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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 1, January/February 2016
24
AFRICA
Various studies have shown cardiovascular risk factors
such as type 2 diabetes mellitus,
9,10
insulin resistance,
11
and
hypertension
12
were associated with the risk allele A for
FTO
rs9939609 and the risk allele C for
MC4R
rs17782313, regardless
of BMI.
9,10
But in Marcadenti and colleagues’ study, common
genetic variants of
FTO
rs9939609 had positive associations
with BMI and neck circumference and
MC4R
rs17782313 in
women, but a negative association with diastolic and mean blood
pressure in hypertensive men in southern Brazil.
13
However, these
associations need to be confirmed by further replication studies,
particularly in other ethnic populations. Brazilians and Chinese
are different in their environmental risk factors, medical profiles,
body composition and genetic backgrounds.
This study has some limitations that should be taken into
account when interpreting the results. The analysis of genotype
by gender was exploratory and it was underpowered to detect
small differences. Therefore, some associations that achieved
statistical significance in the overall analysis remained only as a
trend towards that association. The association of gene variants
with anthropometric indices should be confirmed in further
studies with statistical power to carry out analysis by gender.
Conclusion
We found that the
FTO
and
MC4R
genes were risk factors for
nocturnal hypertension in this Chinese Han population, and
their combined effects played an important role in nocturnal
hypertension. However, even if a gene were considered associated
with hypertension in certain populations, to expand the
conclusion to all human populations is arbitrary. Furthermore,
in the investigation of hypertension, obesity or diabetes, not
only genetic factors but other factors, such as environment or
geographic location could play a role. All these factors could
have different effects on obesity or diabetes and they could
impact on each other. Therefore whether or how a single gene
could be associated with nocturnal hypertension is a complicated
question. To decipher this, one would need long-term studies
with numerous patients.
FTO
is a new gene reported by Yi-Cheng
and co-workers in 2007,
2
and thus far we have not answered all
the questions since there has been minimal research on this gene
among the different nations. We need more studies, since from
a population perspective, only the combined effect of the most
potent genetic variants should be considered.
This study was funded by the Hubei Provincial Bureau of Health Science
Foundation for Young Scholars (grant QJX2008-29).
References
1.
Zacho J, Timpson, Nordestgaard BG. Does greater adiposity increase
blood pressure and hypertension risk? Mendelian randomization using
the
FTO
/
MC4R
genotype.
Hypertension
2009;
54
: 84–131.
2.
Yi-Cheng C, Pi-Hua L, Wei-Jei L. Common variation in the fat mass
and obesity-associated (
FTO
) gene confers risk of obesity and modu-
lates BMI in the Chinese population.
Diabetes
2008; 57(8): 2245–2252.
3.
Villalobos-Comparán MM, Flores-Dorantes TM
,
Villarreal-Molina
T. The
FTO
gene is associated with adulthood obesity in the Mexican
population.
Obesity
2008;
16
: 2296–2301.
4.
Seong WC, Sun MC, Kil SK. Replication of genetic effects of
FTO
polymorphisms on BMI in a Korean population.
Obesity
2008;
16
:
2187–2189.
5.
Frayling TM, Timpson NJ, Weedon MN. A common variant in the
FTO
gene is associated with body mass index and predisposes to childhood
and adult obesity.
Science
2007;
316
: 889–894.
6.
Wijkman M, Länne T, Engvall J, Nystrom. Masked nocturnal hyperten-
sion – a novel marker of risk in type 2 diabetes.
Diabetologia
2009;
52
:
1258–1264.
7.
Struan FA, Grant JP. Bradfield I, Haitao Z. Investigation of the locus
near
MC4R
with childhood obesity in Americans of European and
African ancestry.
Obesity
(Silver Spring) 2009;
17
(7): 1461–1465.
8.
Cauchi S, Stutzmann F, Cavalcanti-Proença C. Combined effects of
MC4R
and
FTO
common genetic variants on obesity in European
general populations.
J Mol Med
2009;
87
: 537–546.
9.
Li H, Kilpeläinen TO, Liu C. Association of genetic variation in
FTO
with risk of obesity and type 2 diabetes with data from 96,551 East and
South Asians.
Diabetologia
2012;
12
: 981–995.
10. Qi L, Kraft P, Hunter DJ. The common obesity variant near
MC4R
gene is associated with higher intakes of total energy and dietary fat,
weight change and diabetes risk in women.
Hum Mol Genet
2008;
12
:
3502–3508.
11. Tschritter O, Haupt A, Preissl H. An obesity risk SNP (rs17782313) near
the
MC4R
gene is associated with cerebrocortical insulin resistance in
humans.
J Obes
2011;
12
: 283–293.
12. Pausova Z, Syme C, Abrahamowicz M. A common variant of the
FTO
gene is associated with not only increased adiposity but also elevated
blood pressure in French Canadians.
Circ Cardiovasc Genet
2009;
12
:
260–269.
13. Marcadenti A, Fuchs FD, Matte U. Effects of
FTO
RS9939906 and
MC4R
RS17782313 on obesity, type 2 diabetes mellitus and blood
pressure in patients with hypertension.
Cardiovascr Diabetol
2013;
12
:
1186–2840.
14. Hubacek JA, Pitha J, Adamkova V. A common variant in the
FTO
gene is associated with body mass index in males and postmenopausal
females but not in premenopausal females.
Clin Chem Lab Med
2009;
47
: 387–390.
15. Ernsberger P, Haskew P. Health implications of obesity: an alternative
view.
J Obes Weight Regul
1987;
6
: 55–137.
16. Gregg EW, Cheng YJ, Cadwell BL. Secular trends in cardiovascular
disease risk factors according to body mass index in US adults.
J Am
Med Assoc
2005;
293
: 1868–1874.
17. Troiano RP, Frongillo EA Jr, Sobal J. The relationship between body
weight and mortality: a quantitative analysis of combined information
from existing studies.
Int J Obes Relat Metab Disord
1996;
20
: 63–75.
18. Sanchez-Pulido L, Andrade-Navarro MA. The
FTO
(fat mass and
obesity associated) gene codes for a novel member of the non-heme
dioxygenase superfamily.
BMC Biochem
2007;
8
: 8–23.