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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 1, January/February 2016
AFRICA
23
Effects of
FTO
and
MC4R
on nocturnal hypertension
The effects of
FTO
rs9939609 on nocturnal hypertension are
shown in Table 3. Interestingly, the distribution of the genotypes
and the two alleles were significantly different between the
nocturnal hypertension group of patients and the controls (
χ
2
=
18.54 and
χ
2
=
19.39, respectively;
p
<
0.05). The A allele
frequency and the AA frequencies were significantly higher in
the patients than in the controls, as seen in Table 3. The increase
in odds ratio of the A allele for the nocturnal blood pressure
group was 1.37 (95% CI: 1.19–1.58). The genotypic odds ratio for
elevated nocturnal blood pressure was 1.82 (95% CI: 1.38–2.41)
for the AA genotype, and 1.39 (95% CI: 1.10–1.75) for the AT
genotype.
The effects of
MC4R
rs17782313 on nocturnal hypertension
is shown in Table 3. The distribution of the genotype and the
two alleles were also significantly different between the nocturnal
hypertension group and the controls (
χ
2
=
15.21 and
χ
2
=
12.88,
respectively;
p
<
0.05). The C allele frequency and CC frequencies
were significantly higher in the patients than in the controls, as
seen in Table 3. The increase in odds ratio of the C allele for the
nocturnal hypertension group was 1.69 (95% CI: 1.31–3.32). The
genotypic odds ratio for nocturnal hypertension was 1.54 (95%
CI: 1.39–4.13) for the CC genotype, and 1.28 (95% CI: 1.60–2.88)
for the CT genotype.
The combined effects of
FTO
rs9939609 and
MC4R
rs17782313
on nocturnal hypertension is shown in Fig. 1. In this study, we
observed that the nocturnal blood pressure of the participants
simultaneously carrying the A and C alleles was significantly
higher than the BP of those carrying neither
FTO
nor
MC4R
risk
allele (
χ
2
=
28.79,
p
<
0.05), and the BP of the controls carrying
only the A or C alleles (
χ
2
=
25.74,
p
<
0.05) (Fig. 1).
Discussion
Obesity and BMI are known to be associated with hypertension.
Increases inBMI lead to an increase in the burdenof hypertension.
However, Ernsberger and Haskew found increasing prevalence
of obesity as well as average BMI levels were accompanied by
significant decreases in blood pressure level and prevalence of
hypertension.
15
This has led to questions about the nature of the
association between obesity and hypertension.
Gregg
et al
. found both nocturnal and daytime systolic blood
pressure predicted cardiovascular events independently of clinic
systolic BP levels.
16
In the general population, Ernsberger and
Haskew found nocturnal BP was a better predictor of fatal
cardiovascular events than daytime BP.
15
Troiano and co-workers
found the risk for cardiovascular death increased more steeply
with increasing nocturnal BP levels than with increasing daytime
BP levels.
17
In our study, the analysis demonstrated a significant
association of the
FTO
and
MC4R
genes with nocturnal
blood pressure in the Chinese Han population (
p
<
0.05). The
combined effects of
FTO
and
MC4R
played an important role
in nocturnal blood pressure levels in this population. Nocturnal
blood pressure levels of the participants carrying three or four
risk alleles were higher than those with neither
FTO
nor
MC4R
risk allele (
p
=
0.008), those with one risk allele (
p
=
0.025), and
those with two risk alleles (
p
=
0.041). The mechanism may
be related to the
FTO
protein, which is a key link between the
central nervous system and energy balance.
The
FTO
gene function is unknown but based on its
predicted structure, the
FTO
gene encodes for a non-haeme
(FeII) dioxygenase with a potential role in adaptation to
hypoxia, lipolysis or DNA methylation.
17,18
The
FTO
protein
is expressed in almost all tissues; at the cellular level it has a
nuclear localisation.
17
The molecular mechanisms involved in the
pathogenesis of obesity as well as the role of
FTO
gene in other
complex disorders are unknown.
Table 3.
FTO
rs9939609 and
MC4R
rs17782313 distributions in nocturnal hypertension and control groups
Groups
n
FTO
rs9939609
MC4R
rs17782313
Genotypes,
n
(frequency)
Alleles,
n
(frequency)
Genotypes,
n
(frequency)
Alleles,
n
(frequency)
AA
AT
TT
A
T
CC
CT
TT
C
T
Nocturnal hypertension 583 140 (24.0) 281 (48.2) 162 (27.8) 561 (48.1) 605 (51.9)
82 (14.1)
252 (43.2) 249 (42.7) 416 (35.7) 750 (64.3)
Controls
1200 205 (17.1) 545 (45.4) 450 (47.5) 955 (39.8) 1445 (60.2) 116 (9.7)
476 (39.7) 608 (50.6) 708 (29.5) 1692 (70.5)
Data are means (SD) for genotypic classes on unrelated individuals.
FTO
rs9939309: with Pearson
χ
2
test, comparison of genotypes: nocturnal hypertension vs controls,
χ
2
=
18.54,
p
<
0.05;
comparison of alleles: nocturnal hypertension vs controls,
χ
2
=
19.39,
p
<
0.05;
MC4R
rs17782313: with Pearson
χ
2
test, comparison of genotypes: nocturnal hypertension vs controls,
χ
2
=
15.21,
p
<
0.05;
comparison of alleles: nocturnal hypertension vs controls,
χ
2
=
12.88,
p
<
0.05.
155
150
145
140
135
130
125
120
100
90
80
70
60
50
40
30
20
10
0
0 (25%) 1 (38%) 2 (31%) 3–4 (6%)
Number of risk alleles (% of samples)
SBP (mmHg)
DBP (mmHg)
SBP (left)
DBP (right)
Fig. 1.
Nocturnal blood pressure according to risk allele at
rs9930609 and rs17782313. Nocturnal hypertension
of participants carrying neither
FTO
nor
MC4R
risk
allele (25% of the population) was 130.9
±
4.9/71.4
±
3.7 mmHg, those carrying one risk allele (38% of the
population) was 135.9
±
5.5/75.0
±
3.8 mmHg, those
carrying two risk alleles (31% of the population) was
142.2
±
4.7/80.6
±
2.3 mmHg and those carrying there
or four risk alleles (6% of the population) was 151.3
±
6.4/88.5
±
5.1 mmHg.