016 |
| Start Date: | January 2005 |
| End Date: | July 2014 |
D1 and AT1 Receptor Interaction in Human Hypertension: Sodium Sensitivity of Blood Pressure
Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) of the
sodium-bicarbonate co-transporter gene (SLC4A5) are associated with hypertension. We tested
the hypothesis that SNPs in SLC4A5 are associated with salt sensitivity of blood pressure in
185 whites consuming an isocaloric constant diet with a randomized order of 7 days of low
sodium (Na+) and 7 days of high Na+ intake. Salt sensitivity was defined as a ≥7-mm Hg
increase in mean arterial pressure during a randomized transition between low and high Na+
diet.
A total of 35 polymorphisms in 17 candidate genes were assayed, 25 of which were tested for
association. Association analyses with salt sensitivity revealed 3 variants that associated
with salt sensitivity. Of these, 2 SNPs in SLC4A5 (rs7571842 and rs10177833) demonstrated
highly significant results and large effects sizes, using logistic regression. These 2 SNPs
had P values of 1.0×10−4 and 3.1×10−4 with odds ratios of 0.221 and 0.221 in unadjusted
regression models, respectively, with the G allele at both sites conferring protection.
These SNPs remained significant after adjusting for body mass index and age (P=8.9×10−5 and
2.6×10−4 and odds ratios 0.210 and 0.286, respectively). Furthermore, the association of
these SNPs with salt sensitivity was replicated in a second hypertensive population.
Meta-analysis demonstrated significant associations of both SNPs with salt sensitivity
(rs7571842 [P=1.2×10−5]; rs1017783 [P=1.1×10−4]).
In conclusion, SLC4A5 variants are strongly associated with salt sensitivity of blood
pressure in 2 separate white populations.
sodium-bicarbonate co-transporter gene (SLC4A5) are associated with hypertension. We tested
the hypothesis that SNPs in SLC4A5 are associated with salt sensitivity of blood pressure in
185 whites consuming an isocaloric constant diet with a randomized order of 7 days of low
sodium (Na+) and 7 days of high Na+ intake. Salt sensitivity was defined as a ≥7-mm Hg
increase in mean arterial pressure during a randomized transition between low and high Na+
diet.
A total of 35 polymorphisms in 17 candidate genes were assayed, 25 of which were tested for
association. Association analyses with salt sensitivity revealed 3 variants that associated
with salt sensitivity. Of these, 2 SNPs in SLC4A5 (rs7571842 and rs10177833) demonstrated
highly significant results and large effects sizes, using logistic regression. These 2 SNPs
had P values of 1.0×10−4 and 3.1×10−4 with odds ratios of 0.221 and 0.221 in unadjusted
regression models, respectively, with the G allele at both sites conferring protection.
These SNPs remained significant after adjusting for body mass index and age (P=8.9×10−5 and
2.6×10−4 and odds ratios 0.210 and 0.286, respectively). Furthermore, the association of
these SNPs with salt sensitivity was replicated in a second hypertensive population.
Meta-analysis demonstrated significant associations of both SNPs with salt sensitivity
(rs7571842 [P=1.2×10−5]; rs1017783 [P=1.1×10−4]).
In conclusion, SLC4A5 variants are strongly associated with salt sensitivity of blood
pressure in 2 separate white populations.
Subjects are placed on an isocaloric diet, one week with high sodium(300mEq) and one week
with low sodium(10mEq), in randomized order. Twenty-four hour urine sodium and urine
creatinine levels verify diet compliance. Blood pressure measurements are recorded during
each diet week by automated blood pressure monitoring system. Each blood pressure is taken
in the right arm 3 times while the subject is sitting quietly for 45 minutes .
with low sodium(10mEq), in randomized order. Twenty-four hour urine sodium and urine
creatinine levels verify diet compliance. Blood pressure measurements are recorded during
each diet week by automated blood pressure monitoring system. Each blood pressure is taken
in the right arm 3 times while the subject is sitting quietly for 45 minutes .
Inclusion Criteria:
- Ages 18-70 (inclusive)
- Sex Male and female
- Race Caucasian and African-American/black
- BMI 18-29
Exclusion Criteria:
- malignant hypertension
- blood pressure > 180/114 mmHg
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