Vol.2, No.3, 268-271 (2010)
Copyright © 2010 SciRes Openly accessible at http://www.scirp.org/journal/HEALTH/
Does FMF have a property to protect children from
Faysal Gök1, İsmail Dursun2, İbrahim Gökçe2
1Department of Pediatric Nephrology and Rheumatology, Gülhane Military Medical Academy, School of Medicine, Ankara, Turkey;
2Department of Pediatric Nephrology and Rheumatology, Gülhane Military Medical Academy, School of Medicine, Ankara, Turkey;
drdursun@hotmail.com, gokcemd@yahoo.com
Received 20 November 2009; revised 11 January 2010; accepted 15 January 2010.
Objectives: This study investigates the preva-
lence of obesity in children with familial Medi-
terranean fever (FMF). Material and Methods: We
retrospectively reviewed the medical records of
70 patients with FMF whose cases had been fol-
lowed in our Pediatric Nephrology and Rheuma-
tology Unit. The height and weight measure-
ments of children with FMF were obtained and
body mass index was calculated. Results: The
mean body mass index was 16.7± 2.4 in the boys,
and 17.4±2.9 in the girls. Nine of the children
(five boys, four girls) were found to be over-
weight, a rate of 12.8% in FMF patients. Obesity
was not detected in FMF patients. Conclusions:
We think that there are some unligteening mo-
lecular mechanisms that prevent obesity in FMF
patients. Due to the limited number of patients in
this study, further research involving more pa-
tients are needed.
Keywords: Familial Mediterranean Fever; Obesity;
Children; Adipocytokines
Familial Mediterranean fever (FMF), an autosomal re-
cessive disorder common in Mediterranean and Middle
Eastern populations, especially in Sephardic Jewish,
Armenian and Turkish populations, is characterized by
recurrent episodes of fever, abdominal pain, joint pain,
and less frequently, pleuritis, pericarditis and rash, de-
scribed as erysipelas-like erythema [1]. The prognosis of
this disease depends on the development of the amyloi-
dosis of AA type with prominent renal involvement [2].
The molecular mechanism of FMF is still not clear. The
gene causing FMF, known as MEFV (MEditerranean
FeVer), has been mapped on the short arm of chromo-
some 16 [3]. It has been shown that substantial subclinical
inflammation occurs widely and over prolonged periods
in patients with FMF, indicating that the relatively in-
frequent clinically overt attacks represent the tip of the
iceberg in this disorder [4].
Obesity is characterized by a state of chronic low-grade
inflammation [5]. The basis for this view is that increased
circulating levels of several markers of inflammation,
both pro-inflammatory cytokines and acute-phase pro-
teins, are elevated in the obese; these markers include
IL-6, the TNFa system, C-reactive protein (CRP) and
haptoglobin [6]. Nevertheless, it is increasingly evident
that the inflammatory state may be causal in the devel-
opment of insulin resistance and the other disorders as-
sociated with obesity, such as hyperlipidaemia and
metabolic syndrome [5]. While the general assumption is
that inflammation is consequent to obesity, it has been
suggested that obesity is in fact a result of inflammatory
disease [6].
Although studies regarding the etiologic factors of
FMF and obesity have been reported, the eligible etiology
of neither FMF nor obesity is clear yet. The influence of
FMF on the growth parameter has been reported [7-9].
According to literature, the prevalence of both diseases is
high in the Turkish population [10,11]. Thus we aimed to
show the relationship between the diseases and the
prevalence of overweight and obesity in FMF patients.
We retrospectively reviewed the medical records of 70
patients with FMF whose cases had been followed up in
our Pediatric Nephrology and Rheumatology Unit. The
diagnosis of FMF had been made according to the diag-
nostic criteria and mutational analysis [12,13]. Only pa-
tients who had homozygosity and/or compound het-
erozygosity for MEFV mutations were included in this
study. Body height and weight were measured by trained
paediatric specialists. For the measurements, the patients
F. Gök et al. / HEALTH 2 (2010) 268-271
Copyright © 2010 SciRes Openly accessible at http://www.scirp.org/journal/HEALTH/
were dressed in light indoor clothing and bare feet or
stockings. The subjects were weighed to the nearest 0.1
kg with an electronic scale (SECA 762; Vogel & Hakle,
Hamburg, Germany) calibrated daily at the beginning of
each working day. Height was measured with a stadi-
ometer in the vertical position, erect, with parallel feet
and ankles, and with the shoulders and bottom touching
the wall. The height and weight data were used to calcu-
late the body mass index (BMI) (kg/m2) using the for-
mula: weight (kg) divided by height (m) squared. The
BMI normalized centile curves for Turkish children were
applied to define obesity and the values of 95 percent or
more were accepted as obesity [11].
All tests were performed using SPSS for Windows 15.0.
The parameters with normal distribution were expressed
as mean ± SD. Comparisons of means were performed
with an unpaired t-test. Comparisons of proportions were
performed with a Pearson-chi-squared test. A P value
<0.05 was accepted as statistically significant.
The study population consisted of 70 children with FMF
(34 boys, 36 girls). Table 1 shows the age distribution
and anthropometric parameters of the FMF patients. The
mean age of boys and girls was 8.9±3.5 (range 5-18
years) and 9.4±3.1 (range 5-16 years), respectively. The
mean of BMI was 16.7±2.4 in boys, 17.4±2.9 in girls.
Overweight was diagnosed in 9 (5 boys, 4 girls) and the
prevalence of overweight is 12.8% in FMF patients.
Obesity was not detected in FMF patients. The results of
genotype of the patients with FMF are shown in Table 2.
In this study we investigated the prevalence of obesity in
FMF patients. Obesity is a problem of public health and
its prevalence is increasing rapidly worldwide [14]. The
prevalence of obesity and overweight has been reported
9.7-12.8% and 11.6-25%, respectively, in Turkish chil-
dren [11,15-17]. Regarding the study group, the number
of obese children at least was expected to be seven, but
none were found; and the P value <0.05 was statistically
significant. The rate of overweight in the study group
was the same as in Turkish healthy children.
Shortened growth is a frequent complication in the
chronic inflammatory diseases of childhood [18]. Growth
in children with FMF has been evaluated in three previ-
ous studies [7-9]. Savgan et al. reported that children
with FMF have growth patterns no different from those
of their healthy peers. Zung et al. showed that colchi-
cine therapy has a positive effect on anthropometric
Table 1. Age distrubution and antropometric parameters of the
patients with FMF.
Variables FMF (boys)
FMF (girls)
Age (years) 8,9±3,5 9,4±3,1
BMI (kg/m2) 16,7±2,4 17,4±2,9
Overweight 5 4
Table 2. Major genotypes in FMF patients.
Mutations n (%)
M694V–M694V 28 (40)
M694V–V726A 13 (18.5)
M694V–M680I 11(15.7)
M694V–E148Q 7 (10)
M680I–M680I 3 (4.2)
V726A–E148Q 2 (2.8)
V726A–V726A 1 (1.4)
E148Q– E148Q 1 (1.4)
M694V/R761H 1 (1.4)
M680I/V726A 1 (1.4)
V726A/R761H 1 (1.4)
E148Q/R761H 1 (1.4)
Total 70 (100)
parameters in children with FMF. Turkmen et al. indi-
cated that colchicine therapy caused a slight but signifi-
cant increase in BMI. There was no obese child among
the FMF subjects in this study. In the light of sugges-
tions that obesity is in fact a result of inflammatory dis-
ease, we think that the chronic inflammatory situation
alone is not enough to state the mechanism of the
non-development of obesity in the FMF study group.
The low-grade systemic inflammation in FMF patients
may underlie the clustering of metabolic risk factors,
but their role in children remains to be specified. The
adipocytokines and cytokines appear to be important in
this respect.
Leptin is secreted from adipocytes in response to
changes in body fat and was initially suggested as a
promising “anti-obesity” hormone. The interaction of
leptin with its receptors controls body weight and daily
energy consumption [19,20]. In the hypothalamus, leptin
binds to receptors that stimulate anorexigenic peptides
and inhibit orexigenic peptides [21]. Leptin declines
rapidly during fasting. Therefore, leptin deficiency was
perceived as a state of unmitigated starvation, leading to
compensatory responses, such as hyperphagia, decreased
metabolic rate and changes in hormone levels, designed
to restore energy balance [22]. Leptin reduces intracellu-
lar lipid levels in skeletal muscle, liver and pancreatic beta
cells, and thereby improving insulin sensitivity.
Unlike most adipokines, adiponectin expression and
serum concentrations are reduced in obese and insu-
lin-resistant states. Like leptin, adiponectin enhances
insulin sensitivity. High adiponectin levels were found in
F. Gök et al. / HEALTH 2 (2010) 268-271
Copyright © 2010 SciRes Openly accessible at http://www.scirp.org/journal/HEALTH/
association with high levels of HDL cholesterol and a
low triglyceride-to-HDL ratio [23]. Adiponectin, impli-
cated as having anti-inflammatory activity, is induced by
PPARg (Peroxisome proliferator-activated receptors) ago-
nism. Weight loss and caloric restriction have been found
to increase adiponectin plasma levels and gene expres-
sion in white adipose tissue. Two case control studies in
obesity-prone Pima Indians and in Caucasians suggested
that individuals with high adiponectin concentrations are
less likely to develop type-2 diabetes than those with
low concentrations [22]. Also, Saltevo et al. showed the
significant negative relationship between adiponectin
measured at adulthood and the relative change of BMI
from childhood to adulthood [24].
It was shown that insulin resistance in lipoatrophic
mice was fully reversed by a combination of physio-
logical doses of adiponectin and leptin, but only partially
by either adiponectin or leptin alone, suggesting that
adiponectin and leptin work together to sensitize periph-
eral tissues to insulin. However, because globular adi-
ponectin improves insulin resistance but not obesity in
ob/ob leptin-deficient mice, adiponectin and leptin ap-
pear to have distinct, albeit overlapping, functions [22].
Another adipokine studied in obese patients is omentin.
Lean subjects have higher plasma omentin levels than do
obese and overweight patients. Plasma omentin levels are
inversely correlated with BMI, waist circumference, leptin
levels and insulin resistance as measured by HOMA-R,
and positively correlated with adiponectin and HDL-
cholesterol levels. Accordingly, omentin gene expression
is decreased with obesity [25].
In addition, adipokines and many cytokines (espe-
cially IL-17A, IL-6, TNF-alfa) also were studied and
found to be associated with lipid metabolism. It was
shown that IL-17A inhibits adipocyte differentiation in
human bone marrow mesenchymal stem cells, while
promoting lipolysis of differentiated adipocytes [26].
In conclusion, the chronic inflammatory situation
alone is not sufficient to state the mechanism of the non-
development of obesity in FMF patients. It is thought
that some unligteening molecular mechanisms are in-
volved in the interaction between cytokines and adipo-
cytokines preventing obesity in FMF patients. Due to the
limited number of patients in this study, further research
with a greater number of patients looking at the wide
range of adipocytokines and cytokines known to be as-
sociated with lipid metabolism and obesity are needed to
confirm this speculation and establish the fundamentals
of the non-development of obesity in FMF patients.
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