Study on the IFNL4 gene ss469415590 variant in Ukrainian population
Aim. To determine genotype and allele disribution for the IFNL4 gene ss469415590 and examine it for linkage with the IL28B gene rs12979860 in Ukrainian population. Methods. The studied group consisted of 100 unrelated donors of Eastern European origin representing the population of Ukraine. Genotypi...
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Інститут молекулярної біології і генетики НАН України
2014
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| Назва видання: | Вiopolymers and Cell |
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| Цитувати: | Study on the IFNL4 gene ss469415590 variant in Ukrainian population / A.M. Kucherenko, V.M. Pampukha, L.A. Livshits // Вiopolymers and Cell. — 2014. — Т. 30, № 5. — С. 400-402. — Бібліогр.: 7 назв. — англ. |
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irk-123456789-1545232019-06-16T01:32:46Z Study on the IFNL4 gene ss469415590 variant in Ukrainian population Kucherenko, A.M. Pampukha, V.M. Livshits, L.A. Short Communications Aim. To determine genotype and allele disribution for the IFNL4 gene ss469415590 and examine it for linkage with the IL28B gene rs12979860 in Ukrainian population. Methods. The studied group consisted of 100 unrelated donors of Eastern European origin representing the population of Ukraine. Genotyping for the IFNL4 gene ss469415590 was performed using the amplification-refractory mutation system PCR. Genotyping for the IL28B gene rs12979860 was performed by the PCR-based restriction fragment length polymorphism assay. Results. Genotype frequencies for both studied variants showed no significant deviation from those expected according to Hardy-Weinberg equilibrium. Allelic distribution for ss469415590 was: TT – 0.665, G – 0.335. Allelic frequencies of rs12979860 were: C – 0.655, T – 0.345. The results of likelihood ratio test indicated a linkage disequilibrium between the studied variants (p > 0.0001), the major alleles ss469415590 TT and rs12979860 C were in phase. The genetic structure of Ukrainian population in terms of two studied polymorphic variants is similar to the European population presented in the «1000 genomes» project. Conclusions. Considering a tight linkage revealed in Ukrainian population between the ss469415590 variant and rs12979860, a crucial genetic marker of chronic hepatitis C treatment efficiency, this polymorphism might be a promising target for further investigation as a pharmacogenetic marker. Мета. Встановити розподіл генотипів і алелів за варіантом ss469415590 гена IFNL4, а також дослідити його зчеплення з rs12979860 у гені IL28B в популяції України. Методи. До групи дослідження входили 100 неспоріднених донорів східно-європейського походження, які представляють популяцию України. Варіант ss469415590 гена IFNL4 генотипували методом алель-специфічної ПЛР, варіант rs12979860 гена IL28B – методом ПЛР з подальшим аналізом поліморфізму довжини рестрикційних фрагментів. Результати. Частоти генотипів за обома дослідженими варіантами відповідали очікуваними за рівновагою Харді- Вайнберга. Розподіл частот алелей для ss469415590 було наступним: TT – 0,665, G – 0,335; для rs12979860 – C – 0,655, T – 0,345. Результати тесту співвідношення правдоподібності засвідчують нерівновагу за зчепленням між дослідженими поліморфізмами (p > 0.0001), мажорні алелі ss469415590 TT та rs12979860 C перебувають у фазі. Генетична структура популяції України за двома дослідженими поліморфними варіантами подібна до європейської популяції, описаної в проекті «1000 геномів». Висновки. Беручи до уваги тісне зчеплення між варіантом ss469415590 і важливим генетичним маркером ефективності терапії хронічного гепатиту С у популяції України – rs12979860, цей поліморфізм видається перспективним для подальшого дослідження його як фармакогенетичного маркера. Цель. Установить распределение генотипов и аллелей по варианту ss469415590 гена IFNL4, а также исследовать его сцепление с rs12979860 в гене IL28B в популяции Украины. Методы. В группу исследования входили 100 неродственных доноров восточно-европейского происхождения, представляющие популяцию Украины. Вариант ss469415590 гена IFNL4 генотипировали методом аллель-специфической ПЦР, вариант rs12979860 гена IL28B – ПЦР с последующим анализом полиморфизма длины рестрикционных фрагментов. Результаты. Частоты генотипов по обоим исследуемым вариантами отвечали ожидаемыми по равновесию Харди-Вайнберга. Распределение частот аллелей для ss469415590 было следующим: TT – 0,665, G – 0,335, для rs12979860: C – 0,655, T – 0,345. Результаты теста соотношения правдоподобия указывают на неравновесие по сцеплению между исследуемыми полиморфизмами (p > 0,0001), мажорные аллели ss469415590 TT и rs12979860 C находятся в фазе. Генетическая структура популяции Украины по двум исследованным полиморфным вариантам подобна европейской популяции, описанной в проекте «1000 геномов». Выводы. С учетом тесного сцепления между вариантом ss469415590 и важным генетическим маркером эффективности терапии хронического гепатита С в популяции Украины – rs12979860, этот полиморфизм кажется перспективным для дальнейшего исследования его в качестве фармакогенетического маркера. 2014 Article Study on the IFNL4 gene ss469415590 variant in Ukrainian population / A.M. Kucherenko, V.M. Pampukha, L.A. Livshits // Вiopolymers and Cell. — 2014. — Т. 30, № 5. — С. 400-402. — Бібліогр.: 7 назв. — англ. 0233-7657 DOI: http://dx.doi.org/10.7124/bc.0008B8 http://dspace.nbuv.gov.ua/handle/123456789/154523 575 + 575.111 + 575.22 + 577.13 en Вiopolymers and Cell Інститут молекулярної біології і генетики НАН України |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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DSpace DC |
| language |
English |
| topic |
Short Communications Short Communications |
| spellingShingle |
Short Communications Short Communications Kucherenko, A.M. Pampukha, V.M. Livshits, L.A. Study on the IFNL4 gene ss469415590 variant in Ukrainian population Вiopolymers and Cell |
| description |
Aim. To determine genotype and allele disribution for the IFNL4 gene ss469415590 and examine it for linkage with the IL28B gene rs12979860 in Ukrainian population. Methods. The studied group consisted of 100 unrelated donors of Eastern European origin representing the population of Ukraine. Genotyping for the IFNL4 gene ss469415590 was performed using the amplification-refractory mutation system PCR. Genotyping for the IL28B gene rs12979860 was performed by the PCR-based restriction fragment length polymorphism assay. Results. Genotype frequencies for both studied variants showed no significant deviation from those expected according to Hardy-Weinberg equilibrium. Allelic distribution for ss469415590 was: TT – 0.665, G – 0.335. Allelic frequencies of rs12979860 were: C – 0.655, T – 0.345. The results of likelihood ratio test indicated a linkage disequilibrium between the studied variants (p > 0.0001), the major alleles ss469415590 TT and rs12979860 C were in phase. The genetic structure of Ukrainian population in terms of two studied polymorphic variants is similar to the European population presented in the «1000 genomes» project. Conclusions. Considering a tight linkage revealed in Ukrainian population between the ss469415590 variant and rs12979860, a crucial genetic marker of chronic hepatitis C treatment efficiency, this polymorphism might be a promising target for further investigation as a pharmacogenetic marker. |
| format |
Article |
| author |
Kucherenko, A.M. Pampukha, V.M. Livshits, L.A. |
| author_facet |
Kucherenko, A.M. Pampukha, V.M. Livshits, L.A. |
| author_sort |
Kucherenko, A.M. |
| title |
Study on the IFNL4 gene ss469415590 variant in Ukrainian population |
| title_short |
Study on the IFNL4 gene ss469415590 variant in Ukrainian population |
| title_full |
Study on the IFNL4 gene ss469415590 variant in Ukrainian population |
| title_fullStr |
Study on the IFNL4 gene ss469415590 variant in Ukrainian population |
| title_full_unstemmed |
Study on the IFNL4 gene ss469415590 variant in Ukrainian population |
| title_sort |
study on the ifnl4 gene ss469415590 variant in ukrainian population |
| publisher |
Інститут молекулярної біології і генетики НАН України |
| publishDate |
2014 |
| topic_facet |
Short Communications |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/154523 |
| citation_txt |
Study on the IFNL4 gene ss469415590 variant in Ukrainian population / A.M. Kucherenko, V.M. Pampukha, L.A. Livshits // Вiopolymers and Cell. — 2014. — Т. 30, № 5. — С. 400-402. — Бібліогр.: 7 назв. — англ. |
| series |
Вiopolymers and Cell |
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| first_indexed |
2025-07-14T06:36:13Z |
| last_indexed |
2025-07-14T06:36:13Z |
| _version_ |
1837603198615945216 |
| fulltext |
SHORT COMMUNICATIONS
UDC 575 + 575.111 + 575.22 + 577.13
Study on the IFNL4 gene ss469415590 variant
in Ukrainian population
A. M. Kucherenko1, 2, V. M. Pampukha1, L. A. Livshits1
1Institute of Molecular Biology and Genetics, NAS 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
kucherenko.a.m@gmail.com
Aim. To determine genotype and allele disribution for the IFNL4 gene ss469415590 and examine it for linkage
with the IL28B gene rs12979860 in Ukrainian population. Methods. The studied group consisted of 100 unrela-
ted donors of Eastern European origin representing the population of Ukraine. Genotyping for the IFNL4 gene
ss469415590 was performed using the amplification-refractory mutation system PCR. Genotyping for the IL28B
gene rs12979860 was performed by the PCR-based restriction fragment length polymorphism assay. Results.
Genotype frequencies for both studied variants showed no significant deviation from those expected according
to Hardy-Weinberg equilibrium. Allelic distribution for ss469415590 was: TT – 0.665, �G – 0.335. Allelic fre-
quencies of rs12979860 were: C – 0.655, T – 0.345. The results of likelihood ratio test indicated a linkage dis-
equilibrium between the studied variants (p > 0.0001), the major alleles ss469415590 TT and rs12979860 C we-
re in phase. The genetic structure of Ukrainian population in terms of two studied polymorphic variants is simi-
lar to the European population presented in the «1000 genomes» project. Conclusions. Considering a tight lin-
kage revealed in Ukrainian population between the ss469415590 variant and rs12979860, a crucial genetic mar-
ker of chronic hepatitis C treatment efficiency, this polymorphism might be a promising target for further investi-
gation as a pharmacogenetic marker.
Key words: ss469415590, rs12979860, IFNL4, linkage disequilibrium.
Introduction. For the past several years wide-range stu-
dies have proven the association of the IL28B gene
rs12979860 with the antiviral therapy efficiency in pa-
tients with chronic hepatitis C (virus genotype 1) as well
as with the spontaneous viral clearance [1, 2]. However,
the exact molecular mechanism for such association re-
mained unclear. According to one of the hypotheses the
rs12979860 was expected to be linked to unknown at
that moment causal variant [2].
The progress in the field has been achieved recently
due to the discovery of previuosly unknown transcript
which expression in hepatocytes was activated by hepa-
titis C virus exposure [3]. It appeared that a new dinuc-
leotide polymorphic variant ss469415590 caused a fra-
me-shift mutation creating an open reading frame – the
IFNL4 (interferon lambda 4) gene [3]. This polymor-
phism was shown to be in a linkage disequillibrium
with rs12979860 in some populations [4] and hence is
being extensively studied now as a genetic marker of
sustained virological response in chronic hepatitis C pa-
tients [1–4].
The aim of the study presented was to determine ge-
notype and allele disribution for ss469415590 and exa-
mine it for the linkage with rs12979860 in Ukrainian
population.
Matherials and methods. The studied group con-
sisted of 100 unrelated donors of Eastern European ori-
gin representing the population of Ukraine. The infor-
med consent was obtained from all participants prior to
enrollment in the study. The study has been approved
by The Bioethical Committee of Institute of Molecular
Biology and Genetics of NAS of Ukraine.
400
ISSN 0233–7657. Biopolymers and Cell. 2014. Vol. 30. N 5. P. 400–402 doi: http://dx.doi.org/10.7124/bc.0008B8
� Institute of Molecular Biology and Genetics, NAS of Ukraine, 2014
The material of the study was genomic DNA extrac-
ted from peripheral blood samples using standard phe-
nol–chloroform technique. Genotyping for the IFNL4
gene ss469415590 was performed using the amplifica-
tion-refractory mutation system (ARMS) PCR. Additio-
nal mismatches were introduced in the primers to avoid
the dimer formation.
The primers sequences were IFNL4�G: TCC TTT
ACA CGG TGA TCG CAG C; IFNL4TT: TCC TTT
ACA CGG TGA TCG CAG AA; and IFNL4com: TGA
TTG ACC CTG AGC CTG CG. The conditions for amp-
lification were as follows: initial denaturation at 95 °C
for 5 min, 30 cycles of 30 s at 95 °C, 30 s at 62°C, and
30 s at 72 °C, followed by 5 min final extension at 72 °C.
The amplification products of 299 bp were visualized
on 2 % agarose gel with ethidium bromide staining. Ge-
notyping for the IL28B gene rs12979860 was perfor-
med by the PCR-based restriction fragment length po-
lymorphism assay as described previously [5].
Statistical analysis has been performed using Gene
Pop statistical package [6]. The �
2 test was used to de-
tect deviations from Hardy-Weinberg equilibrium in ge-
notype distribution.
The likelihood-ratio test has been performed to esti-
mate the linkage disequilibrium between ss469415590 and
rs12979860. P < 0.05 was regarded as a significant value.
Results and discussion. The results of genotyping
for both studied polymorphic variants are presented in
Table 1. Genotype frequencies for both studied variants
showed no significant deviation from those expected ac-
cording to Hardy-Weinberg equilibrium. The �
2 values
for ss469415590 and rs12979860 equaled 0.91 and 0.42
respectively (df = 2). Allelic distribution for ss469415590
was: TT – 0.665, �G – 0.335. Allelic frequencies of
rs12979860 were: C – 0.655, T – 0.345.
The likelihood ratio test was performed to estimate the
genotypic linkage disequilibrium between ss469415590
and rs12979860. The results indicated that the studied
variants are tightly linked (p > 0.0001), the alleles
ss469415590 TT and rs12979860 C were in phase.
The recent data show substantial variation in the
ss469415590 and rs12979860 allele distributions bet-
ween different populations.
Therefore, a comparative analysis of the previously
reported ss469415590 and rs12979860 variant allele
frequencies [7] and the results obtained in this study
was performed (Table 2).
There was no difference between the ss469415590
and rs12979860 allele distribution reported for Europe-
an population and that obtained in this study. Respective
distributions for both polymorphic variants in Eastern
Asian, African, and Ad Mixed American populations
were significantly different from the Ukrainian one.
401
STUDY ON THE IFNL4 GENE ss469415590 VARIANT IN UKRAINIAN POPULATION
rs12979860
ss469415590
D' r2
TT/TT TT/�G �G/�G
CC 40 0 0
1 0.956CT 2 49 0
TT 0 0 9
Table 1
Genotype frequency for studied polymorphic variants
Population
ss469415590
TT
ss469415590
�G
Fisher’s exact test results*
(2-tailed p-value)
European 0.691 0.309 0.4759
Eastern
Asian
0.934 0.066 0.0001
African 0.376 0.624 0.0001
Ad Mixed
American
0.564 0.436 0.0187
Ukrainian 0.665 0.335 –
Population rs12979860 C rs12979860 T
Fisher’s exact test results*
(2-tailed p-value)
European 0.682 0.318 0.4669
Eastern
Asian
0.925 0.075 0.0001
African 0.396 0.604 0.0001
Ad Mixed
American
0.558 0.442 0.0251
Ukrainian 0.655 0.345 –
*Calculated between respective population and Ukrainian populations.
Table 2
Comparative analysis of ss469415590 and rs12979860 allele
Conclusions. In this study we have presented the ge-
notype and allele distribution for the recently discove-
red ss469415590 in the IFNL4 gene in Ukrainian popu-
lation, obtained using ARMS-PCR. The genetic struc-
ture of Ukrainian population in terms of two studied po-
lymorphic variants is similar to the European popula-
tion presented by the «1000 genomes» project.
Taking into account a tight linkage revealed in Uk-
rainian population between the ss469415590 variant
and rs12979860, a crucial genetic marker of chronic he-
patitis C treatment efficiency, this polymorphism might
be a promising target for further investigation as a phar-
macogenetic marker.
Funding. This work was supported by the National
Academy of Sciences of Ukraine (grant number 0112U
002108); and the State of Ukraine (grant number 0113
U006253).
Äîñë³äæåííÿ âàð³àíòà ss469415590 ãåíà IFNL4 â ïîïóëÿö³¿ Óêðà¿íè
À. Ì. Êó÷åðåíêî, Â. Ì. Ïàìïóõà, Ë. À. ˳âøèöü
Ðåçþìå
Ìåòà. Âñòàíîâèòè ðîçïîä³ë ãåíîòèï³â ³ àëåë³â çà âàð³àíòîì
ss469415590 ãåíà IFNL4, à òàêîæ äîñë³äèòè éîãî ç÷åïëåííÿ ç
rs12979860 ó ãåí³ IL28B â ïîïóëÿö³¿ Óêðà¿íè. Ìåòîäè. Äî ãðóïè äî-
ñë³äæåííÿ âõîäèëè 100 íåñïîð³äíåíèõ äîíîð³â ñõ³äíî-ºâðîïåéñü-
êîãî ïîõîäæåííÿ, ÿê³ ïðåäñòàâëÿþòü ïîïóëÿöèþ Óêðà¿íè. Âà-
ð³àíò ss469415590 ãåíà IFNL4 ãåíîòèïóâàëè ìåòîäîì àëåëü-ñïå-
öèô³÷íî¿ ÏËÐ, âàð³àíò rs12979860 ãåíà IL28B – ìåòîäîì ÏËÐ ç
ïîäàëüøèì àíàë³çîì ïîë³ìîðô³çìó äîâæèíè ðåñòðèêö³éíèõ ôðàã-
ìåíò³â. Ðåçóëüòàòè. ×àñòîòè ãåíîòèï³â çà îáîìà äîñë³äæåíè-
ìè âàð³àíòàìè â³äïîâ³äàëè î÷³êóâàíèìè çà ð³âíîâàãîþ Õàðä³-
Âàéíáåðãà. Ðîçïîä³ë ÷àñòîò àëåëåé äëÿ ss469415590 áóëî íàñòóï-
íèì: TT – 0,665, �G – 0,335; äëÿ rs12979860 – C – 0,655, T – 0,345.
Ðåçóëüòàòè òåñòó ñï³ââ³äíîøåííÿ ïðàâäîïîä³áíîñò³ çàñâ³ä÷ó-
þòü íåð³âíîâàãó çà ç÷åïëåííÿì ì³æ äîñë³äæåíèìè ïîë³ìîðô³çìà-
ìè (p > 0.0001), ìàæîðí³ àëåë³ ss469415590 TT òà rs12979860 C
ïåðåáóâàþòü ó ôàç³. Ãåíåòè÷íà ñòðóêòóðà ïîïóëÿö³¿ Óêðà¿íè çà
äâîìà äîñë³äæåíèìè ïîë³ìîðôíèìè âàð³àíòàìè ïîä³áíà äî ºâðî-
ïåéñüêî¿ ïîïóëÿö³¿, îïèñàíî¿ â ïðîåêò³ «1000 ãåíîì³â». Âèñíîâêè.
Áåðó÷è äî óâàãè ò³ñíå ç÷åïëåííÿ ì³æ âàð³àíòîì ss469415590 ³ âà-
æëèâèì ãåíåòè÷íèì ìàðêåðîì åôåêòèâíîñò³ òåðàﳿ õðîí³÷íîãî
ãåïàòèòó Ñ ó ïîïóëÿö³¿ Óêðà¿íè – rs12979860, öåé ïîë³ìîðô³çì
âèäàºòüñÿ ïåðñïåêòèâíèì äëÿ ïîäàëüøîãî äîñë³äæåííÿ éîãî ÿê
ôàðìàêîãåíåòè÷íîãî ìàðêåðà.
Êëþ÷îâ³ ñëîâà: ss469415590, rs12979860, IFNL4, íåð³âíîâàãà
çà ç÷åïëåííÿì.
Èññëåäîâàíèå âàðèàíòà ss469415590 ãåíà IFNL4 â ïîïóëÿöèè
Óêðàèíû
À. Ì. Êó÷åðåíêî, Â. Í. Ïàìïóõà, Ë. À. Ëèâøèö
Ðåçþìå
Öåëü. Óñòàíîâèòü ðàñïðåäåëåíèå ãåíîòèïîâ è àëëåëåé ïî âàðèàí-
òó ss469415590 ãåíà IFNL4, à òàêæå èññëåäîâàòü åãî ñöåïëåíèå ñ
rs12979860 â ãåíå IL28B â ïîïóëÿöèè Óêðàèíû. Ìåòîäû. Â ãðóïïó
èññëåäîâàíèÿ âõîäèëè 100 íåðîäñòâåííûõ äîíîðîâ âîñòî÷íî-åâ-
ðîïåéñêîãî ïðîèñõîæäåíèÿ, ïðåäñòàâëÿþùèå ïîïóëÿöèþ Óêðàè-
íû. Âàðèàíò ss469415590 ãåíà IFNL4 ãåíîòèïèðîâàëè ìåòîäîì
àëëåëü-ñïåöèôè÷åñêîé ÏÖÐ, âàðèàíò rs12979860 ãåíà IL28B – ÏÖÐ
ñ ïîñëåäóþùèì àíàëèçîì ïîëèìîðôèçìà äëèíû ðåñòðèêöèîííûõ
ôðàãìåíòîâ. Ðåçóëüòàòû. ×àñòîòû ãåíîòèïîâ ïî îáîèì èññëå-
äóåìûì âàðèàíòàìè îòâå÷àëè îæèäàåìûìè ïî ðàâíîâåñèþ Õàð-
äè-Âàéíáåðãà. Ðàñïðåäåëåíèå ÷àñòîò àëëåëåé äëÿ ss469415590
áûëî ñëåäóþùèì: TT – 0,665, �G – 0,335, äëÿ rs12979860: C –
0,655, T – 0,345. Ðåçóëüòàòû òåñòà ñîîòíîøåíèÿ ïðàâäîïîäîáèÿ
óêàçûâàþò íà íåðàâíîâåñèå ïî ñöåïëåíèþ ìåæäó èññëåäóåìûìè
ïîëèìîðôèçìàìè (p > 0,0001), ìàæîðíûå àëëåëè ss469415590 TT
è rs12979860 C íàõîäÿòñÿ â ôàçå. Ãåíåòè÷åñêàÿ ñòðóêòóðà ïîïó-
ëÿöèè Óêðàèíû ïî äâóì èññëåäîâàííûì ïîëèìîðôíûì âàðèàíòàì
ïîäîáíà åâðîïåéñêîé ïîïóëÿöèè, îïèñàííîé â ïðîåêòå «1000 ãåíî-
ìîâ». Âûâîäû. Ñ ó÷åòîì òåñíîãî ñöåïëåíèÿ ìåæäó âàðèàíòîì
ss469415590 è âàæíûì ãåíåòè÷åñêèì ìàðêåðîì ýôôåêòèâíîñòè
òåðàïèè õðîíè÷åñêîãî ãåïàòèòà Ñ â ïîïóëÿöèè Óêðàèíû –
rs12979860, ýòîò ïîëèìîðôèçì êàæåòñÿ ïåðñïåêòèâíûì äëÿ
äàëüíåéøåãî èññëåäîâàíèÿ åãî â êà÷åñòâå ôàðìàêîãåíåòè÷åñêîãî
ìàðêåðà.
Êëþ÷åâûå ñëîâà: ss469415590, rs12979860, IFNL4, íåðàâíîâå-
ñèå ïî ñöåïëåíèþ.
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