Association of genotypes by polymorphic variant C-108T of PON1 gene with the risk of developing breast cancer and hypertensive disease in women
Aim. To analyze the effect of the polymorphic variant C-108T of PON1 gene on the risk of developing breast cancer (BC) and hypertensive disease (HD) in women. Methods. 130 women with non-complicated HD of degree II and 131 women with BC of I and II stages without cardiovascular complications were en...
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nasplib_isofts_kiev_ua-123456789-1544282025-02-23T19:14:24Z Association of genotypes by polymorphic variant C-108T of PON1 gene with the risk of developing breast cancer and hypertensive disease in women Асоціація генотипів за поліморфним варіантом С-108Т гена PON1 з ризиком розвитку раку молочної залози та гіпертонічної хвороби у жінок Ассоциация генотипов полиморфного варианта С-108Т гена PON1 с риском развития рака молочной железы и гипертонической болезни у женщин Fishchuk, L.Ye. Biomedicine Aim. To analyze the effect of the polymorphic variant C-108T of PON1 gene on the risk of developing breast cancer (BC) and hypertensive disease (HD) in women. Methods. 130 women with non-complicated HD of degree II and 131 women with BC of I and II stages without cardiovascular complications were enrolled in the study. The control group was composed of 102 women without cardiovascular and oncological pathologies. Molecular-genetic analysis was performed on DNA isolated from the samples of peripheral blood. Genotyping of polymorphic variant C-108T of PON1 gene was carried out with the use of PCR-RFLP method. Results. It has been revealed that the presence of -108CC genotype of PON1 gene in women elevates the risk of HD development in more than 1.5 times. As for women over 54, the presence of -108CC genotype of PON1 gene is associated with a decreased risk of BC by almost 4 times and, in contrary, the presence of -108CT genotype of PON1 gene is associated with an increased risk of BC by more than 3 times. Conclusions. Polymorphic variant C-108T of PON1 gene may be considered as possible prognostic marker of BC and HD development in women. Мета. Проаналізувати вплив поліморфного варіанта С-108Т гена PON1 на ризик розвитку раку молочної залози (РМЗ) та гіпертонічної хвороби (ГХ) у жінок. Методи. До дослідження залучено 130 жінок з діагнозом ГХ ІІ ступеня з неускладненим перебігом та 131 жінку з діагнозом РМЗ I і ІІ стадій без серцево-судинних ускладнень. До контрольної групи увійшли 102 жінки без серцево-судинної та онкологічної патологій. Для молекулярно-генетичного аналізу використано ДНК, виділену з лейкоцитів периферійної крові. Генотипування за поліморфним варіантом С-108Т гена PON1 проводили із застосуванням методу ПЛР-ПДРФ. Результати. Встановлено, що наявність генотипу -108СС гена PON1 у жінок асоційована зі зниженням ризику розвитку ГХ більш ніж у 1,5 разу. Для жінок, старших 54 років, наявність генотипу -108СС гена PON1 асоційована із зменшенням ризику розвитку РМЗ майже у 4 рази, а наявність генотипу -108СТ гена PON1, навпаки, пов’язана зі зростанням ризику розвитку РМЗ більш ніж у 3 рази. Висновки. Поліморфний варіант С-108Т гена PON1 є можливим прогностичним маркером ризику розвитку РМЗ та ГХ у жінок. Цель. Проанализировать влияние полиморфного варианта С-108Т гена PON1 на риск развития рака молочной железы (РМЖ) и гипертонической болезни (ГБ) у женщин. Методы. В исследовании участвовали 130 женщин с диагнозом ГБ II степени с неосложненным течением и 131 женщина с диагнозом РМЖ I и II стадий без сердечно-сосудистых осложнений. Контрольную группу составили 102 женщины без сердечно-сосудистой и онкологической патологий. Для молекулярно-генетического анализа использовали ДНК, выделенную из лейкоцитов периферической крови. Генотипирование по полиморфному варианту С-108Т гена PON1 проводили с применением метода ПЦР-ПДРФ. Результаты. Выявлено, что наличие генотипа -108СС гена PON1 у женщин ассоциировано со снижением риска развития ГБ более чем в 1,5 раза. Для женщин старше 54 лет наличие генотипа -108СС гена PON1 ассоциировано со снижением риска развития РМЖ почти в 4 раза, а наличие генотипа -108СТ гена PON1, наоборот, связано с возрастанием риска развития РМЖ более чем в 3 раза. Выводы. Полиморфный вариант С-108Т гена PON1 является возможным прогностическим маркером риска развития РМЖ и ГБ у женщин. 2014 Article Association of genotypes by polymorphic variant C-108T of PON1 gene with the risk of developing breast cancer and hypertensive disease in women / L.Ye. Fishchuk // Вiopolymers and Cell. — 2014. — Т. 30, № 4. — С. 310-313. — Бібліогр.: 12 назв. — англ. 0233-7657 DOI: http://dx.doi.org/10.7124/bc.0008A6 https://nasplib.isofts.kiev.ua/handle/123456789/154428 575.113:616.12-008.331.1:618.19-006.6-055.2(477) en Вiopolymers and Cell application/pdf Інститут молекулярної біології і генетики НАН України |
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Biomedicine Biomedicine |
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Biomedicine Biomedicine Fishchuk, L.Ye. Association of genotypes by polymorphic variant C-108T of PON1 gene with the risk of developing breast cancer and hypertensive disease in women Вiopolymers and Cell |
| description |
Aim. To analyze the effect of the polymorphic variant C-108T of PON1 gene on the risk of developing breast cancer (BC) and hypertensive disease (HD) in women. Methods. 130 women with non-complicated HD of degree II and 131 women with BC of I and II stages without cardiovascular complications were enrolled in the study. The control group was composed of 102 women without cardiovascular and oncological pathologies. Molecular-genetic analysis was performed on DNA isolated from the samples of peripheral blood. Genotyping of polymorphic variant C-108T of PON1 gene was carried out with the use of PCR-RFLP method. Results. It has been revealed that the presence of -108CC genotype of PON1 gene in women elevates the risk of HD development in more than 1.5 times. As for women over 54, the presence of -108CC genotype of PON1 gene is associated with a decreased risk of BC by almost 4 times and, in contrary, the presence of -108CT genotype of PON1 gene is associated with an increased risk of BC by more than 3 times. Conclusions. Polymorphic variant C-108T of PON1 gene may be considered as possible prognostic marker of BC and HD development in women. |
| format |
Article |
| author |
Fishchuk, L.Ye. |
| author_facet |
Fishchuk, L.Ye. |
| author_sort |
Fishchuk, L.Ye. |
| title |
Association of genotypes by polymorphic variant C-108T of PON1 gene with the risk of developing breast cancer and hypertensive disease in women |
| title_short |
Association of genotypes by polymorphic variant C-108T of PON1 gene with the risk of developing breast cancer and hypertensive disease in women |
| title_full |
Association of genotypes by polymorphic variant C-108T of PON1 gene with the risk of developing breast cancer and hypertensive disease in women |
| title_fullStr |
Association of genotypes by polymorphic variant C-108T of PON1 gene with the risk of developing breast cancer and hypertensive disease in women |
| title_full_unstemmed |
Association of genotypes by polymorphic variant C-108T of PON1 gene with the risk of developing breast cancer and hypertensive disease in women |
| title_sort |
association of genotypes by polymorphic variant c-108t of pon1 gene with the risk of developing breast cancer and hypertensive disease in women |
| publisher |
Інститут молекулярної біології і генетики НАН України |
| publishDate |
2014 |
| topic_facet |
Biomedicine |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/154428 |
| citation_txt |
Association of genotypes by polymorphic variant C-108T of PON1 gene with the risk of developing breast cancer and hypertensive disease in women / L.Ye. Fishchuk // Вiopolymers and Cell. — 2014. — Т. 30, № 4. — С. 310-313. — Бібліогр.: 12 назв. — англ. |
| series |
Вiopolymers and Cell |
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| fulltext |
UDC 575.113:616.12-008.331.1:618.19-006.6-055.2(477)
Association of genotypes by polymorphic variant
C-108T of PON1 gene with the risk of developing
breast cancer and hypertensive disease in women
L. Ye. Fishchuk
State Institute of Genetic and Regenerative Medicine, National Academy of Medical Sciences of Ukraine
67, Vyshgorods’ka Str., Kyiv, Ukraine, 04114
medgen@ukr.net
Aim. To analyze the effect of the polymorphic variant C-108T of PON1 gene on the risk of developing breast can-
cer (BC) and hypertensive disease (HD) in women. Methods. 130 women with non-complicated HD of degree II
and 131 women with BC of I and II stages without cardiovascular complications were enrolled in the study. The
control group was composed of 102 women without cardiovascular and oncological pathologies. Molecular-ge-
netic analysis was performed on DNA isolated from the samples of peripheral blood. Genotyping of polymorphic
variant C-108T of PON1 gene was carried out with the use of PCR-RFLP method. Results. It has been revealed
that the presence of -108CC genotype of PON1 gene in women elevates the risk of HD development in more than
1.5 times. As for women over 54, the presence of -108CC genotype of PON1 gene is associated with a decreased
risk of BC by almost 4 times and, in contrary, the presence of -108CT genotype of PON1 gene is associated with
an increased risk of BC by more than 3 times. Conclusions. Polymorphic variant C-108T of PON1 gene may be
considered as possible prognostic marker of BC and HD development in women.
Keywords: gene, PON1, breast cancer, hypertensive disease.
Introduction. According to the State Statistics Com-
mittee and the National Cancer Registry of Ukraine the
cardiovascular pathology and oncological neoplasms are
the main causes of mortality for women. The hypertensi-
ve disease (HD) ranks number one in the general structu-
re of the cardiovascular pathology, and the breast cancer
(BC) keeps the key place in the structure of the oncologi-
cal neoplasms among the female population of Ukraine.
Some works demonstrated that HD is associated
with the increased risk of developing the oncological
pathology, BC, in particular [1]. On the other hand, it
was determined that the antihypertensive therapy affects
the risk of developing BC and influences the survival in
patients with this pathology [2]. These data allow the
assumption that HD and BC are interrelated, i. e. their
development may be caused by similar pathological me-
chanisms. One of them can be the accumulation of free
radicals and their reactive metabolites at the oxidative
stress. One of important factors, promoting the forma-
tion of oxidative stress, is a decrease in the activity of
paraoxonase 1 (PON1), an enzyme, involved in the me-
tabolism of the oxygenated forms of lipids.
PON1 is the calcium-dependent hydrolase with bro-
ad substrate specificity, which is synthesized in the li-
ver and secreted into the plasma, where it binds to the
complex of high-density lipoproteins. It is known that
PON1 (through the hydrolysis of the oxygenated phos-
pholipids of the cellular membranes) prevents the oxy-
dic modification of low-density lipoproteins, decreases
the peroxides formation, and inhibits the cytokines pro-
duction and the monocytes adhesion to the endothelial
surface. The protective role of PON1 consists also in its
participation in the metabolism of homocysteine-thio-
lactone, a metabolite of homocysteine, which is cytoto-
xic for the organism [3–5]. The genetic polymorphism
in PON1 gene, coding PON1, is the main determinant
of interindividual variability of the enzyme activity.
PON1 is localized on the long arm of the chromosome
7q21.3. Among five polymorphic variants in the promo-
ter part of the gene, the replacement of C-108T (some-
310
ISSN 0233–7657. Biopolymers and Cell. 2014. Vol. 30. N 4. P. 310–313 doi: http://dx.doi.org/10.7124/bc.0008A6
� Institute of Molecular Biology and Genetics, NAS of Ukraine, 2014
times C-107T, rs705379) has the highest impact on the
PON1 activity in the plasma. In particular, it was
demonstrated to be approximately twice higher for the
people with the genotype -108CC compared to the
carriers of the genotype -108TT [3].
Up to date the associations of the polymorphic va-
riant C-108T of PON1 gene with the risks of cardio-
vascular diseases and oncological neoplasms have been
studied [6–8], but not in Ukraine. Therefore, the pur-
pose of our study was to analyze the effect of the poly-
morphic variant C-108T of PON1 gene on the risk of de-
veloping BC and HD in women.
Materials and methods. The study involved 130
women with the diagnosis of non-complicated HD of
degree II (group HD, average age – 48.57 ± 0.1) and 131
women with the diagnosis of BC of stages I and II with-
out cardiovascular complications (group BC, average
age – 43.21 ± 1.14). The control group included 102 wo-
men without cardiovascular and oncological pathologies
(control, average age – 47.86 ± 1.54). Later the groups
of women with BC and HD were divided into three age
subgroups: from 18 to 35 years (18–35, young women),
from 36 to 54 years (36–54, middle-aged women) and
older than 54 years (over 54, older age subgroup). The
control group was divided likewise (Table 1).
The work was approved by the Ethics Committee
of the State Institute of Genetic and Regenerative Me-
dicine of National Academy of Medical Sciences of Uk-
raine. All the women signed the informed consent form
for the study.
The peripheral blood leukocytes were used in the
molecular and genetic investigation. DNA isolation was
conducted using the commercial set «DNA-sorb-B» (the
Central Research Institute of Epidemiology, the Minist-
ry of Health Care of the Russian Federation). The geno-
typing of the polymorphic variant C-108T of PON1 ge-
ne was performed using the PCR-RFLP method (the po-
lymerase chain reaction and the restriction fragment
length polymorphism), according to the protocol, pre-
sented in the work of Grdic et al. [3] and adjusted to our
conditions. The fragment of 240 bp, obtained during
the amplification, was treated with the restriction endo-
nuclease BsrBI (Fermentas, Lithuania). The hydrolytic
degradation was performed for the fragment with variant
-108C, whereas the fragment with variant -108T remai-
ned undegraded.
The detection of the PCR-RFLP products was con-
ducted in 2 % agarose gel. The visualization of the re-
sults was performed in the ultraviolet light after stai-
ning with the ethidium bromide solution. The fragment
length was analyzed against the DNA marker (Figure).
The statistical processing of the data was conduc-
ted on the personal computer using the Statistica 10 and
MS Excel 2003 software. The Pearson criterion �
2 and
the Pearson criterion �
2 with Yates’s correction for the
continuity (for less than ten studies) were used to detect
reliable differences in the comparison of the frequency
of the investigated features for the groups of patients
and the control. The efficacy of genotype associations
by the polymorphic variant C-108T of PON1 gene with
the risk of developing diseases was estimated using the
value of the odds ratio (OR) in the range of 95 %
confidence interval (CI). The differences of p < 0.05
311
ASSOCIATION OF GENOTYPES BY POLYMORPHIC VARIANT C-108T OF PON1 GENE
Study group Number of people, n Average age, years
18–35 years
BC 53 30.6 ± 0.54
HD 22 31.23 ± 0.64
Control 33 29.24 ± 0.7
36–54 years
BC 52 46.39 ± 0.7
HD 70 47.04 ± 0.64
Control 23 45.87 ± 1.21
over 54 years
BC 26 62.58 ± 1.32
HD 38 61.42 ± 1.01
Control 46 62.22 ± 1.0
Table 1
The distribution of the main study groups depending on age
M 1 2 3 4 5 6 7
� 240
� 212
bp
The electrophoregram of the restriction fragment of PON1 gene
(C-108T) in 2 % agarose gel: Ì – DNA marker; samples 2, 5 – ge-
notype -108CC; samples 1, 3, 6 – genotype -108CT; samples 4, 7 –
genotype -108ÒÒ
were considered statistically reliable for all the types of
analysis.
Results and discussion. The molecular and genetic
study allowed determining the genotype frequencies by
the polymorphic variant C-108T of PON1 gene in the
women study groups (Table 2).
There was a reliable decrease in the frequency of ge-
notype -108CC of PON1 gene in the group of women
with HD compared to the control (�
2 = 4.06; p < 0.05;
OR = 0.55, 95 % CI: 0.31–0.99), which testifies to its
protective effect at the development of HD. Therefore,
our data confirm the assumption about the protective ef-
fect of genotype -108CC of PON1 gene, which is res-
ponsible for a high level of the PON1 activity with the
risk of developing a cardiovascular pathology.
The similar tendency in the distribution of the geno-
type frequencies by the polymorphic variant C-108T of
PON1 gene was observed for the patients with BC,
however the difference was not reliable (p > 0.05).
It is known that the HD incidence varies for diffe-
rent age groups of women. For instance, it is conside-
rably higher after 35 and is most common for the wo-
men over 54. On the other hand, a great number of BC
cases are diagnosed after 36. It may be explained by the
fact that approximately at this age there are involutive
changes in the structure of mammary glands resulting
in the replacement of the glandular tissue with adipose
and/or fibrous tissue. The women after 35 are also no-
table for rapid progression of fertility impairment, de-
termined by the hormonal changes, i. e. a disbalance, fol-
lowed by an acute deficiency of female sex hormones,
estrogens and progesterone. Taking the abovementio-
ned into consideration, at the next stage the effect of the
polymorphic variant C-108T of PON1 gene on the risk
of developing BC and HD was evaluated for three age
subgroups of women.
The genotype frequencies for three age subgroups
of women with BC and HD were compared with the
control group. The reliable differences were revealed
only for the women over 54 (Table 3).
Compared to the control, the women with BC of this
age subgroup had remarkable increase in the frequency
of genotype -108CT of PON1 gene (�
2 = 4.01; p < 0.05;
OR = 3.23, 95 % CI: 1.14–9.17), which corresponds to
a lower level of the PON1 activity. On the other hand,
the women over 54 with the genotype -108CC of PON1
gene had almost 4-fold reliably lower risk of developing
BC (�
2 = 4.01; p < 0.05; OR = 0.26, 95 % CI: 0.08–0.87).
Our results have been indirectly confirmed by the re-
sults of the studies, conducted by Stevens et al. and
Antognelli et al., when the postmenopausal women had
genotype 55MM by the polymorphic variant L55M of
PON1 gene, responsible for a lower level of the PON1
activity, and it was associated with the reliably increa-
sing risk of developing BC [9, 10]. Saadat [11] also con-
firmed the fact that the presence of heterozygote 55LM
or homozygote 55MM of PON1 gene was associated
with the increasing risk of developing BC.
Why has this regularity been revealed only for ol-
der women whereas the paraoxonase 1 activity for adults
is known to be constant? The results of recent studies,
however, have shown a progressing decrease in the pa-
raoxonase 1 activity for elderly people, which is related
312
L. Ye. FISHCHUK
Genotype
Study groups
BC, n (%) HD, n (%) Control, n (%)
-108CC 31 (23.66) 28 (21.54)* 34 (33.33)*
-108CT 70 (53.44) 64 (49.23) 48 (47.06)
-108ÒÒ 30 (22.90) 38 (29.23) 20 (19.61)
Note. *p < 0.05.
Table 2
The frequency of genotypes by the polymorphic variant C-108T of
PON1 gene in the study groups
Genotype
Study groups
BC, n (%) HD, n (%) Control, n (%)
18–35 years
-108CC 11 (20.75) 6 (27.27) 10 (30.30)
-108CT 27 (50.94) 8 (36.36) 14 (42.42)
-108ÒÒ 15 (28.30) 8 (36.36) 9 (27.27)
36–54 years
-108CC 16 (30.77) 14 (20.00) 5 (21.74)
-108CT 24 (46.15) 38 (54.29) 13 (56.52)
-108ÒÒ 12 (23.08) 18 (25.71) 5 (21.74)
over 54 years
-108CC 4 (15.38)* 8 (21.05) 19 (41.30)*
-108CT 19 (73.08)* 18 (47.37) 21 (45.65)*
-108ÒÒ 3 (11.54) 12 (31.58) 6 (13.04)
Note. *p < 0.05.
Table 3
The distribution of genotype frequencies by the polymorphic variant
C-108T of PON1 gene in age subgroups of women with BC, HD and
the control group
to the development of the oxidative stress while aging
[12]. Thus, our results may be explained by the fact that
the women of this age become more sensitive to a de-
crease in the paraoxonase 1 activity, which, in its turn,
leads to a lower level of detoxification of carcinogens
and oxidants inducing inflammatory processes.
Conclusions. It is the first study in Ukraine, aimed at
the determination of the associations of the polymor-
phic variant C-108T of PON1 gene with the risk of de-
veloping BC and HD in women. The results of the stu-
dy give grounds for the assumption that the presence of
genotype -108CC of PON1 gene in women is asso-
ciated with an over 1.5-fold decrease in the risk of de-
veloping HD. As for the women over 54, the presence
of genotype -108CC of PON1 gene is associated with
the almost 4-fold decreased risk of developing BC,
whereas the presence of genotype -108CT of PON1 ge-
ne is associated with the over 3-fold increased risk of
developing BC.
Àñîö³àö³ÿ ãåíîòèï³â çà ïîë³ìîðôíèì âàð³àíòîì C-108T
ãåíà PON1 ç ðèçèêîì ðîçâèòêó ðàêó ìîëî÷íî¿ çàëîçè òà
ã³ïåðòîí³÷íî¿ õâîðîáè ó æ³íîê
Ë. ª. Ô³ùóê
Ðåçþìå
Ìåòà. Ïðîàíàë³çóâàòè âïëèâ ïîë³ìîðôíîãî âàð³àíòà C-108T ãå-
íà PON1 íà ðèçèê ðîçâèòêó ðàêó ìîëî÷íî¿ çàëîçè (ÐÌÇ) òà ã³ïåð-
òîí³÷íî¿ õâîðîáè (ÃÕ) ó æ³íîê. Ìåòîäè. Äî äîñë³äæåííÿ çàëó÷å-
íî 130 æ³íîê ç ä³àãíîçîì ÃÕ ²² ñòóïåíÿ ç íåóñêëàäíåíèì ïåðåá³ãîì
òà 131 æ³íêó ç ä³àãíîçîì ÐÌÇ I ³ ²² ñòàä³é áåç ñåðöåâî-ñóäèííèõ
óñêëàäíåíü. Äî êîíòðîëüíî¿ ãðóïè óâ³éøëè 102 æ³íêè áåç ñåðöåâî-
ñóäèííî¿ òà îíêîëîã³÷íî¿ ïàòîëîã³é. Äëÿ ìîëåêóëÿðíî-ãåíåòè÷íî-
ãî àíàë³çó âèêîðèñòàíî ÄÍÊ, âèä³ëåíó ç ëåéêîöèò³â ïåðèôåð³éíî¿
êðîâ³. Ãåíîòèïóâàííÿ çà ïîë³ìîðôíèì âàð³àíòîì C-108T ãåíà
PON1 ïðîâîäèëè ³ç çàñòîñóâàííÿì ìåòîäó ÏËÐ-ÏÄÐÔ. Ðåçóëü-
òàòè. Âñòàíîâëåíî, ùî íàÿâí³ñòü ãåíîòèïó -108CC ãåíà PON1 ó
æ³íîê àñîö³éîâàíà ç³ çíèæåííÿì ðèçèêó ðîçâèòêó ÃÕ á³ëüø í³æ ó
1,5 ðàçó. Äëÿ æ³íîê, ñòàðøèõ 54 ðîê³â, íàÿâí³ñòü ãåíîòèïó -108CC
ãåíà PON1 àñîö³éîâàíà ³ç çìåíøåííÿì ðèçèêó ðîçâèòêó ÐÌÇ ìàé-
æå ó 4 ðàçè, à íàÿâí³ñòü ãåíîòèïó -108CT ãåíà PON1, íàâïàêè, ïî-
â’ÿçàíà ç³ çðîñòàííÿì ðèçèêó ðîçâèòêó ÐÌÇ á³ëüø í³æ ó 3 ðàçè.
Âèñíîâêè. Ïîë³ìîðôíèé âàð³àíò C-108T ãåíà PON1 º ìîæëèâèì
ïðîãíîñòè÷íèì ìàðêåðîì ðèçèêó ðîçâèòêó ÐÌÇ òà ÃÕ ó æ³íîê.
Êëþ÷îâ³ ñëîâà: ãåí, PON1, ðàê ìîëî÷íî¿ çàëîçè, ã³ïåðòîí³÷íà
õâîðîáà.
Àññîöèàöèÿ ãåíîòèïîâ ïîëèìîðôíîãî âàðèàíòà C-108T
ãåíà PON1 ñ ðèñêîì ðàçâèòèÿ ðàêà ìîëî÷íîé æåëåçû è
ãèïåðòîíè÷åñêîé áîëåçíè ó æåíùèí
Ë. Å. Ôèùóê
Ðåçþìå
Öåëü. Ïðîàíàëèçèðîâàòü âëèÿíèå ïîëèìîðôíîãî âàðèàíòà C-108T
ãåíà PON1 íà ðèñê ðàçâèòèÿ ðàêà ìîëî÷íîé æåëåçû (ÐÌÆ) è ãè-
ïåðòîíè÷åñêîé áîëåçíè (ÃÁ) ó æåíùèí. Ìåòîäû.  èññëåäîâàíèè
ó÷àñòâîâàëè 130 æåíùèí ñ äèàãíîçîì ÃÁ II ñòåïåíè ñ íåîñëîæ-
íåííûì òå÷åíèåì è 131 æåíùèíà ñ äèàãíîçîì ÐÌÆ I è II ñòàäèé
áåç ñåðäå÷íî-ñîñóäèñòûõ îñëîæíåíèé. Êîíòðîëüíóþ ãðóïïó ñî-
ñòàâèëè 102 æåíùèíû áåç ñåðäå÷íî-ñîñóäèñòîé è îíêîëîãè÷åñ-
êîé ïàòîëîãèé. Äëÿ ìîëåêóëÿðíî-ãåíåòè÷åñêîãî àíàëèçà èñïîëüçî-
âàëè ÄÍÊ, âûäåëåííóþ èç ëåéêîöèòîâ ïåðèôåðè÷åñêîé êðîâè. Ãå-
íîòèïèðîâàíèå ïî ïîëèìîðôíîìó âàðèàíòó C-108T ãåíà PON1
ïðîâîäèëè ñ ïðèìåíåíèåì ìåòîäà ÏÖÐ-ÏÄÐÔ. Ðåçóëüòàòû. Âû-
ÿâëåíî, ÷òî íàëè÷èå ãåíîòèïà -108CC ãåíà PON1 ó æåíùèí àññî-
öèèðîâàíî ñî ñíèæåíèåì ðèñêà ðàçâèòèÿ ÃÁ áîëåå ÷åì â 1,5 ðàçà.
Äëÿ æåíùèí ñòàðøå 54 ëåò íàëè÷èå ãåíîòèïà -108CC ãåíà PON1
àññîöèèðîâàíî ñî ñíèæåíèåì ðèñêà ðàçâèòèÿ ÐÌÆ ïî÷òè â 4 ðà-
çà, à íàëè÷èå ãåíîòèïà -108CT ãåíà PON1, íàîáîðîò, ñâÿçàíî ñ
âîçðàñòàíèåì ðèñêà ðàçâèòèÿ ÐÌÆ áîëåå ÷åì â 3 ðàçà. Âûâîäû.
Ïîëèìîðôíûé âàðèàíò C-108T ãåíà PON1 ÿâëÿåòñÿ âîçìîæíûì
ïðîãíîñòè÷åñêèì ìàðêåðîì ðèñêà ðàçâèòèÿ ÐÌÆ è ÃÁ ó æåíùèí.
Êëþ÷åâûå ñëîâà: ãåí, PON1, ðàê ìîëî÷íîé æåëåçû, ãèïåðòîíè-
÷åñêàÿ áîëåçíü.
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Received 01.04.14
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