Study of association between polymorphisms in the PSMB5 (rs11543947) and PSMA3 (rs2348071) genes and multiple sclerosis in Latvians
Functional realization of many signalling proteins and transcription factors implicated in the development and progression of multiple sclerosis is mediated by proteasomes. Aim of this case-control study was to evaluate genetic variations in the PSMB5 and PSMA3 genes encoding proteasomal subunits on...
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nasplib_isofts_kiev_ua-123456789-1544302025-02-09T16:17:29Z Study of association between polymorphisms in the PSMB5 (rs11543947) and PSMA3 (rs2348071) genes and multiple sclerosis in Latvians Оцінка асоціації поліморфізму генів PSMB5 (rs11543947) і PSMA3 (rs2348071) з розсіяним склерозом з-поміж жителів Латвії Оценка ассоциации полиморфизма генов PSMB5 (rs11543947) и PSMA3 (rs2348071) с рассеянным склерозом среди жителей Латвии Kalnina, J. Paramonova, N. Sjakste, N. Sjakste, T. Biomedicine Functional realization of many signalling proteins and transcription factors implicated in the development and progression of multiple sclerosis is mediated by proteasomes. Aim of this case-control study was to evaluate genetic variations in the PSMB5 and PSMA3 genes encoding proteasomal subunits on the susceptibility to multiple sclerosis in Latvians. Methods. The rs11543947 (PSMB5) and rs2348071 (PSMA3) loci were genotyped in 291 multiple sclerosis patients and 305 healthy individuals and analysed general, subtype and sex-specific associations with the disease. Results. Loci rs11543947 and rs2348071 were identified as disease neutral and susceptible respectively. The rs2348071 heterozygous genotype GA showed strong main effect (P < 0.001; OR = 1.891, 95 % CI [1.360–2.628]), and moderate (P < 0.01; OR = 1.663, 95 % CI [1.152– 2.402]) and strong (P < 0.001; OR = 2.459, 95 % CI [1.534–3.943]) association with relapsing-remitting and secondary progressive phases of disease respectively. No genotype-sex interaction associated with multiple sclerosis has been detected. Conclusions. Our results suggest susceptibility of the rs2348071 heterozygous genotype to multiple sclerosis in Latvians. Протеасоми опосередковують виконання функцій багатьох сигнальних білків і факторів транскрипції, залучених до розвитку розсіяного склерозу. Мета. Оцінити можливу асоціацію генетичних варіантів генів PSMB5 і PSMA3 зі схильністю до захворювання на розсіяний склероз з-поміж жителів Латвії. Meтоди. Локуси rs11543947 (PSMB5) і rs2348071 (PSMA3) генотипували у 291 хворого на розсіяний склероз та у 305 здорових індивідів і оцінювали за асоціацією із захворюваністю на розсіяний склероз як такий, із підтипами хвороби і пов’язаною зі статтю асоціацією. Результати. Локус rs11543947виявився не пов’язаним з хворобою, а локус rs2348071 – асоційованим з нею. Гетерозиготний генотип ГА локуса rs2348071 тісно асоційований із захворюванням як таким (P < 0,001; співвідношення шансів (СШ) = 1,891; 95 % ДІ [1.360–2.628]), помірно асоційований (P < 0,01; СШ = 1,663; 95 % ДІ [1,152–2,402]) з ремітуючо-рецидивуючою формою захворювання та сильно (P < 0,001; СШ = 2,459; 95 % ДІ [1,534–3,943]) – зі вторинно прогресуючою формою. Пов’язаної з хворобою взаємодії між статтю і генотипом суб’єкта не відмічено. Висновки. Наші результати вказують на те, що жителі Латвії з гетерозиготним генотипом rs2348071 схильні до захворювання на розсіяний склероз. Протеасомы опосредуют выполнение функций многих сигнальных белков и факторов транскрипции, вовлеченных в развитие рассеянного склероза. Цель. Оценить возможную ассоциацию генетических вариантов генов PSMB5 и PSMA3 с подверженностью заболеванию рассеянным склерозом среди жителей Латвии. Meтоды. Локусы rs11543947 (PSMB5) и rs2348071 (PSMA3) генотипировали у 291 больного рассеянным склерозом и у 305 здоровых индивидов и оценивали по ассоциации с заболеваемостью рассеянным склерозом как таковым, подтипами болезни и связанной с полом ассоциации. Результаты. Локус rs11543947 оказался не связанным с болезнью, а локус rs2348071 – ассоциированным с заболеванием. Гетерозиготный генотип ГА локуса rs2348071 тесно ассоциирован с заболеванием как таковым (P < 0,001; отношение шансов (ОШ) = 1,891, 95 % ДИ [1.360–2.628]), умеренно (P < 0,01; ОШ = 1,663, 95 % ДИ [1,152–2,402]) – с ремиттирующе-рецидивирующей формой заболевания и сильно (P < 0,001; ОШ = 2,459, 95 % ДИ [1,534–3,943]) – со вторично прогрессирущей формой. Связанного с болезнью взаимодействия между полом и генотипом субъекта не отмечено. Выводы. Наши результаты указывают на подверженность жителей Латвии с гетерозиготным генотипом rs2348071 заболеваемости рассеянным склерозом. 2014 Article Study of association between polymorphisms in the PSMB5 (rs11543947) and PSMA3 (rs2348071) genes and multiple sclerosis in Latvians / J. Kalnina, N. Paramonova, N. Sjakste, T. Sjakste // Вiopolymers and Cell. — 2014. — Т. 30, № 4. — С. 305-309. — Бібліогр.: 31 назв. — англ. 0233-7657 DOI: http://dx.doi.org/10.7124/bc.0008A5 https://nasplib.isofts.kiev.ua/handle/123456789/154430 577.21 + 616.832-004.21 en Вiopolymers and Cell application/pdf Інститут молекулярної біології і генетики НАН України |
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Biomedicine Biomedicine Kalnina, J. Paramonova, N. Sjakste, N. Sjakste, T. Study of association between polymorphisms in the PSMB5 (rs11543947) and PSMA3 (rs2348071) genes and multiple sclerosis in Latvians Вiopolymers and Cell |
| description |
Functional realization of many signalling proteins and transcription factors implicated in the development and progression of multiple sclerosis is mediated by proteasomes. Aim of this case-control study was to evaluate genetic variations in the PSMB5 and PSMA3 genes encoding proteasomal subunits on the susceptibility to multiple sclerosis in Latvians. Methods. The rs11543947 (PSMB5) and rs2348071 (PSMA3) loci were genotyped in 291 multiple sclerosis patients and 305 healthy individuals and analysed general, subtype and sex-specific associations with the disease. Results. Loci rs11543947 and rs2348071 were identified as disease neutral and susceptible respectively. The rs2348071 heterozygous genotype GA showed strong main effect (P < 0.001; OR = 1.891, 95 % CI [1.360–2.628]), and moderate (P < 0.01; OR = 1.663, 95 % CI [1.152– 2.402]) and strong (P < 0.001; OR = 2.459, 95 % CI [1.534–3.943]) association with relapsing-remitting and secondary progressive phases of disease respectively. No genotype-sex interaction associated with multiple sclerosis has been detected. Conclusions. Our results suggest susceptibility of the rs2348071 heterozygous genotype to multiple sclerosis in Latvians. |
| format |
Article |
| author |
Kalnina, J. Paramonova, N. Sjakste, N. Sjakste, T. |
| author_facet |
Kalnina, J. Paramonova, N. Sjakste, N. Sjakste, T. |
| author_sort |
Kalnina, J. |
| title |
Study of association between polymorphisms in the PSMB5 (rs11543947) and PSMA3 (rs2348071) genes and multiple sclerosis in Latvians |
| title_short |
Study of association between polymorphisms in the PSMB5 (rs11543947) and PSMA3 (rs2348071) genes and multiple sclerosis in Latvians |
| title_full |
Study of association between polymorphisms in the PSMB5 (rs11543947) and PSMA3 (rs2348071) genes and multiple sclerosis in Latvians |
| title_fullStr |
Study of association between polymorphisms in the PSMB5 (rs11543947) and PSMA3 (rs2348071) genes and multiple sclerosis in Latvians |
| title_full_unstemmed |
Study of association between polymorphisms in the PSMB5 (rs11543947) and PSMA3 (rs2348071) genes and multiple sclerosis in Latvians |
| title_sort |
study of association between polymorphisms in the psmb5 (rs11543947) and psma3 (rs2348071) genes and multiple sclerosis in latvians |
| publisher |
Інститут молекулярної біології і генетики НАН України |
| publishDate |
2014 |
| topic_facet |
Biomedicine |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/154430 |
| citation_txt |
Study of association between polymorphisms in the PSMB5 (rs11543947) and PSMA3 (rs2348071) genes and multiple sclerosis in Latvians / J. Kalnina, N. Paramonova, N. Sjakste, T. Sjakste // Вiopolymers and Cell. — 2014. — Т. 30, № 4. — С. 305-309. — Бібліогр.: 31 назв. — англ. |
| series |
Вiopolymers and Cell |
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| fulltext |
BIOMEDICINE
UDC 577.21 + 616.832-004.21
Study of association between polymorphisms
in the PSMB5 (rs11543947) and PSMA3 (rs2348071)
genes and multiple sclerosis in Latvians
J. Kalnina1, N. Paramonova1, N. Sjakste2, T. Sjakste1
1Genomics and Bioinformatics, Institute of Biology of the University of Latvia,
3, Miera Str., Salaspils, Latvia, LV-2169
2Latvian Institute of Organic Synthesis,
21, Aizkraukles Str., Riga, Latvia, LV-1006
tanja@email.lubi.edu.lv
Functional realization of many signalling proteins and transcription factors implicated in the development and
progression of multiple sclerosis is mediated by proteasomes. Aim of this case-control study was to evaluate ge-
netic variations in the PSMB5 and PSMA3 genes encoding proteasomal subunits on the susceptibility to multiple
sclerosis in Latvians. Methods. The rs11543947 (PSMB5) and rs2348071 (PSMA3) loci were genotyped in 291
multiple sclerosis patients and 305 healthy individuals and analysed general, subtype and sex-specific associa-
tions with the disease. Results. Loci rs11543947 and rs2348071 were identified as disease neutral and sus-
ceptible respectively. The rs2348071 heterozygous genotype GA showed strong main effect (P < 0.001; OR =
= 1.891, 95 % CI [1.360–2.628]), and moderate (P < 0.01; OR = 1.663, 95 % CI [1.152– 2.402]) and strong (P <
< 0.001; OR = 2.459, 95 % CI [1.534–3.943]) association with relapsing-remitting and secondary progressive
phases of disease respectively. No genotype-sex interaction associated with multiple sclerosis has been detected.
Conclusions. Our results suggest susceptibility of the rs2348071 heterozygous genotype to multiple sclerosis in
Latvians.
Keywords: chromosome 14q, proteasomal genes, SNPs, PSMB5, PSMA3, multiple sclerosis.
Introduction. Multiple sclerosis (MS) is the most com-
mon, extremely heterogeneous clinically, chronic in-
flammatory disease of the CNS affecting about 2.5 mil-
lion people around the world (2500 of them in Latvia),
presumably young adults, with onset usually at the se-
cond to fourth decade of life and, similarly to other auto-
immune diseases, women being affected 3–4 times mo-
re frequent than men [1].
About 90 % of MS patients experience the relapsing-
remitting MS course (RRMS), the majority of these pa-
tients enter a secondary progressive course (SPMS)
and about 10 % of MS patients show a primary progres-
sive MS form, characterized by the progression of neuro-
logical disability from onset [2]. The cause of MS is not
clear. The disease develops in genetically susceptible in-
dividuals with contributions of environmental factors,
such as infection, sunlight exposure, vitamin D deficien-
cy [3, 4]. The MS susceptible loci had been identified in
the regions containing genes with immune, co-stimula-
tory, signal transduction functions and related to vita-
min D function [5–10].
Ubiquitin proteasome system (UPS) plays a crucial
role in immunity and its disregulation and/or modulation
may influence the MS development and progression.
The 20S proteasome had been identified as a target of
the humoral autoreactive immune response [11] and a
major autoantigen in MS patients [12]. The proteolytic
activities of proteasomes are reduced in brain tissue of
MS patients [13]. The inhibition of proteasomes and ly-
sosomal proteases involved in major histocompability
complex II antigen presentation was shown to improve
the MS therapeutic effect [11, 14].
305
ISSN 0233–7657. Biopolymers and Cell. 2014. Vol. 30. N 4. P. 305–309 doi: http://dx.doi.org/10.7124/bc.0008A5
� Institute of Molecular Biology and Genetics, NAS of Ukraine, 2014
Modulation of UPS efficiency could be influenced
by polymorphisms in the genes encoding UPS related
proteins. The immunoproteasome PSMB9 codon 60HH
variant was observed to have a reduced risk of develo-
ping MS in HLA-A*02 + Italian females [15].
Coexistence of autoimmune diseases recently evalua-
ted statistically [16] suggests a possibility of their com-
mon origin. In fact, despite generally heterogeneous ge-
netic architecture of the particular disease, some poly-
morphic loci were shown to be shared by MS and other
autoimmune diseases including rheumatoid arthritis [6,
17, 18] and type 1 diabetes mellitus [19, 20].
Genetic variations in the 14q11-24 genes encoding
proteasomal subunits were implicated previously in sus-
ceptibility to autoimmunity, type 2 diabetes mellitus,
cardio-vascular disorders, and population adaptation to
environment [21, 22]. It appears that there is a large po-
tential for some of these mutations also to be associated
with multiple sclerosis.
The aim of the current study was to genotype the
rs11543947 and rs2348071 polymorphisms of the
PSMB5 and PSMA3 genes encoding proteasomal pro-
teins on the MS main, subtype and sex specific associa-
tion in Latvian population.
Materials and methods. Case-control study. The
case group consisted of 281 MS patients referred to the
Latvian Maritime Medicine Center, Vecmilgravis Hos-
pital. MS patients were diagnosed according to the re-
vised 2010 McDonald criteria [23] and assigned to the
RRMS (188 patients) and SPMS (93 patients) groups.
Detailed description of the subject groups is given in
Table 1. Total control group of 305 samples were repre-
sented by the two independent sample sets including the
previously characterized [21, 22] first Latvian popula-
tion study consisting of 191 samples and the second Lat-
vian population study of 114 newly collected samples.
Ethnic origin of the subjects was not recorded; all of them
represent very mixed inhabitants of Riga, forming so-
me «average» genotype for North-East Europe. The da-
ta on the rs11543947 and rs2348071 allele and genoty-
pe frequencies in the first Latvian population sample set
were extracted from [21, 22] to be compared with the
data on genetic diversity obtained for the second Lat-
vian population study and then to be grouped providing
a total control group of 305 healthy individuals. All
controls were carefully assessed to exclude the diagno-
sis of any inflammatory disorders. The studies were ap-
proved by the Central Medical Ethics Commission of
the Republic of Latvia Ministry of Health and informed
consent was obtained from all the studies participants.
DNA extraction and genotyping. Genomic DNA was
extracted from nucleated blood cells using a kit for the
genomic DNA extraction («Fermentas», Lithuania) and
from oral swabs using the salting out method [24]. The
rs11543947 and rs2348071 genotyping technologies
were the same as published previously [21, 22] inclu-
ding primer sequences, basic PCR procedure and ana-
lyses of amplified and digested products. For quality
control, the 16 randomly chosen samples per each mar-
ker were genotyped in duplicate in different experi-
ments. The concordance of genotyping was 100 %. The
genotyping data were verified by direct sequencing of
the corresponding DNA fragments in both directions
306
KALNINA J. ET AL.
Group
Subgroup
Sex Number Age ± SD (years)
Cases
MS
Total 281 42.77 ± 11.10
Females 199 43.21 ± 10.87
Males 82 41.51 ± 11.65
RRMS Total 188 38.80 ± 9.50
Females 132 39.42 ± 9.47
Males 56 37.30 ± 9.50
SPMS Total 93 50.56 ± 9.88
Females 67 50.61 ± 9.53
Males 26 50.42 ± 10.92
Controls
Common
Total 305 38.80 ± 10.54
Females 179 38.78 ± 11.52
Males 126 37.22 ± 9.33
First population Total 191 54.80 ± 18.60
Females 117 56.04 ± 19.84
Males 74 53.56 ± 17.36
Second population Total 114 21.20 ± 2.47
Females 62 21.52 ± 3.19
Males 52 20.88 ± 1.29
Table 1
Description of the sample collections
using the Applied Biosystems 3130xl Genetic Analy-
zer. Loci description and nucleotide numbering are gi-
ven according to the recommended nomenclature sys-
tem (http://www.genomic.unimelb.edu.au/mdi/mutno
men/recs.html). The chromosome 14 GRCh37.p5 assem-
bly (NCBI reference sequence: NC_000014.8) sequen-
ce information was used for loci description.
Data analysis. Single locus genotypes and alleles’
frequencies were estimated by direct gene counting. The
deviation from the Hardy-Weinberg equilibrium (HWE)
and differences between case and control groups in alle-
le, genotype and haplotype frequencies were evaluated
by �
2 using XLSTAT 2013 software for Windows. The
dominant, recessive, over dominant and multiplicative
genetic models for every individual locus were designed
according to [25] and analysed by using 2 � 2 contin-
gency tables. The odds ratio (OR) more than 2 and less
than 0.5 was considered to be clinically significant.
Stratification was performed by MS courses and sex.
Results and discussion. In both MS and the two
Latvian population cohorts, the genotyping call rate
was 100 %. Both markers were found to be in HWE in
controls (c2 = 2.72; p > 0.05). Allele and genotype spect-
rums and distributions were found to be similar (P > 0.05)
for the first (191 samples, [21, 22]) and the second (114
newly collected samples) Latvian population studies for
each marker. The data of both population studies were
grouped and total control group of 305 samples was used
for further analysis. In cases the genotype distribution
corresponded to HWE (c2 = 2.72; P > 0.05) for
rs11543947, however a strong deviation from HWE was
observed for rs2348071 (c2 = 14.14; P < 0.01). Figure il-
lustrates SNPs the genetic diversity in cases and controls.
Depending on the transcript variant, the rs11543947
locus belongs to the PSMB5 gene exon 1 (c. 70 C > T)
or intron 1 (c. 112 + 300 C > T). The allele and genotype
frequencies of this SNP were found to be similar for ca-
ses and controls, RRMS and SPMS cohorts (Figure, A)
as well as for sexes (not shown). Similarly to current da-
ta, in Latvians this SNP did not show any association
with juvenile idiopathic arthritis [22] and bronchial asth-
ma in children (own unpublished data). However, this
locus appears to be susceptible to familial obesity in
Latvian children (own unpublished data).
The rs2348071 SNP is located in the intron 7 of the
PSMA3 gene (c. 543 + 138 G > A or c. 522 + 138 G > A
depending on the transcript variant) and strongly discri-
minates Asians having as major an ancestral allele A
(about 70 %) and other ethnics having as major an
allele G (about 70 %). Transition A � G happened in
Caucasians about 15,000 years ago and was supported
by positive selection in Caucasians over the world [21].
The allele frequencies observed in current study were si-
milar for MS patients and controls, however genotype
distribution was found to be significantly different
(Figure, B). Both common and rare allele homozygotes
appear to be MS protective, however, heterozygous GA
genotype showed strong (p < 0.001) MS main effect,
and strong and moderate association with the SPMS and
RRMS respectively (Table 2).
Previously we have shown [21, 22] that nucleotide
substitution at the rs2348071 may significantly change
patterns of local targets for many regulatory molecules
including proteins of CART, MEF2 and HBPX families
known to mediate transcriptional control of neuronal
differentiation and nucleo- and cytoplasmic ribonucleo-
protein hnRNP A1 implicated in pathogenesis of many
neurodegenerative diseases including multiple sclerosis
[26–28]. Multiple sclerosis patients were shown to ge-
nerate antibodies to hnRNP A1 [26]. This splicing sig-
nal affecting splicing and post-transcriptional modifi-
307
PSMB5 AND PSMA3 POLYMORPHISM IN MULTIPLE SCLEROSIS
A
B
F
re
q
u
en
cy
,
%
F
re
q
u
en
cy
,
%
Minor allele Genotype
0
20
40
60
80
100
T CC CT TT
A GG GA AA
0
20
40
60
1 2 3 4
1 2 3 4
Allele and genotype presentation in MS patients and controls: A –
rs11543947; B – rs2348071; (1 – control; 2 – MS (multiple sclerosis);
3, 4 – RRMS and SPMS (relapsing remitting and secondary progressi-
ve MS course respectively))
cation of majority of expressed genes in mammals, was
shown to interact directly with PSMA3 proteins [29]
and may be potentially involved in regulation of the
PSMA3 gene expression through the rs2348071 allele-
specific targeting. In our previous studies, the rs2348071
heterozygotes were identified also as risk factor in Lat-
vians for juvenile idiopathic arthritis [22], obesity in
children with family history [30] and children bron-
chial asthma (own unpublished observation). In this
study we have tried to analyse separately the groups of
RRMS and SPMS patients, although the latter is con-
sidered to be the result of progression of the former. It
should be mentioned that in some studies [31] the two
forms appear to differ genetically. This provided back-
ground for the design of the study; in fact in our case the
rs2348071 heterozygote genotype was stronger associa-
ted with SPMS than with RRMS (Table 2).
We suggest that the rs2348071 heterozygote geno-
type is a case of heterozygote disadvantage resulted from
the imbalance of the locus functional capacity affecting
human health possibly through the modulation and/or
deregulation of the PSMA3 gene expression, UPS func-
tionality and network of different genes and proteins
involved in pathogenesis of multiple sclerosis and other
neurodegenerative and autoimmune diseases.
Conclusions. Our results suggest susceptibility of the
rs2348071 heterozygous genotype to multiple sclerosis
in Latvians.
Acknowledgements & Funding. Costs of this work
was covered by the European Social Foundation Pro-
ject No 2013/0043/1DP/1.1.1.2.0/13/APIA/VIAA/002.
Îö³íêà àñîö³àö³¿ ïîë³ìîðô³çìó ãåí³â PSMB5 (rs11543947) ³ PSMA3
(rs2348071) ç ðîçñ³ÿíèì ñêëåðîçîì ç-ïîì³æ æèòåë³â Ëàò⳿
². Êàëíèíÿ, Í. Ïàðàìîíîâà, Í. Ñüÿêñòå, T. Ñüÿêñòå
Ðåçþìå
Ïðîòåàñîìè îïîñåðåäêîâóþòü âèêîíàííÿ ôóíêö³é áàãàòüîõ ñèã-
íàëüíèõ á³ëê³â ³ ôàêòîð³â òðàíñêðèïö³¿, çàëó÷åíèõ äî ðîçâèòêó
ðîçñ³ÿíîãî ñêëåðîçó. Ìåòà. Îö³íèòè ìîæëèâó àñîö³àö³þ ãåíåòè÷-
íèõ âàð³àíò³â ãåí³â PSMB5 ³ PSMA3 ç³ ñõèëüí³ñòþ äî çàõâîðþâàí-
íÿ íà ðîçñ³ÿíèé ñêëåðîç ç-ïîì³æ æèòåë³â Ëàò⳿. Meòîäè. Ëîêó-
ñè rs11543947 (PSMB5) ³ rs2348071 (PSMA3) ãåíîòèïóâàëè ó 291
õâîðîãî íà ðîçñ³ÿíèé ñêëåðîç òà ó 305 çäîðîâèõ ³íäèâ³ä³â ³ îö³íþ-
âàëè çà àñîö³àö³ºþ ³ç çàõâîðþâàí³ñòþ íà ðîçñ³ÿíèé ñêëåðîç ÿê òà-
êèé, ³ç ï³äòèïàìè õâîðîáè ³ ïîâ’ÿçàíîþ ç³ ñòàòòþ àñîö³àö³ºþ. Ðå-
çóëüòàòè. Ëîêóñ rs11543947âèÿâèâñÿ íå ïîâ’ÿçàíèì ç õâîðîáîþ,
à ëîêóñ rs2348071 – àñîö³éîâàíèì ç íåþ. Ãåòåðîçèãîòíèé ãåíîòèï
ÃÀ ëîêóñà rs2348071 ò³ñíî àñîö³éîâàíèé ³ç çàõâîðþâàííÿì ÿê òà-
êèì (P < 0,001; ñï³ââ³äíîøåííÿ øàíñ³â (ÑØ) = 1,891; 95 % IJ
[1.360–2.628]), ïîì³ðíî àñîö³éîâàíèé (P < 0,01; ÑØ = 1,663; 95 %
IJ [1,152–2,402]) ç ðåì³òóþ÷î-ðåöèäèâóþ÷îþ ôîðìîþ çàõâîðþ-
âàííÿ òà ñèëüíî (P < 0,001; ÑØ = 2,459; 95 % IJ [1,534–3,943]) –
ç³ âòîðèííî ïðîãðåñóþ÷îþ ôîðìîþ. Ïîâ’ÿçàíî¿ ç õâîðîáîþ âçàº-
ìî䳿 ì³æ ñòàòòþ ³ ãåíîòèïîì ñóá’ºêòà íå â³äì³÷åíî. Âèñíîâêè.
Íàø³ ðåçóëüòàòè âêàçóþòü íà òå, ùî æèòåë³ Ëàò⳿ ç ãåòåðîçè-
ãîòíèì ãåíîòèïîì rs2348071 ñõèëüí³ äî çàõâîðþâàííÿ íà ðîçñ³ÿ-
íèé ñêëåðîç.
Këþ÷îâ³ ñëîâà: õðîìîñîìà 14q, ïðîòåàñîìí³ ãåíè, îäíîíóê-
ëåîòèäíèé ïîë³ìîðô³çì, PSMB5, PSMA3, ðîçñ³ÿíèé ñêëåðîç.
Îöåíêà àññîöèàöèè ïîëèìîðôèçìà ãåíîâ PSMB5 (rs11543947) è
PSMA3 (rs2348071) ñ ðàññåÿííûì ñêëåðîçîì ñðåäè æèòåëåé Ëàòâèè
È. Êàëíûíÿ, Í. Ïàðàìîíîâà, Í. Ñüÿêñòå, T. Ñüÿêñòå
Ðåçþìå
Ïðîòåàñîìû îïîñðåäóþò âûïîëíåíèå ôóíêöèé ìíîãèõ ñèãíàëüíûõ
áåëêîâ è ôàêòîðîâ òðàíñêðèïöèè, âîâëå÷åííûõ â ðàçâèòèå ðàññå-
ÿííîãî ñêëåðîçà. Öåëü. Îöåíèòü âîçìîæíóþ àññîöèàöèþ ãåíåòè-
÷åñêèõ âàðèàíòîâ ãåíîâ PSMB5 è PSMA3 ñ ïîäâåðæåííîñòüþ çà-
áîëåâàíèþ ðàññåÿííûì ñêëåðîçîì ñðåäè æèòåëåé Ëàòâèè. Meòî-
äû. Ëîêóñû rs11543947 (PSMB5) è rs2348071 (PSMA3) ãåíîòèïè-
308
KALNINA J. ET AL.
Genetic model
Control MS RRMS SPMS
P OR [95 % CI]
n = 305 n = 281 n = 188 n = 93
GG vs AA + GA 161 vs 144 119 vs 162 85 vs 103 34 vs 59
PMS < 0.05;
PSPMS < 0.01
ORMS = 0.657
[0.474– 0.910];
ORSPMS = 0.515
[0.320–0.829]
AA vs GG + GA 31 vs 274 14 vs 267 10 vs 178 4 vs 89
PMS < 0.05;
PMS < 0.001
ORMS = 0.463
[0.243–0.883];
ORMS = 1.891
[1.360–2.628]
GA vs GG + AA 113 vs 192 148 vs 133 93 vs 95 55 vs 38
PRRMS < 0.01;
PSPMS < 0.001
ORRRMS = 1.663
[1.152–2.402];
ORSPMS = 2.459
[1.534–3.943]
Table 2
Statistical result on the rs2348071 association with multiple sclerosis
ðîâàëè ó 291 áîëüíîãî ðàññåÿííûì ñêëåðîçîì è ó 305 çäîðîâûõ èí-
äèâèäîâ è îöåíèâàëè ïî àññîöèàöèè ñ çàáîëåâàåìîñòüþ ðàññåÿí-
íûì ñêëåðîçîì êàê òàêîâûì, ïîäòèïàìè áîëåçíè è ñâÿçàííîé ñ ïî-
ëîì àññîöèàöèè. Ðåçóëüòàòû. Ëîêóñ rs11543947 îêàçàëñÿ íå ñâÿ-
çàííûì ñ áîëåçíüþ, à ëîêóñ rs2348071 – àññîöèèðîâàííûì ñ çàáî-
ëåâàíèåì. Ãåòåðîçèãîòíûé ãåíîòèï ÃÀ ëîêóñà rs2348071 òåñíî
àññîöèèðîâàí ñ çàáîëåâàíèåì êàê òàêîâûì (P < 0,001; îòíîøåíèå
øàíñîâ (ÎØ) = 1,891, 95 % ÄÈ [1.360–2.628]), óìåðåííî (P <
0,01; ÎØ = 1,663, 95 % ÄÈ [1,152–2,402]) – ñ ðåìèòòèðóþùå-ðå-
öèäèâèðóþùåé ôîðìîé çàáîëåâàíèÿ è ñèëüíî (P < 0,001; ÎØ =
2,459, 95 % ÄÈ [1,534–3,943]) – ñî âòîðè÷íî ïðîãðåññèðóùåé ôîð-
ìîé. Ñâÿçàííîãî ñ áîëåçíüþ âçàèìîäåéñòâèÿ ìåæäó ïîëîì è ãåíî-
òèïîì ñóáúåêòà íå îòìå÷åíî. Âûâîäû. Íàøè ðåçóëüòàòû óêàçû-
âàþò íà ïîäâåðæåííîñòü æèòåëåé Ëàòâèè ñ ãåòåðîçèãîòíûì
ãåíîòèïîì rs2348071 çàáîëåâàåìîñòè ðàññåÿííûì ñêëåðîçîì.
Këþ÷åâûå ñëîâà: õðîìîñîìà 14q, ïðîòåàñîìíûå ãåíû, îäíî-
íóêëåîòèäíûé ïîëèìîðôèçì, PSMB5, PSMA3, ðàññåÿííûé ñêëåðîç.
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PSMB5 AND PSMA3 POLYMORPHISM IN MULTIPLE SCLEROSIS
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