
DUAL EFFECT OF THE GHRL GENE VARIANT IN
THE MOLECULAR PATHOGENESIS OF OBESITY Becer E1,2, Ergoren MC2,3,* *Corresponding Author: Associate Professor Mahmut C. Ergoren, Ph.D., Department of Medical
Biology, Faculty of Medicine, Near East University, Near East Boulevard, 99138 Nicosia, Cyprus.
Tel.: +90-392-675-1000, Ext: 3035. Fax: +90-392-223-6461. Mobile: +90-0548-865-8889. E-mail:
mahmutcerkez.ergoren@ neu.edu.tr page: 27
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RESULTS
Demographic Statistics and Biochemical
Parameters. The demographic characteristics and biochemical
parameters of the studied individuals are shown
in Table 2. This case-control study comprised 211 Turkish-
Cypriots (106 obese and 95 non obese). One hundred and
six obese adult patients with an age of 41.56 ± 9.87 and
BMI of 41.58 ± 4.93 kg/m2 were a generated case group.
The control group included 95 non obese subjects with the
mean age of 39.03 ± 9.45 years and BMI mean was 22.61 ±
1.82 kg/m2. There was no statistical difference of gender between
the two groups. The statistically significant difference
between biochemical parameters including fasting glucose,
TC, LDL-C, HDL-C, TG and HOMA-IR was observed between obese and non obese (p <0.001 in all parameters)
as well as physical parameters of BMI, waist circumferences,
hip circumferences showed significant difference (p
<0.001 in all parameters) except age (p = 0.066) Table 2).
Genotype Distribution and Allele Frequencies of
the GHRL Gene Variants (Arg51Gln and Leu72Met) in
the Studied Population. The allele frequencies and genotype
distributions of the GHRL rs34911341 (C>T) (Arg51
Gln) and rs696217 (G>T) (Leu72Met) gene variants are
shown in Table 3. Distribution of the GHRL rs34911341
(C>T) genotypes were 98.12% for CC, 0.94% for CT and
0.94% for TT in the obese group. The frequencies of CC,
CT and TT genotypes were 95, 0.0 and 0.0%, respectively,
in non obese subjects. There was significant deviation of
genotypic distribution from HWE in obese subjects (χ2 =
46.43, p <0.05). The deficit of the CT genotype frequencies
in obese subjects probably accounts for the deviation from
HWE. No significant difference in genotype frequencies
of the rs34911341 polymorphism was detected between
obese and non obese subjects (p = 0.40).
On the other hand, the rs696217 (G>T) genotype
frequencies were calculated and are shown in Table 3. In
obese subjects, the genotype frequencies were 34.91% for
GG, 53.77% for GT and 11.32% for TT. The frequencies
of GG, GT and TT genotypes were 60, 35.79 and 4.12%,
respectively, in non obese subjects. There were no significant
deviation of genotypic distribution from HWE in
both obese (χ2 = 2.04, p = 0.15) and non obese subjects
(χ2 = 0.14, p = 0.7). A significant difference in genotype
frequencies of the rs696217 polymorphism was detected
between obese and non obese subjects (p = 0.0012).
However, the results were in agreement with the global
minor allele frequency (MAF) observations by Ensembl
Genome Browser [29]. The MAF of GHRL rs696217 T
allele was determined as ~38.0% in obese patients and
~22.0% in non obese individuals. The case-control genetic
association analysis indicated a statistically significant
difference in the allele frequencies of the GHRL rs696217
(G>T) variant between obese and non obese subjects [p =
0.0005; odds ratio (OR) = 0.459; 95% confidence interval
(95% CI) = 0.295-0.713] (Table 3).
Associations Between the GHRL Leu72Met Gene
Polymorphisms and Clinical Parameters. The genotype
distributions of all studied subjects were tested according
to anthropometric and metabolic characteristics. The
GHRL rs696217 T allele that substituted Leu→Met at position
72 was found to be significant when associated with
waist circumference and hip circumference levels in the
population (p = 0.005, p = 0.002, respectively) (Table 4).
No other statistically significant parameter was observed
in other clinical characteristics except for HDL-C (p =
0.018). Strikingly, subjects with the rs696217 GT genotype
(heterozygous) had significantly lower HDL-C (p = 0.015)
than GG (wild type) subjects (Table 4).
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