POLYMORPHISM OF THE IL13 GENE MAY BE
ASSOCIATED WITH UTERINE LEIOMYOMAS
IN SLOVENIAN WOMEN Krsteski J, Jurgec S, Pakiž M, But I, Potočnik U, *Corresponding Author: Professor Uroš Potočnik, Ph.D., Centre for Human Molecular Genetics and Pharmacogenomics,
Faculty of Medicine, University of Maribor, Taborska Ulica 8, 2000 Maribor, Slovenia. Tel: +386-2-2345-854, Fax: +386-2-
2345-820, E-mail: uros.potocnik@um.si page: 51
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RESULTS
Association Analysis of Selected Single Nucleotide
Polymorphisms. We found statistically significant
differences between the SNP rs20541 of gene IL13 and
ULM patients. The genotyping of IL13 and other genes
was performed by HRM or RFLP analyses, as described
in Materials and Methods and shown in Figure 1. The
frequency of the TT genotype of rs20541 was higher in
the group of healthy controls (8.7%) compared to all patients
with ULM (1.0%) (p = 0.018, OR = 0.184, 95% CI
= 0.048-0.712) using the recessive genotype model (TT
vs. CT+CC). We also found a higher frequency of the TT
genotype of rs 20541 in all controls (6.8%) compared to
patients with multiple ULM, for which the frequency of
the TT genotype was 1.0% using the recessive genotype
model (TT vs. CT+CC) (p = 0.048, OR = 0.145, 95% CI =
0.018-1.165). The association was also statistically significant
when comparing multiple ULM, where the frequency
of the TT genotype was (1.0%) and healthy individuals
from the normal population, where the frequency of the
TT genotype was (8.7%) (p = 0.017, OR = 0.111, 95%
CI = 0.014-0.902) using the recessive genotype model
(TT vs. CT+ CC). Power of association analysis between
phenotype (ULM vs. all controls) and dominant (CC vs.
CT+TT) or recessive (CC+CT vs. TT) genetic models of
rs20541 was p = 0.381 and p = 0.940, respectively. For
other tested SNPs, there were no significant differences
in genotype or allele frequencies between patients and
controls. Results of association analyses for rs20541 of
the IL13 gene are shown in Tables 2 and 3.
Association Between Evaluated Single Nucleotide
Polymorphisms and Clinical Characteristics. When we
compared selected SNPs with clinical characteristics of patients
within a particular phenotype groups, differences were
found between solitary and multiple ULM. In solitary ULM,
rs1801275 (IL4R) was associated with the age at first sexual
intercourse (p = 0.004) where median age at first intercourse
of patients exhibiting the GG genotype was 19 years and the
age of patients exhibiting either the AA or AG genotype was
18. In multiple ULM, rs1801275 (IL4R) was associated with
the age at diagnosis (p = 0.003) where patients with the GG
genotype were younger at diagnosis (27.5 years) compared
to patients with the AA or AG genotype (45 years).
The SNP rs6887695 (IL12B) was associated with
parity for solitary and multiple ULM subtypes. In solitary
ULM, an association was found using the C vs. G allele
model (p = 0.029) and using the CC vs. CG+GG genetic model (p = 0.016). On average, patients with the C allele
or CC genotypes had a parity of one and patients with the
G allele or the CG or GG genotypes had a parity of two.
In multiple ULM, an association was detected for the C
vs. G allele model (p = 0.049) and for the CC vs. CG+GG
genetic model (p = 0.048). On average, patients with the
C allele or CC genotype had a parity of two, and patients
with the G allele or CG or GG genotypes had a parity of
one. In multiple ULM, rs20541 (IL13) was associated with
17β-estradiol serum levels in the follicular phase of the
menstrual cycle (p = 0.003) where patients with the CC
genotype had a higher 17β-estradiol levels (0.525 nmol/L)
compared to patients with either the CT or TT genotypes
(0.130 nmol/L).
In addition, rs11575934 (IL12RB1) was also associated
with parity in multiple ULM. An association was
found for the A vs. G allele model (p = 0.004) and in AA
vs. AG+ GG genetic model (p = 0.009). On average, patients
with the A allele and AA genotypes had a parity of
two, and patients with the G allele or AG or GG genotypes
had a parity of one.
Logistic Regression Analyses. To further investigate
possible parameters that are associated with increased risk
of ULM development, we performed logistic regression
analyses of selected genetic and clinical parameters in
relation to solitary and multiple ULM occurrence (Table
4). For SNP rs1801275 (IL4R), association was found in
allele and genotype genetic model with the ULM phenotype
subgroups, where carrying the G allele (OR = 3.641,
p = 2.19 × 10-2) or genotypes AG or GG (OR = 6.975, p
= 7.49× 10-3), presence of adenomyosis (OR = 11.315,
p = 4.55 × 10-3), higher age at diagnosis (OR = 1.086, p
= 3.24 × 10-2), positive family history (OR = 0.152, p =
3.03 × 10-3), earlier menarche (OR = 0.401, p = 2.10 ×
10-4), lower number of pregnancies (OR = 0.559, p = 1.99
× 10-2) and lower age at first sexual intercourse (OR =
0.655, p = 1.81 × 10-2), all increase the risk of multiple
ULM development.
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