Study on occurrence of the IVS8-5T allele of the CFTR gene in Ukrainian males with spermatogenesis failure
Aim. To study the IVS8-5T allele of the CFTR gene and it is involvement in spermatogenesis failure in men with azoospermia and oligozoospermia. Methods. The IVS8-nT polymorphism was analyzed by PCR followed by «A.L.F.-express» fragment analysis in the infertile men group, consisting of 113 azoosperm...
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nasplib_isofts_kiev_ua-123456789-1541332025-02-23T18:27:50Z Study on occurrence of the IVS8-5T allele of the CFTR gene in Ukrainian males with spermatogenesis failure Дослідження частоти алеля IVS8-5T гена CFTR в українських чоловіків із порушенням сперматогенезу Исследование частоты аллеля IVS8-5T гена CFTR у украинских мужчин с нарушением сперматогенеза Fesai, O.A. Kravchenko, S.A. Zinchenko, V.M. Livshits, L.A. Biomedicine Aim. To study the IVS8-5T allele of the CFTR gene and it is involvement in spermatogenesis failure in men with azoospermia and oligozoospermia. Methods. The IVS8-nT polymorphism was analyzed by PCR followed by «A.L.F.-express» fragment analysis in the infertile men group, consisting of 113 azoospermic and 217 oligozoospermic patients, and the control group of 150 fertile men with proven paternity. Results. The frequency of the IVS8-5T allele among infertile males was higher than in controls. A statistically significant difference (P < 0.05) was observed in the frequencies of the IVS8-5T allele in azoospermia patients (5.3 %) when compared with the control group (2.0 %). Conclusions. The IVS8-5T allele of the CFTR gene contributes to spermatogenesis failure and/or sperm maturation. Мета. Дослідити алель IVS8-5T гена CFTR і його залучення до порушенням сперматогенезу у чоловіків із азооспермією та олігозооспермією. Методи. IVS8-nT-поліморфізм аналізували у групі безплідних чоловіків, яку склали 113 пацієнтів із азоо- спермією та 217 пацієнтів із олігозооспермією, та в контрольній групі, до якої увійшли 150 фертильних чоловіків із підтвердженим батьківством, з використанням ПЛР та фрагментного аналізу «A.L.F.-express». Результати. Частота появи алеля IVS8-5T серед безплідних чоловіків була вищою, ніж у контролі. Статистично достовірну різницю (P < 0,05) визначено за частотами IVS8-5T-алеля у пацієнтів із азооспермією (5,3 %) порівняно з контрольною групою (2,0 %). Висновки. Алель IVS8-5T гена CFTR сприяє порушенню сперматогенезу і/або дозріванню сперматозоїдів. Цель. Изучение аллеля IVS8-5T гена CFTR и его вовлечение в нарушение сперматогенеза у мужчин с азооспермией и олигозооспермией. Методы. IVS8-nT-полиморфизм исследовали в группе бесплодных мужчин, которую составили 113 пациентов с азооспермией и 217 пациентов с олигозооспермией, и контрольной группе, куда вошли 150 фертильных мужчин с подтвержденным отцовством, с использованием ПЦР и фрагментного анализа с «A.L.F.-express». Результаты. Частота появления IVS8-5T-аллеля среди бесплодных мужчин была выше, чем в контроле. Статистически достоверная разница (P < 0,05) определена по частоте IVS8-5T-аллеля у пациентов с азооспермией (5,3 %) по сравнению с контрольной группой (2,0 %). Выводы. IVS8-5T-аллель гена CFTR способствует нарушению сперматогенеза и/или дозреванию сперматозоидов. 2010 Article Study on occurrence of the IVS8-5T allele of the CFTR gene in Ukrainian males with spermatogenesis failure / O.A. Fesai, S.A. Kravchenko, V.M. Zinchenko, L.A. Livshits // Вiopolymers and Cell. — 2010. — Т. 26, № 4. — С. 306-310. — англ. 0233-7657 DOI: http://dx.doi.org/10.7124/bc.000164 https://nasplib.isofts.kiev.ua/handle/123456789/154133 575.11 + 577.21 + 616.697 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 Fesai, O.A. Kravchenko, S.A. Zinchenko, V.M. Livshits, L.A. Study on occurrence of the IVS8-5T allele of the CFTR gene in Ukrainian males with spermatogenesis failure Вiopolymers and Cell |
| description |
Aim. To study the IVS8-5T allele of the CFTR gene and it is involvement in spermatogenesis failure in men with azoospermia and oligozoospermia. Methods. The IVS8-nT polymorphism was analyzed by PCR followed by «A.L.F.-express» fragment analysis in the infertile men group, consisting of 113 azoospermic and 217 oligozoospermic patients, and the control group of 150 fertile men with proven paternity. Results. The frequency of the IVS8-5T allele among infertile males was higher than in controls. A statistically significant difference (P < 0.05) was observed in the frequencies of the IVS8-5T allele in azoospermia patients (5.3 %) when compared with the control group (2.0 %). Conclusions. The IVS8-5T allele of the CFTR gene contributes to spermatogenesis failure and/or sperm maturation. |
| format |
Article |
| author |
Fesai, O.A. Kravchenko, S.A. Zinchenko, V.M. Livshits, L.A. |
| author_facet |
Fesai, O.A. Kravchenko, S.A. Zinchenko, V.M. Livshits, L.A. |
| author_sort |
Fesai, O.A. |
| title |
Study on occurrence of the IVS8-5T allele of the CFTR gene in Ukrainian males with spermatogenesis failure |
| title_short |
Study on occurrence of the IVS8-5T allele of the CFTR gene in Ukrainian males with spermatogenesis failure |
| title_full |
Study on occurrence of the IVS8-5T allele of the CFTR gene in Ukrainian males with spermatogenesis failure |
| title_fullStr |
Study on occurrence of the IVS8-5T allele of the CFTR gene in Ukrainian males with spermatogenesis failure |
| title_full_unstemmed |
Study on occurrence of the IVS8-5T allele of the CFTR gene in Ukrainian males with spermatogenesis failure |
| title_sort |
study on occurrence of the ivs8-5t allele of the cftr gene in ukrainian males with spermatogenesis failure |
| publisher |
Інститут молекулярної біології і генетики НАН України |
| publishDate |
2010 |
| topic_facet |
Biomedicine |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/154133 |
| citation_txt |
Study on occurrence of the IVS8-5T allele of the CFTR gene in Ukrainian males with spermatogenesis failure / O.A. Fesai, S.A. Kravchenko, V.M. Zinchenko, L.A. Livshits // Вiopolymers and Cell. — 2010. — Т. 26, № 4. — С. 306-310. — англ. |
| series |
Вiopolymers and Cell |
| work_keys_str_mv |
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2025-11-24T10:29:21Z |
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2025-11-24T10:29:21Z |
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| fulltext |
Study on occurrence of the IVS8-5T allele of the CFTR
gene in Ukrainian males with spermatogenesis failure
O. A. Fesai, S. A. Kravchenko, V. M. Zinchenko1, L. A. Livshits
Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine
150, Akademika Zabolotnogo str., Kyiv, Ukraine, 03680
1Clinic «ISIDA-IVF»65, Ivana Lepse boulevard, Kyiv, Ukraine, 03126
olga_fesay@ukr.net
Aim. To study the IVS8-5T allele of the CFTR gene and it is involvement in spermatogenesis failure in men
with azoospermia and oligozoospermia. Methods. The IVS8-nT polymorphism was analyzed by PCR
followed by «A.L.F.-express» fragment analysis in the infertile men group, consisting of 113 azoospermic
and 217 oligozoospermic patients, and the control group of 150 fertile men with proven paternity. Results.
The frequency of the IVS8-5T allele among infertile males was higher than in controls. A statistically
significant difference (P < 0.05) was observed in the frequencies of the IVS8-5T allele in azoospermia
patients (5.3 %) when compared with the control group (2.0 %). Conclusions. The IVS8-5T allele of the
CFTR gene contributes to spermatogenesis failure and/or sperm maturation.
Keywords: male infertility, spermatogenesis failure, IVS8-nT polymorphism.
Introduction. Many genes are likely to be involved in
the complex process of reproduction [1]. The main
genetic causes of male infertility are microdeletions in
the Y chromosome (AZF region) connected with oligo-
zoospermia or azoospermia. Infertility, or at least
subfertility, in males with Cystic Fibrosis (CF) was
first suspected in the 1960s. Abnormalities in semen
parameters have also been identified in males with CF
and CBAVD (congenital bilateral absence of the vas
deferens) [2]. It were suggested that the frequency of
CFTR (cystic fibrosis transmembrane conductance
regulator) gene mutations in infertile males was signi-
ficantly higher than the expected CF carrier frequency
in the general population [3].
The CFTR gene contains 27 exons encompassing
~180 kb of DNA on chromosome band 7q31.2. The
CFTR gene encodes a transmembrane protein that
forms a cAMP-regulated chloride channel. It is expres-
sed in epithelial cells of exocrine tissues, such as the
lungs, pancreas, epididymal glands, vas deferens and
seminal vesicles [4]. Three length variations of a poly-
thymidine tract within the splice acceptor site in the
introne 8 of the CFTR gene (GenBank accession no.
M55106) have been associated with variable efficiency
of the exon 9 splicing [5].
The most frequent CFTR mutation conferring a
mild phenotype found in CBAVD patients is the
IVS8-5T allele [6]. IVS8-5T is one of the alleles found
at the polymorphic nT locus in the intron 8 of the CFTR
gene. A stretch of 5, 7, or 9 thymidine residues is found
at this locus. Less efficient splicing occurs when a lo-
wer number of thymidines are present, resulting in the
CFTR transcripts that lack the exon 9 sequences [7].
Alternatively, the spliced CFTR transcripts lacking
the exon 9 sequences are found in any individual, but
the extent varies depending on the alleles present at the
306
ISSN 0233-7657. Biopolymers and Cell. 2010. Vol. 26. N 4
Ó Institute of Molecular Biology and Genetics NAS of Ukraine, 2010
nT locus. In individuals homozygous for the IVS8-5T
allele up to 90 % of the CFTR transcripts lack the exon
9 [7]. It has been shown that the CFTR transcripts la-
cking the exon 9 sequences result in the CFTR proteins
that do not mature [8, 9]. The IVS8-5T variant pro-
duces a lower level of the normal CFTR mRNA trans-
cripts than the 7T and 9T alleles and is associated with
disseminated bronchiectasis, CBAVD and epididymal
obstruction [7]. In addition to the classic CFTR muta-
tions, up to 40 % of CBAVD patients show the IVS8-
5T allele, that is five thymidines tract within the intron
8 [6, 10, 11], which results in a reduction of the CFTR
gene splicing efficacy [7].
The aim of this study was to establish the as-
sociation between the IVS8-5T allele and defects of
spermatogenesis. For this we analyzed the IVS8-nT
CFTR gene polymorphism in infertile men.
Materials and methods. The analysis of the
IVS8-nT polymorphism of the CFTR gene was per-
formed in 330 infertile men from Ukraine (113 with
azoospermia – no sperm found in the ejaculate even
after centrifugation and 217 with oligozoospermia –
sperm count < 20 million/ml). All patients from
«ISIDA-IVF», «NADIJA» clinics and Institute of Ge-
netics and Reproduction were involved in ICSI
(intracytoplasmic sperm injection) program. The con-
trol group consisted of 150 fertile men of proven fer-
tility (have fathered at least one child each, paternity
being proven). Blood samples (5 ml) from both infer-
tile and fertile men were collected after their informed
written consent.
DNA was extracted out from the peripheral blood
leukocytes by standard phenol-chloroform extraction
methods using proteinase K («Fermentas», Lithuania)
[12]. For DNA extraction and purification we used ep-
pendorf centrifuge 5415C («Eppendorf», Germany).
The CFTR mutation analysis was performed for 6
mutations: delF508, CFTRdele2,3 (21kb), N1303K,
R117H, 1677delTA and 621 + 1G–T as previously
described [13].
For the IVS8-nT polymorphism the PCR amplifi-
cation was performed with specific oligonucleotide
primers, as described by Chillon M. et al. [6]. The PCR
reaction was performed in a final volume of 25 ml
containing 1 ́ PCR buffer, 1.5 mM MgCl2, 200 ìM of
each dNTP, 1 mM of each primer, 0.2 units of Taq-DNA
polymerase («Fermentas», Lithuania) and 200 ng of the
DNA template.
The cycling conditions for the IVS8-nT polymor-
phism were as follows: initial denaturation at 96 °C for
4 min up to 5 cycles, consisting of denaturation at 96 °C
for 40 s, annealing at 66 °C for 40 s, extension at 72 °C
for 1 min 50 s, up to 23 cycles, consisting of dena-
turation at 95 °C for 30 s, annealing at 64 °C for 40 s,
extension at 70 °C for 1min 30 s, and final elongation
step at 72 °C for 3 min. For these experiments Applied
Biosystems GeneAmp PCR system 2720 Termal Cyc-
ler («Applied Biosystems», USA) was used. Electro-
phoresis of the PCR products was performed in 1.8 %
agarose gel.
For fragment analysis of the IVS8-nT polymor-
phism in an automated laser fluorometer «A.L.F.-exp-
ress» («Amersham Pharmacia Biotech», Sweden) the
Cy5-labeled PCR products were used. The PCR frag-
ment analysis was performed using the Fragment Ma-
nager Computer program (Fragment Manager Softwa-
re V2.1, «Amersham Pharmacia Biotech») (Fig. 1).
The statistical analysis was performed using
Genepop software [14]. Differences were considered
significant at P < 0.05 value of Fisher exact test.
Results and discussion. Genotypes and allele fre-
quencies of the IVS-nT polymorphism analyzed
among 330 infertile men are presented in Table.
In the patients’ group of we have found 21 indivi-
duals with the IVS8-5T allele in compound heterozy-
gosity with the IVS8-7T and IVS8-9T alleles. Two pa-
tients were identified as homozygous for the IVS8-5T
allele. In the control group we have found 4 individuals
with the IVS8-5T allele in compound heterozygosity
with the IVS8-7T and IVS8-9T alleles. One patient was
identified as homozygous for the IVS8-5T allele.
It is important to note that genotypes which inclu-
ded the IVS8-5T allele were significantly prevalent
(P < 0.01) in patients with azoospermia (9.7 %) com-
pared to the control group (3.3 %) (OR = 3.128, 95 %
CI 1.055–9.275). The frequency of the IVS8-5T allele
among infertile males was 3.8 %, 1.9-fold higher than
in the controls (2.0 %). A statistically significant diffe-
rence (P < 0.05) was observed in the frequency of the
IVS8-5T allele in azoospermia patients (5.3 %) when
compared with the control group (2.0 %) (OR = 2.748,
95 % CI 1.015–7.437).
307
STUDY ON OCCURRENCE OF THE IVS8-5T ALLELE OF THE CFTR GENE
This increased IVS8-5T allele frequency in men
with azoospermia suggests that the CFTR protein could
be involved in the process of spermatogenesis or sperm
maturation. It could also play a crucial role in the deve-
lopment of the epididymis glands and the vas deferens
[15].
The IVS8-5T allele is known to give rise to an aber-
rantly spliced mRNA that mostly lacks the exon 9.
Such anomalous mRNA is translated into the abnormal
CFTR protein which cannot function as a Cl– channel.
Therefore, men with the IVS8-5T variant in the non-
coding region of the gene would produce low level of
normal CFTR protein in the epididymis, especially in
homozygous mutant individuals [16]. Chillon showed
that the IVS8-5T allele was significantly more frequent
in the chromosomes of patients with CBAVD than in
the European general population [6].
In our study the proportion of the men with azo-
ospermia (part of which may have undiagnosed
CBAVD) who had the IVS8-5T allele (9.7 %) was
higher than that in the European general population
(5.2 %), and in our control group (3.3 %). Appro-
ximately the same percentage of the IVS8-5T allele
carriers was found in the men with CBAVD from dif-
ferent countries [17].
Also, it has been shown that mutations of the CFTR
gene expressed in the proximal epididymis can lead to
agenesis of the distal epididymis and vas deferens [18].
The results of CFTR gene mutation analysis per-
formed in the group of infertile males (n = 330) show
that the delF508 mutation was found in 16 patients
(4.8 %), CFTRdele2,3 (21 kb) in 2 patients (0.6 %) and
R117H in 1 patient (0.3 %). It is important to note that
the R117H mutation was not found either in the general
population or in the group of CF patients from Ukraine
[13]. Therefore, the frequency of CFTR gene mutation
carriers in the azoospermia group (n = 113) was 10.6 %.
The frequency of CFTR gene mutation carriers in the
infertile men (n = 330) was 5.8 %. In our previous study
we showed that the total frequency of the CFTR gene
mutations in Ukrainian population (n = 621) was
0.97 % [13]. It is significantly lower (P < 0.01) than in
the group of men with spermatogenesis failure (n =
= 330).
It has been shown that the compound heterozygotes
for the IVS8-5T allele and other CFTR mutation dis-
play a variable phenotype, ranging from normal to ma-
le infertility or nonclassic CF [17]. For example, when
the IVS8-5T allele is found in the compound hete-
rozygosity with a severe CFTR mutation, or even the
IVS8-5T allele, the pathology such as CBAVD was
observed. The IVS8-5T allele, in combination with a
308
FESAI O. A. ET AL.
180 190 200 210 220 bp
1
2
3
4
5
6
Fig. 1. An example of analysis of the IVS8-nT polymorphism with
the use of «A.L.F.-express». Genotypes: 1 – 5T/5T; 2 – 7T/9T; 3 –
5T/7T; 4 – 5T/9T; 5 – 7T/7T; 6 – 9T/9T
Azoospermia
group, n (%)
Oligozoospermia
group n (%)
Infertile
group n (%)
Control
group n (%)
Genotype
5T/5T 1 (0.9) 1 (0.5) 2 (0.6) 1 (0.7)
5T/7T 5 (4.4) 10 (4.6) 15 (4.6) 3 (2.0)
5T/9T 5 (4.4) 1 (0.5) 6 (1.8) 1 (0.7)
7T/7T 81 (71.7) 161 (74.2)
242
(73.3)
125 (83.3)
7T/9T 16 (14.2) 39 (17.9) 55 (16.7) 12 (8.0)
9T/9T 5 (4.4) 5 (2.3) 10 (3.0) 8 (5.3)
Allele
5T 12 (5.3) 13 (2.9) 25 (3.8) 6 (2.0)
7T
183
(80.9)
371 (85.5)
554
(83.9)
265 (88.3)
9T 31 (13.7) 50 (11.5) 81 (12.3) 29 (9.7)
Genotype and allele distribution among the infertile and control
groups
Azoospermia group, n = 113; oligozoospermia group (n = 217);
infertile group (n = 330); control group (n = 150)
single mutation in the other chromosome, is common in
CBAVD and accounts for the observed Wolffian duct
abnormalities [19].
However, not all males who are compound he-
terozygous for the severe CFTR mutation and IVS8-5T
allele develop CBAVD. In our study four patients
(1.2 %) with azoospermia and oligozoospermia have
the CFTR mutation in combination with the 5T/7T and
5T/9T genotypes. Therefore, the results of this study
confirm that the IVS8-5T allele can be classified as a
disease mutation with partial penetrance [20] and a
high risk genetic variant for male infertility. This
suggesting is quite possible since the level of the CFTR
gene expression is very high in the cells from different
departments of male genital.
Conclusions. The prevalence of the IVS8-5T allele
(P < 0.05) and the CFTR mutation in males with
azoospermia, suggests that the CFTR protein may play
a crucial role in the spermatogenesis and/or sperm ma-
turation, independently of its functioning in the deve-
lopment of epithelial ducts such as the vas deferens.
Acknowledgements. We thank the staff at the cli-
nic «ISIDA-IVF», clinic «NADIJA» and Institute of
Genetics and Reproduction for their kind assistance in
collecting the blood samples.
Î. À. Ôå ñàé, Ñ. À. Êðàâ ÷åí êî, Â. Ì. dzí÷åí êî, Ë. À. ˳âøèöü
Äîñë³äæåí íÿ ÷àñ òî òè àëå ëÿ IVS8-5T ãåíà CFTR â óêð à¿íñüêèõ
÷î ëîâ³ê³â ³ç ïî ðó øåí íÿì ñïåð ìà òî ãå íåçó
Ðå çþ ìå
Ìåòà. Äîñë³äèòè àëåëü IVS8-5T ãåíà CFTR ³ éîãî çà ëó ÷åí íÿ äî
ïî ðó øåí íÿì ñïåð ìà òî ãå íåçó ó ÷î ëîâ³ê³â ³ç àçî îñ ïåð쳺þ òà
îë³ãî çî îñ ïåð쳺þ. Ìå òî äè. IVS8-nT-ïîë³ìîðô³çì àíàë³çóâàëè ó
ãðóï³ áåçïë³äíèõ ÷î ëîâ³ê³â, ÿêó ñêëà ëè 113 ïàö³ºíò³â ³ç àçîî-
ñïåð쳺þ òà 217 ïàö³ºíò³â ³ç îë³ãî çî îñ ïåð쳺þ, òà â êîí -
òðîëüí³é ãðóï³, äî ÿêî¿ óâ³éøëè 150 ôåð òèëü íèõ ÷î ëîâ³ê³â ³ç
ï³äòâåð äæå íèì áàòüê³âñòâîì, ç âè êî ðèñ òàí íÿì ÏËÐ òà
ôðàã ìåí òíî ãî àíàë³çó «A..L.F.-express». Ðå çóëü òà òè. ×àñ òî -
òà ïîÿâè àëå ëÿ IVS8-5T ñå ðåä áåçïë³äíèõ ÷î ëîâ³ê³â áóëà âè ùîþ,
í³æ ó êîí òðîë³. Ñòà òèñ òè÷ íî äîñ òîâ³ðíó ð³çíè öþ (P < 0,05)
âèç íà ÷å íî çà ÷àñ òî òà ìè IVS8-5T-àëå ëÿ ó ïàö³ºíò³â ³ç àçîî-
ñïåð쳺þ (5,3 %) ïîð³âíÿ íî ç êîí òðîëü íîþ ãðó ïîþ (2,0 %). Âèñ -
íîâ êè. Àëåëü IVS8-5T ãåíà CFTR ñïðèÿº ïî ðó øåí íþ ñïåð ìà òî -
ãå íå çó ³/àáî äîçð³âàí íþ ñïåð ìà òî çî¿ä³â.
Êëþ ÷îâ³ ñëî âà: ÷î ëîâ³÷å áåçïë³ääÿ, ïî ðó øåí íÿ ñïåð ìà òî ãå -
íåçó, IVS8-nT-ïîë³ìîðô³çì.
Î. À. Ôå ñàé, Ñ. À. Êðàâ ÷åí êî, Â. Ì. Çèí ÷åí êî, Ë. À. Ëèâ øèö
Èññëå äî âà íèå ÷àñ òî òû àë ëå ëÿ IVS8-5T ãåíà CFTR ó óêðà èí ñêèõ
ìóæ ÷èí ñ íà ðó øå íè åì ñïåð ìà òî ãå íå çà
Ðå çþ ìå
Öåëü. Èçó ÷å íèå àë ëå ëÿ IVS8-5T ãåíà CFTR è åãî âîâ ëå ÷å íèå â íà -
ðó øå íèå ñïåð ìà òî ãå íå çà ó ìóæ ÷èí ñ àçî îñ ïåð ìè åé è îëè ãî çî -
îñ ïåð ìè åé. Ìå òî äû. IVS8-nT-ïî ëè ìîð ôèçì èñ ñëå äî âàëè â
ãðóï ïå áåñ ïëîä íûõ ìóæ ÷èí, êî òî ðóþ ñî ñòà âè ëè 113 ïà öè åí -
òîâ ñ àçî îñ ïåð ìè åé è 217 ïà öè åí òîâ ñ îëè ãî çî îñ ïåð ìè åé, è êîí -
òðîëü íîé ãðóï ïå, êóäà âîø ëè 150 ôåð òèëü íûõ ìóæ ÷èí ñ
ïîä òâåð æäåí íûì îò öî âñòâîì, ñ èñ ïîëü çî âà íè åì ÏÖÐ è ôðàã -
ìåí òíî ãî àíà ëè çà ñ «A.L.F.-express». Ðå çóëü òà òû. ×àñ òî òà
ïî ÿâ ëå íèÿ IVS8-5T-àë ëå ëÿ ñðå äè áåñ ïëîä íûõ ìóæ ÷èí áûëà
âûøå, ÷åì â êîí òðî ëå. Ñòà òèñ òè ÷åñ êè äîñ òî âåð íàÿ ðàç íè öà
(P < 0,05) îïðå äå ëå íà ïî ÷àñ òî òå IVS8-5T-àë ëå ëÿ ó ïà öè åí òîâ ñ
àçî îñ ïåð ìè åé (5,3 %) ïî ñðàâ íå íèþ ñ êîí òðîëü íîé ãðóï ïîé
(2,0 %). Âû âî äû. IVS8-5T-àë ëåëü ãåíà CFTR ñïî ñî áñòâó åò íà -
ðó øå íèþ ñïåð ìà òî ãå íå çà è/èëè äîç ðå âà íèþ ñïåð ìà òî çî è äîâ.
Êëþ ÷å âûå ñëî âà: ìóæ ñêîå áåñ ïëî äèå, íà ðó øå íèå ñïåð ìà òî -
ãå íå çà, IVS8-nT-ïî ëè ìîð ôèçì.
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UDC 575.11 + 577.21 + 616.697
Recieved 01.04.10
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