Association of IL8 and IL10 gene allelic variants with ischemic stroke risk and prognosis
Aim. Evaluating a role of IL8 gene –781 C/T, and IL10 gene –592C/A polymorphisms as genetic markers of ischemic stroke risk. Methods. A case group consisted of 183 patients with ischemic stroke, which were treated in the Brain Vascular Pathology unit of SI «Institute of Gerontolo...
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Інститут молекулярної біології і генетики НАН України
2014
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| Цитувати: | Association of IL8 and IL10 gene allelic variants with ischemic stroke risk and prognosis / A.M. Kucherenko, D.V. Shulzhenko, S.M. Kuznetsova, S.V. Demydov, L.A. Livshits // Вiopolymers and Cell. — 2014. — Т. 30, № 3. — С. 234-238. — Бібліогр.: 14 назв. — англ. |
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irk-123456789-1543052019-06-16T01:28:36Z Association of IL8 and IL10 gene allelic variants with ischemic stroke risk and prognosis Kucherenko, A.M. Shulzhenko, D.V. Kuznetsova, S.M. Demydov, S.V. Livshits, L.A. Biomedicine Aim. Evaluating a role of IL8 gene –781 C/T, and IL10 gene –592C/A polymorphisms as genetic markers of ischemic stroke risk. Methods. A case group consisted of 183 patients with ischemic stroke, which were treated in the Brain Vascular Pathology unit of SI «Institute of Gerontology of NAMS of Ukraine». A control group included 88 healthy individuals older than 65 years without any history of ischemic stroke. Genotyping was performed using PCR followed by restriction fragment length polymorphism analysis. Results. Significantly (P < 0,05) higher frequency of IL8 –781T allele carriers in the case group (81,6 %) comparing to the control (70,1%) was revealed. –781T allele carriers have nearly 2-fold increased ischemic stroke development risk (OR = 1.886; 95 % CI: 1.041–3.417). Significantly (P < 0,05) higher frequency of IL10 gene –592C allele carriers was observed in the patients with ischemic stroke (98,2%) comparing to the control (90,7 %). The ischemic stroke development risk in such individuals is 5-fold increased (OR = 5.71; 95 % CI: 1.48–22.11). It was revealed that –592C allele homozygotes with ischemic stroke have more than 2-fold higher improvement (according to the Rankin scale) chances during the first fortnight of treatment (OR = 2,76; 95 % CI: 1,26–6,07). Conclusions. On the basis of the obtained significant differences, IL8 gene –781T and IL10 gene –592C variants may be considered the factors of ischemic stroke hereditary susceptibility. Besides, IL10 gene –592CC genotype is a genetic marker of the patients state positive dynamics during first two weeks of treatment. Мета. Оцінити роль поліморфних варіантів –781C/T гена IL8 і –592C/A гена IL10 як генетичних маркерів ризику розвитку ішемічного інсульту. Методи. До групи дослідження ввійшли 183 пацієнти з ішемічним інсультом, які перебували на стаціонарному лікуванні у відділенні судинної патології головного мозку ДУ «Інститут геронтології НАМН України»; до контрольної – 88 здорових людей старше 65 років без історії ішемічного інсульту. Генотипування проводили методом ПЛР з наступним аналізом поліморфізму довжини рестрикційних фрагментів. Результати. Виявлено статистично достовірно (P < 0,05) вищу частоту носіїв алеля IL8 –781T у групі пацієнтів з інсультом (81,6 %) порівняно з контрольною групою (70,1 %). Носії алеля IL8 –781Т мають майже вдвічі вищий ризик розвитку ішемічного інсульту (OR = 1,886; ДІ 95 %: 1,041–3,417). Статистично достовірно (P < 0,05) вища частота носіїв алеля –592C гена IL10 спостерігалась у пацієнтів з ішемічним інсультом (98,2 %) порівняно з контрольною групою (90,7 %). Ризик розвитку ішемічного інсульту (OR = 5,71; ДІ 95 %: 1,48–22,11) у носіїв цього алеля у 5 разів вищий. Встановлено, що в осіб, гомозиготних за алелем –592С гена IL10, у яких розвинувся ішемічний інсульт, шанси на покращення стану (за шкалою Ренкіна) протягом перших двох тижнів майже втричі більші (OR = 2,76; ДІ 95 %: 1,26–6,07). Висновки. На підставі отриманих статистичних відмінностей встановлено, що алелі –781T гена IL8 і –592С гена IL10 є факторами спадкової схильності до розвитку ішемічного інсульту. Крім того, генотип –592СС гена IL10 є генетичним маркером позитивної динаміки стану пацієнта у перші два тижні лікування. Цель. Оценить роль полиморфных вариантов –781C/T гена IL8 и –592C/A гена IL10 в качестве генетических маркеров риска развития ишемического инсульта. Методы. В исследуемую группу вошли 183 пациента с ишемическим инсультом, находившихся на стационарном лечении в отделении сосудистой патологии головного мозга ГУ «Институт геронтологии НАМН Украины»; в контрольную –88 здоровых людей старше 65 лет без истории ишемического инсульта. Генотипирование проводили методом ПЦР с последующим анализом полиморфизма длины рестрикционных фрагментов. Результаты. Выявлено статистически достоверно (P < 0,05) более высокую частоту носителей аллеля IL8 –781Т в группе пациентов с инсультом (81,6 %) по сравнению с контрольной группой (70,1 %). Риск развития ишемического инсульта у носителей аллеля IL8 –781Т почти вдвое выше (OR = 1,886; ДИ 95 %: 1,041–3,417). Статистически достоверно (P < 0,05) более высокая частота носителей аллеля –592C гена IL10 наблюдалась у пациентов с ишемическим инсультом (98,2 %) по сравнению с контрольной группой (90,7 %). Риск развития ишемического инсульта у носителей этого аллеля в 5 раз выше (OR = 5,71; ДИ 95 %: 1,48–22,11). Установлено, что у лиц, гомозиготных по аллелю –592C гена IL10, у которых развился ишемический инсульт, шансы на улучшение состояния (по шкале Рэнкина) в течение первых двух недель почти втрое больше (OR = 2,76, ДИ 95 %: 1,26–6,07). Выводы. На основании полученных статистических различий установлено, что аллели –781T гена IL8 и –592С гена IL10 являются факторами наследственной предрасположенности к развитию ишемического инсульта. Кроме того, генотип –592СС гена IL10 является генетическим маркером положительной динамики состояния пациента в первые две недели лечения. 2014 Article Association of IL8 and IL10 gene allelic variants with ischemic stroke risk and prognosis / A.M. Kucherenko, D.V. Shulzhenko, S.M. Kuznetsova, S.V. Demydov, L.A. Livshits // Вiopolymers and Cell. — 2014. — Т. 30, № 3. — С. 234-238. — Бібліогр.: 14 назв. — англ. 0233-7657 DOI: http://dx.doi.org/10.7124/bc.00089B http://dspace.nbuv.gov.ua/handle/123456789/154305 575+575.111+575.22+577.13 en Вiopolymers and Cell Інститут молекулярної біології і генетики НАН України |
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Biomedicine Biomedicine Kucherenko, A.M. Shulzhenko, D.V. Kuznetsova, S.M. Demydov, S.V. Livshits, L.A. Association of IL8 and IL10 gene allelic variants with ischemic stroke risk and prognosis Вiopolymers and Cell |
| description |
Aim. Evaluating a role of IL8 gene –781 C/T, and IL10 gene –592C/A polymorphisms as genetic markers of ischemic stroke risk. Methods. A case group consisted of 183 patients with ischemic stroke, which were treated in the Brain Vascular Pathology unit of SI «Institute of Gerontology of NAMS of Ukraine». A control group included 88 healthy individuals older than 65 years without any history of ischemic stroke. Genotyping was performed using PCR followed by restriction fragment length polymorphism analysis. Results. Significantly (P < 0,05) higher frequency of IL8 –781T allele carriers in the case group (81,6 %) comparing to the control (70,1%) was revealed. –781T allele carriers have nearly 2-fold increased ischemic stroke development risk (OR = 1.886; 95 % CI: 1.041–3.417). Significantly (P < 0,05) higher frequency of IL10 gene –592C allele carriers was observed in the patients with ischemic stroke (98,2%) comparing to the control (90,7 %). The ischemic stroke development risk in such individuals is 5-fold increased (OR = 5.71; 95 % CI: 1.48–22.11). It was revealed that –592C allele homozygotes with ischemic stroke have more than 2-fold higher improvement (according to the Rankin scale) chances during the first fortnight of treatment (OR = 2,76; 95 % CI: 1,26–6,07). Conclusions. On the basis of the obtained significant differences, IL8 gene –781T and IL10 gene –592C variants may be considered the factors of ischemic stroke hereditary susceptibility. Besides, IL10 gene –592CC genotype is a genetic marker of the patients state positive dynamics during first two weeks of treatment. |
| format |
Article |
| author |
Kucherenko, A.M. Shulzhenko, D.V. Kuznetsova, S.M. Demydov, S.V. Livshits, L.A. |
| author_facet |
Kucherenko, A.M. Shulzhenko, D.V. Kuznetsova, S.M. Demydov, S.V. Livshits, L.A. |
| author_sort |
Kucherenko, A.M. |
| title |
Association of IL8 and IL10 gene allelic variants with ischemic stroke risk and prognosis |
| title_short |
Association of IL8 and IL10 gene allelic variants with ischemic stroke risk and prognosis |
| title_full |
Association of IL8 and IL10 gene allelic variants with ischemic stroke risk and prognosis |
| title_fullStr |
Association of IL8 and IL10 gene allelic variants with ischemic stroke risk and prognosis |
| title_full_unstemmed |
Association of IL8 and IL10 gene allelic variants with ischemic stroke risk and prognosis |
| title_sort |
association of il8 and il10 gene allelic variants with ischemic stroke risk and prognosis |
| publisher |
Інститут молекулярної біології і генетики НАН України |
| publishDate |
2014 |
| topic_facet |
Biomedicine |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/154305 |
| citation_txt |
Association of IL8 and IL10 gene allelic variants with ischemic stroke risk and prognosis / A.M. Kucherenko, D.V. Shulzhenko, S.M. Kuznetsova, S.V. Demydov, L.A. Livshits // Вiopolymers and Cell. — 2014. — Т. 30, № 3. — С. 234-238. — Бібліогр.: 14 назв. — англ. |
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Вiopolymers and Cell |
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| fulltext |
UDC 575+575.111+575.22+577.13
Association of IL8 and IL10 gene allelic variants
with ischemic stroke risk and prognosis
A. M. Kucherenko1, 2, D. V. Shulzhenko3, S. M. Kuznetsova3,
S. V. Demydov2, L. A. Livshits1
1Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine
150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
2Educational and Scientific Center «Institute of Biology», Taras Shevchenko National University of Kyiv
64/13, Volodymyrska Str., Kyiv, Ukraine, 01601
3SI «Institute of Gerontology of National Academy of Medical Sciences of Ukraine»
67, Vyshgorodska Str., Kyiv, Ukraine, 04114
kucherenko.a.m@gmail.com
Aim. Evaluating a role of IL8 gene –781 C/T, and IL10 gene –592C/A polymorphisms as genetic markers of
ischemic stroke risk. Methods. A case group consisted of 183 patients with ischemic stroke, which were treated
in the Brain Vascular Pathology unit of SI «Institute of Gerontology of NAMS of Ukraine». A control group
included 88 healthy individuals older than 65 years without any history of ischemic stroke. Genotyping was
performed using PCR followed by restriction fragment length polymorphism analysis. Results. Significantly (P
< 0,05) higher frequency of IL8 –781T allele carriers in the case group (81,6 %) comparing to the control
(70,1%) was revealed. –781T allele carriers have nearly 2-fold increased ischemic stroke develop- ment risk
(OR = 1.886; 95 % CI: 1.041–3.417). Significantly (P < 0,05) higher frequency of IL10 gene –592C allele
carriers was observed in the patients with ischemic stroke (98,2%) comparing to the control (90,7 %). The
ischemic stroke development risk in such individuals is 5-fold increased (OR = 5.71; 95 % CI: 1.48–22.11). It
was revealed that –592C allele homozygotes with ischemic stroke have more than 2-fold higher improvement
(according to the Rankin scale) chances during the first fortnight of treatment (OR = 2,76; 95 % CI: 1,26–6,07).
Conclusions. On the basis of the obtained significant differences, IL8 gene –781T and IL10 gene –592C variants
may be considered the factors of ischemic stroke hereditary susceptibility. Besides, IL10 gene –592CC genotype
is a genetic marker of the patients state positive dynamics during first two weeks of treatment.
Keywords: interleukin, ischemic stroke, polymorphism.
Introduction. Inflammation is a key process in orga-
nism protection, which is activated in response to diffe-
rent traumas and injuries [1]. Cerebral ischemia indu-
ces quick inflammatory reaction involving several cell
types [1]. The whole range of modern studies is focused
on ischemia-related inflammatory signaling proving its
involvement in all stages of the ischemic cascade [2].
Cytokine environment (a network of interacting cytoki-
nes and their receptors) is a crucial contributor to the in-
flammatory response and thus is closely connected to
the pathophysiology of ischemia-induced brain injury,
especially ischemic stroke. The balance between pro-
and anti-inflammatory cytokines is significantly altered
by changes in respective gene expression mostly due to
polymorphisms in their promoter and intron regions [3,
4]. In order to investigate certain interleukin role in the
stroke pathogenesis two genes were chosen: pro-inflam-
matory interleukin 8 (IL8) and anti-inflammatory inter-
leukin 10 (IL10). Interleukin 8 is a cytokine of chemoat-
traction, which also functions as growth and angiogene-
sis factor. It induces immune cell infiltration in ische-
mia zone and may participate in reperfusion [5]. IL8 ge-
ne is located on chromosome 4 in position 4q13–q21 and
consists of 4 exons and 3 introns [6]. The total amount
234
ISSN 0233–7657. Biopolymers and Cell. 2014. Vol. 30. N 3. P. 234–238 doi: http://dx.doi.org/10.7124/bc.00089B
� Institute of Molecular Biology and Genetics, NAS of Ukraine, 2014
of 235 SNPs is reported for this gene [7]. A common C
to T transition in position –781 of first intron in IL8 ge-
ne creates a recognition site for the transcription factor
C/EBP� that affects the expression and leads to a high-
er production of the respective protein [8]. Therefore, it
was selected as a possible genetic marker of the ische-
mic stroke risk. Interleukin 10 is an anti-inflammatory
cytokine associated with the tissue repair and cytopro-
tective effects [9]. IL10 gene is located on chromosome
1 in position 1q31–q32. It consists of 5 exons and 4 in-
trons [10]. The total amount of 187 SNPs is reported for
this gene [7]. A promoter variant –592C/A is located in
the Sp1 transcription factor recognition site leading to
an altered affinity of this factor to DNA sequence and
reduced level of the respective cytokine [11]. A func-
tional role of this polymorphic variant makes it a possib-
le genetic marker of the ischemic stroke risk.
The aim of this study was to evaluate the role of the
IL8 gene –781C/T, and IL10 gene –592C/A polymorphic
variants as genetic markers of the ischemic stroke risk.
Matherials and methods. Study groups. The case
group consisted of 183 patients with ischemic stroke
(men – 95, women – 88, average age – 64.6 ± 9.1). All
the patients have undergone examination and treatment
in the Brain Vascular Pathology unit of «Institute of Ge-
rontology of NAMS of Ukraine». The patients were do-
cumented according to a standard protocol comprising
the following information: medical history (including
general diseases and previous medication with particu-
lar reference to the vascular diseases); vascular risk fac-
tors (including hypertension, diabetes, cigarette smoking,
body mass index); results of clinical and instrumental
investigations (including carotid and vertebral ultra-
sound, electroencephalography, echocardiography, MRI
and CT); stroke cause and stroke severity as measured
by validated scales.
The control group included healthy individuals ol-
der than 65 years (n = 88, men – 35, women – 53, ave-
rage age – 73.9 ± 6.4) without the history of ischemic
stroke. The individuals comprising this group were sub-
jected to the standard interview including their medical
history and vascular risk factors.
All the participants were non-related and represen-
ted the general population of Ukraine without selection
on ethnical background. An informed consent was ob-
tained from each participant prior to blood collection
and DNA extraction. This study was approved by the
Ethical Committee of Institute of Molecular Biology
and Genetics of the National Academy of Sciences of
Ukraine.
Genotyping. The DNA was extracted from periphe-
ral blood leukocytes according to standard procedures.
Genotyping for the IL8 gene –781C/T, and IL10 gene
–592C/A polymorphisms was performed by the PCR
with following restriction fragment length polymor-
phism (RFLP) analysis as described elsewhere [8, 12].
Statistical analysis. The �2 test was used to detect
deviations from Hardy–Weinberg equilibrium in geno-
type distribution. Fisher’s exact test (Mid–P method)
was used to estimate the difference in genotype and alle-
lic distribution. In order to assess the association of cer-
tain genotype with ischemic stroke development OR in-
dex was calculated. A P-value of less than 0.05 was re-
garded as significant. Statistical analysis has been per-
formed using GenePop and OpenEpi statistical packa-
ges [13, 14].
Results and discussion. The observed genotype
distributions for two studied polymorphic variants did
not deviate from the ones expected according to the Har-
dy–Weinberg equilibrium in all investigated groups
(Table 1).
The analysis for the IL8 gene –781 C/T polymor-
phic variant revealed a significantly higher frequency
of –781T allele carriers in the case group (81.6 %) com-
paring to the control group (70.1 %). Further statistical
analysis showed that the carriers of IL8 –781T allele
have nearly 2-fold increased risk of ischemic stroke de-
velopment (OR = 1.89; CI 95 %: 1.04–3.42). The ob-
tained data may be explained as follows: the ischemic
injury is a result of the cellular and molecular events
cascade, caused by a lack of blood flow with further hy-
poxia [2, 9]. The hypoxic damage leads to the «danger
molecules» production by injured and dying cells – a
crucial trigger of post-ischemic immune system activa-
tion and ischemic area enlargement [9]. Pro-inflam-
matory interleukin 8 surplus that is characteristic of
–781T allele carriers may promote the expansion of is-
chemic injury area and its transformation to an infarction
zone.
The significantly higher frequency of the IL10 gene
–592C allele carriers was observed in the patients with
ischemic stroke (98.2 %) comparing to the control
235
IL8 AND IL10 GENE VARIANT ASSOCIATION WITH ISCHEMIC STROKE
group (90.7 %). The carriers of this allele have almost
6-fold increased risk of the ischemic stroke develop-
ment (OR = 5.71; 95 % CI: 1.47–22.11). The indivi-
duals carrying –592C allele may be assumed to have an
impaired primary inflammatory response to the cereb-
ral ischemia because of the anti-inflammatory interleu-
kin 10 increased level. The cerebral tissues, presumab-
ly, react slower to hypoxia under such conditions that
leads to the reperfusion delay and cell necrosis promo-
tion [2, 9].
In order to evaluate the role of individual’s genoty-
pe in the process of post-stroke improvement the geno-
type distributions for two studied polymorphic variants
have been analyzed in the group of patients with decrea-
sed stroke severity (assessed using Rankin scale on the
3rd and the 14th days of treatment) and no changes in a
state. The obtained results are presented in Table 2.
No association has been found between the IL8 ge-
ne –781C/T polymorphic variant genotype and the stro-
ke severity dynamics. Interestingly, the individuals ho-
mozygous for IL10 gene –592C allele have more than
2-fold higher chances of improvement during the first
two weeks of treatment (OR = 2.78; 95 % CI: 1.26–
6.12). The obtained results about the association of
–592C allele with the increased risk of ischemic stroke
and at the same time with the positive post-stroke im-
provement prognosis association may seem controver-
sial at the first glance. However, in fact these data ref-
236
KUCHERENKO A. M. ET AL.
Polymorphism Genotype
Case group Control group Odds Ratio
n % n % P OR 95 % CI
–781C/T IL8
gene
CC 33 18.4 26 29.9
0.04
0.53 0.29–0.96
CT 102 57.0 45 51.7
1.89 1.04–3.42
TT 44 24.6 16 18.4
Total 179 100 87 100 – – –
Allele – – –
C 168 46.9 55.7 – – –
T 190 53.1 44.3 – – –
Hardy–Weinberg
probability test;
P-value*
0.0694 0.8298 – – –
Genotype
–592C/A IL10
gene
CC 116 68.2 49 57.0
0.01
5.71 1.47–22.10
CA 51 30.0 29 33.7
0.18 0.05–0.68
AA 3 1.8 8 9.3
Total 170 100 86 100 – – –
Allele – – –
C 283 83.2 127 73.8 – – –
A 57 16.8 45 26.2 – – –
Hardy–Weinberg
probability test;
P-value*
0.4204 0.2625 – – –
N o t e. *Estimation of exact P- values conducted by the Markov chain method.
Table 1
Genotype and allele frequency for studied polymorphic variants with results for Hardy–Weinberg probability test and association tests
lect the contradictory roles of various inflammatory res-
ponses in cerebral ischemia. The inflammatory respon-
se during the acute phase of cerebral ischemia evokes
neuroprotective mechanisms through preconditioning,
which leads to the ischemic tolerance [1, 9]. The sup-
pression of pro-inflammatory pathways by high levels
of IL-10 during early stages of ischemic process may ha-
ve a detrimental effect. On the other hand, during later
stages of cerebral ischemia the beneficial aspects of in-
flammation are outbalanced by its contribution to the is-
chemic lesion progression. The pro-inflammatory cyto-
kine (interleukin 6, 8, 1 �) production induces the in-
flammatory molecules expression and circulating lym-
phocyte infiltration in the area of cerebral infarction,
which results in the area expansion. Anti-inflammatory
interleukin 10 negatively regulates the pro-inflamma-
tory cytokine production and thus may prevent injured
area enlargement [1, 2, 9].
Conclusions. On the basis of revealed significant
differences it was established that the IL8 gene –781T
and IL10 gene –592C variants may be considered the
genetic markers of the ischemic stroke development
risk. On the other hand, the IL10 gene –592CC genoty-
pe is associated with the positive post-stroke improve-
ment prognosis. Though, it is important to mention that
the final conclusion about the involvement of studied
markers in the cerebral ischemia pathogenesis would
be possible to make only after the verification of the ob-
tained results by independent study.
Funding. This work was supported by the National
Academy of Sciences of Ukraine [grant number
0110U000695].
Àñîö³àö³ÿ àëåëüíèõ âàð³àíò³â ãåí³â IL8 ³ IL10 ç ðèçèêîì ðîçâèòêó
³ ïðîãíîçîì ³øåì³÷íîãî ³íñóëüòó
À. Ì. Êó÷åðåíêî, Ä. Â. Øóëüæåíêî, Ñ. Ì. Êóçíºöîâà,
Ñ. Â. Äåìèäîâ, Ë. À. ˳âøèöü
Ðåçþìå
Ìåòà. Îö³íèòè ðîëü ïîë³ìîðôíèõ âàð³àíò³â –781C/T ãåíà IL8 ³
–592C/A ãåíà IL10 ÿê ãåíåòè÷íèõ ìàðêåð³â ðèçèêó ðîçâèòêó
237
IL8 AND IL10 GENE VARIANT ASSOCIATION WITH ISCHEMIC STROKE
Polemorphism Genotype
Case group Control group Odds Ratio
n % n % P OR 95 % CI
–781C/T IL8
gene
CC 6 11.0 26 22.6
0.08
0.43 0.16–1.11
CT 34 63.0 60 52.2
2.34 0.90–6.07
TT 14 25.9 29 25.2
Total 54 100 115 100 – – –
Allele – – –
C 46 42.6 112 48.7 – – –
T 62 57.4 118 51.3 – – –
Genotype
–592C/A IL10
gene
CC 43 81.1 65 60.7
0.01
2.78 1.26–6.12
CA 10 18.9 39 36.5
0.36 0.16–0.79
AA 0 0.0 3 2.8
Total 53 100 107 100 – – –
Allele – – –
C 96 90.6 169 79.0 – – –
A 10 9.4 45 21.0 – – –
Table 2
Genotype and allele frequency for studied polymorphic variants and results of association tests in patients with improved state by the 14
th
day
of treatment and patients with no changes in stroke severity
³øåì³÷íîãî ³íñóëüòó. Ìåòîäè. Äî ãðóïè äîñë³äæåííÿ ââ³éøëè 183
ïàö³ºíòè ç ³øåì³÷íèì ³íñóëüòîì, ÿê³ ïåðåáóâàëè íà ñòàö³îíàðíî-
ìó ë³êóâàíí³ ó â³ää³ëåíí³ ñóäèííî¿ ïàòîëî㳿 ãîëîâíîãî ìîçêó ÄÓ
«²íñòèòóò ãåðîíòîëî㳿 ÍÀÌÍ Óêðà¿íè»; äî êîíòðîëüíî¿ – 88
çäîðîâèõ ëþäåé ñòàðøå 65 ðîê³â áåç ³ñòî𳿠³øåì³÷íîãî ³íñóëüòó.
Ãåíîòèïóâàííÿ ïðîâîäèëè ìåòîäîì ÏËÐ ç íàñòóïíèì àíàë³çîì
ïîë³ìîðô³çìó äîâæèíè ðåñòðèêö³éíèõ ôðàãìåíò³â. Ðåçóëüòàòè.
Âèÿâëåíî ñòàòèñòè÷íî äîñòîâ³ðíî (P < 0,05) âèùó ÷àñòîòó
íîñ³¿â àëåëÿ IL8 –781T ó ãðóï³ ïàö³ºíò³â ç ³íñóëüòîì (81,6 %)
ïîð³âíÿíî ç êîíòðîëüíîþ ãðóïîþ (70,1 %). Íîñ³¿ àëåëÿ IL8 –781Ò
ìàþòü ìàéæå âäâ³÷³ âèùèé ðèçèê ðîçâèòêó ³øåì³÷íîãî ³íñóëüòó
(OR = 1,886; IJ 95 %: 1,041–3,417). Ñòàòèñòè÷íî äîñòîâ³ðíî (P
< 0,05) âèùà ÷àñòîòà íîñ³¿â àëåëÿ –592C ãåíà IL10 ñïîñòåð³ãà-
ëàñü ó ïàö³ºíò³â ç ³øåì³÷íèì ³íñóëüòîì (98,2 %) ïîð³âíÿíî ç êîí-
òðîëüíîþ ãðóïîþ (90,7 %). Ðèçèê ðîçâèòêó ³øåì³÷íîãî ³íñóëüòó
(OR = 5,71; IJ 95 %: 1,48–22,11) ó íîñ³¿â öüîãî àëåëÿ ó 5 ðàç³â âè-
ùèé. Âñòàíîâëåíî, ùî â îñ³á, ãîìîçèãîòíèõ çà àëåëåì –592Ñ ãåíà
IL10, ó ÿêèõ ðîçâèíóâñÿ ³øåì³÷íèé ³íñóëüò, øàíñè íà ïîêðàùåííÿ
ñòàíó (çà øêàëîþ Ðåíê³íà) ïðîòÿãîì ïåðøèõ äâîõ òèæí³â ìàéæå
âòðè÷³ á³ëüø³ (OR = 2,76; IJ 95 %: 1,26– 6,07). Âèñíîâêè. Íà
ï³äñòàâ³ îòðèìàíèõ ñòàòèñòè÷íèõ â³äì³í- íîñòåé âñòàíîâëåíî,
ùî àëåë³ –781T ãåíà IL8 ³ –592Ñ ãåíà IL10 º ôàêòîðàìè ñïàäêîâî¿
ñõèëüíîñò³ äî ðîçâèòêó ³øåì³÷íîãî ³íñóëüòó. Êð³ì òîãî, ãåíîòèï
–592ÑÑ ãåíà IL10 º ãåíåòè÷íèì ìàðêåðîì ïîçèòèâíî¿ äèíàì³êè
ñòàíó ïàö³ºíòà ó ïåðø³ äâà òèæí³ ë³êóâàííÿ.
Êëþ÷îâ³ ñëîâà: ³íòåðëåéê³í, ³øåì³÷íèé ³íñóëüò, ïîë³ìîðô³çì.
Àññîöèàöèÿ àëëåëüíûõ âàðèàíòîâ ãåíîâ IL8 è IL10 ñ ðèñêîì
ðàçâèòèÿ è ïðîãíîçîì èøåìè÷åñêîãî èíñóëüòà
À. Ì. Êó÷åðåíêî, Ä. Â. Øóëüæåíêî, Ñ. Ì. Êóçíåöîâà,
Ñ. Â. Äåìèäîâ, Ë. À. Ëèâøèö
Ðåçþìå
Öåëü. Îöåíèòü ðîëü ïîëèìîðôíûõ âàðèàíòîâ –781C/T ãåíà IL8 è
–592C/A ãåíà IL10 â êà÷åñòâå ãåíåòè÷åñêèõ ìàðêåðîâ ðèñêà ðàç-
âèòèÿ èøåìè÷åñêîãî èíñóëüòà. Ìåòîäû.  èññëåäóåìóþ ãðóïïó
âîøëè 183 ïàöèåíòà ñ èøåìè÷åñêèì èíñóëüòîì, íàõîäèâøèõñÿ íà
ñòàöèîíàðíîì ëå÷åíèè â îòäåëåíèè ñîñóäèñòîé ïàòîëîãèè ãîëîâ-
íîãî ìîçãà ÃÓ «Èíñòèòóò ãåðîíòîëîãèè ÍÀÌÍ Óêðàèíû»; â êîí-
òðîëüíóþ – 88 çäîðîâûõ ëþäåé ñòàðøå 65 ëåò áåç èñòîðèè
èøåìè÷åñêîãî èíñóëüòà. Ãåíîòèïèðîâàíèå ïðîâîäèëè ìåòîäîì
ÏÖÐ ñ ïîñëåäóþùèì àíàëèçîì ïîëèìîðôèçìà äëèíû ðåñòðèêöè-
îííûõ ôðàãìåíòîâ. Ðåçóëüòàòû. Âûÿâëåíî ñòàòèñòè÷åñêè äîñ-
òîâåðíî (P < 0,05) áîëåå âûñîêóþ ÷àñòîòó íîñèòåëåé àëëåëÿ IL8
–781Ò â ãðóïïå ïàöèåíòîâ ñ èíñóëüòîì (81,6 %) ïî ñðàâíåíèþ ñ
êîíòðîëüíîé ãðóïïîé (70,1 %). Ðèñê ðàçâèòèÿ èøåìè÷åñêîãî èí-
ñóëüòà ó íîñèòåëåé àëëåëÿ IL8 –781Ò ïî÷òè âäâîå âûøå (OR =
1,886; ÄÈ 95 %: 1,041–3,417). Ñòàòèñòè÷åñêè äîñòîâåðíî (P <
0,05) áîëåå âûñîêàÿ ÷àñòîòà íîñèòåëåé àëëåëÿ –592C ãåíà IL10
íàáëþäàëàñü ó ïàöèåíòîâ ñ èøåìè÷åñêèì èíñóëüòîì (98,2 %) ïî
ñðàâíåíèþ ñ êîíòðîëüíîé ãðóïïîé (90,7 %). Ðèñê ðàçâèòèÿ èøå-
ìè÷åñêîãî èíñóëüòà ó íîñèòåëåé ýòîãî àëëåëÿ â 5 ðàç âûøå (OR =
5,71; ÄÈ 95 %: 1,48–22,11). Óñòàíîâëåíî, ÷òî ó ëèö, ãîìîçèãîò-
íûõ ïî àëëåëþ –592C ãåíà IL10, ó êîòîðûõ ðàçâèëñÿ èøåìè÷åñêèé
èíñóëüò, øàíñû íà óëó÷øåíèå ñîñòîÿíèÿ (ïî øêàëå Ðýíêèíà) â òå-
÷åíèå ïåðâûõ äâóõ íåäåëü ïî÷òè âòðîå áîëüøå (OR = 2,76, ÄÈ 95
%: 1,26–6,07). Âûâîäû. Íà îñíîâàíèè ïîëó÷åííûõ ñòàòèñòè÷åñ-
êèõ ðàçëè÷èé óñòàíîâëåíî, ÷òî àëëåëè –781T ãåíà IL8 è –592Ñ ãåíà
IL10 ÿâëÿþòñÿ ôàêòîðàìè íàñëåäñòâåííîé ïðåäðàñïîëîæåííîñ-
òè ê ðàçâèòèþ èøåìè÷åñêîãî èíñóëüòà. Êðîìå òîãî, ãåíîòèï
–592ÑÑ ãåíà IL10 ÿâëÿåòñÿ ãåíåòè÷åñêèì ìàðêåðîì ïîëîæè-
òåëüíîé äèíàìèêè ñîñòîÿíèÿ ïàöèåíòà â ïåðâûå äâå íåäåëè ëå÷å-
íèÿ.
Êëþ÷åâûå ñëîâà: èíòåðëåéêèí, èøåìè÷åñêèé èíñóëüò, ïîëè-
ìîðôèçì.
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