Association between the PSMB5 and PSMC6 genetic variations and children obesity in the Latvian population
According to the recent data the ubiquitin-proteasome system (UPS) is implicated in the pathogenesis of obesity. Aim of our study was to evaluate a possible association between genetic variations in the PSMB5 and PSMC6 genes and childhood obesity in the Latvian population. Methods. The rs11543947 (...
Saved in:
| Date: | 2014 |
|---|---|
| Main Authors: | , , , , |
| Format: | Article |
| Language: | English |
| Published: |
Інститут молекулярної біології і генетики НАН України
2014
|
| Series: | Вiopolymers and Cell |
| Subjects: | |
| Online Access: | https://nasplib.isofts.kiev.ua/handle/123456789/154586 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Journal Title: | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| Cite this: | Association between the PSMB5 and PSMC6 genetic variations and children obesity in the Latvian population / N. Paramonova, S. Kupca, I. Rumba-Rozenfelde, N. Sjakste, T. Sjakste // Вiopolymers and Cell. — 2014. — Т. 30, № 6. — С. 477-480. — Бібліогр.: 19 назв. — англ. |
Institution
Digital Library of Periodicals of National Academy of Sciences of Ukraine| id |
nasplib_isofts_kiev_ua-123456789-154586 |
|---|---|
| record_format |
dspace |
| spelling |
nasplib_isofts_kiev_ua-123456789-1545862025-02-09T21:01:43Z Association between the PSMB5 and PSMC6 genetic variations and children obesity in the Latvian population Асоціація між генетичними варіантами PSMB5 і PSMC6 та дитячим ожирінням з-поміж жителів Латвії Ассоциация между генетическими вариантами PSMB5 и PSMC6 и детским ожирением среди жителей Латвии Paramonova, N. Kupca, S. Rumba-Rozenfelde, I. Sjakste, N. Sjakste, T. Biomedicine According to the recent data the ubiquitin-proteasome system (UPS) is implicated in the pathogenesis of obesity. Aim of our study was to evaluate a possible association between genetic variations in the PSMB5 and PSMC6 genes and childhood obesity in the Latvian population. Methods. The rs11543947 (PSMB5), rs2295826 and rs2295827 (PSMC6) were genotyped in 94 overweight children versus 191 controls. Stratification was made by family history and sex. Results. Heterozygous genotype at rs11543947 (PSMB5) manifested association with the disease (P < 0.01) in total group and in patients with family history (OR = 2.445 [95 % CI 1.378–4.339] and OR = 2.746 [95 % CI 1.427–5.283], respectively). This genotype was observed more frequently (P < 0.05) in males with family obesity and in females without family history (P < 0.01).The heterozygotes at rs2295826 and rs2295827 showed association (P < 0.01) in obesity (OB), in patients with family history (OR = 2.119 [95 % CI 1.207–3.718] and OR = 2.379 [95 % CI 1.249–4.533], respectively) and in males group. The rs11543947/ rs2295826-rs2295827 multi locus genotype heterozygous at all the studied loci and the haplotype represented by the rare alleles were more frequent in obese children when compared to controls (P < 0.001 and P = 0.0001 respectively). Conclusions. Genetic variations of the PSMB5 (rs11543947) and PSMC6 (rs2295826 and rs2295827) genes can influence childhood obesity in Latvians. Згідно з останніми даними, убіквітин-залежна протеасомна сис- тема бере участь у патогенезі ожиріння. Мета. Оцінити можливий зв’язок між генетичними варіантами протеасомних генів PSMB5 і PSMC6 та схильністю до захворювання дитячим ожирінням у Латвійській популяции. Методи. Локуси rs11543947 (PSMB5), rs2295826 і rs2295827 (PSMC6) генотипували у 94 дітей з надлишковою вагою і у 191 здорового індивіда. Оцінку проводили за асоціацією з ожирінням як таким, за сімейною історією та за статтю. Результати. Гетерозиготний генотип, який належить до локусу rs11543947 (PSMB5), виявився помірно асоційованим ( Р < 0,01) із захворюванням як таким і з ожирінням з сімейною історією (співвідношення шансів СШ = 2,445 [95 % ДІ 1.378–4.339] і СШ = 2,746 [95 % ДІ 1.427–5.283] відповідно). Цей генотип найчастіше спостерігався у чоловіків із сімейною історією ожиріння (P < 0,05) та у жінок без сімейної історії (P < 0,01). Гетерозиготні генотипи по локусах rs2295826 і rs2295827 знайдено в помірній асоціації (P < 0,01) в основній групі захворювання і у пацієнтів з сімейною історією (СШ = 2,119 [95 % ДІ 1.207–3.718] і СШ = 2,379 [95 % ДІ 1.249–4.533] відповідно), а також у чоловіків. Багатолокусний генотип rs11543947/rs2295826-rs2295827, представлений гетерозиготами по всіх локусах, і гаплотип, представлений рідкісними алелями, були найчастішими у групі хворих на ожиріння порівняно з контрольною групою (Р < 0,001 і Р = 0,0001 відповідно). Висновки. Генетичні варіації локусів PSMB5 (rs11543947) і PSMC6 (rs2295826 і rs2295827) можуть впливати на схильність до захворювання ожирінням у детей Латвійської популяції. Согласно последним данным, убиквитин-зависимая протеасомная система участвует в патогенезе ожирения. Цель. Оценить возможную связь между генетическими вариантами протеасомных генов PSMB5 и PSMC6 и подверженностью заболеванию детским ожирением в Латвийской популяции. Методы. Локусы rs11543947 (PSMB5), rs2295826 и rs2295827 (PSMC6) генотипировали у 94 детей с избыточным весом и у 191 здорового индивида. Оценку проводили по ассоциации с ожирением как таковым, с семейной историей и с полом. Результаты. Гетерозиготный генотип, относящийся к локусу rs11543947 (PSMB5), оказался умеренно ассоциированным ( Р < 0,01) с заболеванием как таковым и с ожирением с семейной историей (отношение шансов ОШ = 2,445 [95 % ДИ 1.378–4.339] и ОШ = 2,746 [95 % ДИ 1.427– 5.283] соответственно). Этот генотип наиболее часто наблюдался у мужчин с семейной историей ожирения (p < 0,05) и у женщин без семейной истории (P < 0,01). Гетерозиготные генотипы по локусам rs2295826 и rs2295827 найдены в умеренной ассоциации (P < 0,01) в основной группе заболевания и у пациентов с семейной историей (ОШ = 2,119 [95 % ДИ 1.207–3.718] и ОШ = 2,379 [95 % ДИ 1.249–4.533] соответственно) и у мужчин. Многолокусный генотип rs11543947/rs2295826-rs2295827, представленный гетерозиготами по всем локусам, и гаплотип, представленный редкими аллелями, были наиболее частыми в группе больных ожирением по сравнению с контрольной группой (Р < 0,001 и Р = 0,0001 соответственно). Выводы. Генетические вариации локусов PSMB5 (rs11543947) и PSMC6 (rs2295826 и rs2295827) могут влиять на подверженность заболеваемости ожирением у детей в Латвийской популяции. 2014 Article Association between the PSMB5 and PSMC6 genetic variations and children obesity in the Latvian population / N. Paramonova, S. Kupca, I. Rumba-Rozenfelde, N. Sjakste, T. Sjakste // Вiopolymers and Cell. — 2014. — Т. 30, № 6. — С. 477-480. — Бібліогр.: 19 назв. — англ. 0233-7657 DOI: http://dx.doi.org/10.7124/bc.0008C3 https://nasplib.isofts.kiev.ua/handle/123456789/154586 577.21 + 616.248 en Вiopolymers and Cell application/pdf Інститут молекулярної біології і генетики НАН України |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| collection |
DSpace DC |
| language |
English |
| topic |
Biomedicine Biomedicine |
| spellingShingle |
Biomedicine Biomedicine Paramonova, N. Kupca, S. Rumba-Rozenfelde, I. Sjakste, N. Sjakste, T. Association between the PSMB5 and PSMC6 genetic variations and children obesity in the Latvian population Вiopolymers and Cell |
| description |
According to the recent data the ubiquitin-proteasome system (UPS) is implicated in the pathogenesis of obesity. Aim of our study was to evaluate a possible association between genetic variations in the PSMB5 and PSMC6 genes and childhood obesity in the Latvian population. Methods. The rs11543947 (PSMB5), rs2295826 and rs2295827 (PSMC6) were genotyped in 94 overweight children versus 191 controls. Stratification was made by family history and sex. Results. Heterozygous genotype at rs11543947 (PSMB5) manifested association with the disease (P < 0.01) in total group and in patients with family history (OR = 2.445 [95 % CI 1.378–4.339] and OR = 2.746 [95 % CI 1.427–5.283], respectively). This genotype was observed more frequently (P < 0.05) in males with family obesity and in females without family history (P < 0.01).The heterozygotes at rs2295826 and rs2295827 showed association (P < 0.01) in obesity (OB), in patients with family history (OR = 2.119 [95 % CI 1.207–3.718] and OR = 2.379 [95 % CI 1.249–4.533], respectively) and in males group. The rs11543947/ rs2295826-rs2295827 multi locus genotype heterozygous at all the studied loci and the haplotype represented by the rare alleles were more frequent in obese children when compared to controls (P < 0.001 and P = 0.0001 respectively). Conclusions. Genetic variations of the PSMB5 (rs11543947) and PSMC6 (rs2295826 and rs2295827) genes can influence childhood obesity in Latvians. |
| format |
Article |
| author |
Paramonova, N. Kupca, S. Rumba-Rozenfelde, I. Sjakste, N. Sjakste, T. |
| author_facet |
Paramonova, N. Kupca, S. Rumba-Rozenfelde, I. Sjakste, N. Sjakste, T. |
| author_sort |
Paramonova, N. |
| title |
Association between the PSMB5 and PSMC6 genetic variations and children obesity in the Latvian population |
| title_short |
Association between the PSMB5 and PSMC6 genetic variations and children obesity in the Latvian population |
| title_full |
Association between the PSMB5 and PSMC6 genetic variations and children obesity in the Latvian population |
| title_fullStr |
Association between the PSMB5 and PSMC6 genetic variations and children obesity in the Latvian population |
| title_full_unstemmed |
Association between the PSMB5 and PSMC6 genetic variations and children obesity in the Latvian population |
| title_sort |
association between the psmb5 and psmc6 genetic variations and children obesity in the latvian population |
| publisher |
Інститут молекулярної біології і генетики НАН України |
| publishDate |
2014 |
| topic_facet |
Biomedicine |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/154586 |
| citation_txt |
Association between the PSMB5 and PSMC6 genetic variations and children obesity in the Latvian population / N. Paramonova, S. Kupca, I. Rumba-Rozenfelde, N. Sjakste, T. Sjakste // Вiopolymers and Cell. — 2014. — Т. 30, № 6. — С. 477-480. — Бібліогр.: 19 назв. — англ. |
| series |
Вiopolymers and Cell |
| work_keys_str_mv |
AT paramonovan associationbetweenthepsmb5andpsmc6geneticvariationsandchildrenobesityinthelatvianpopulation AT kupcas associationbetweenthepsmb5andpsmc6geneticvariationsandchildrenobesityinthelatvianpopulation AT rumbarozenfeldei associationbetweenthepsmb5andpsmc6geneticvariationsandchildrenobesityinthelatvianpopulation AT sjaksten associationbetweenthepsmb5andpsmc6geneticvariationsandchildrenobesityinthelatvianpopulation AT sjakstet associationbetweenthepsmb5andpsmc6geneticvariationsandchildrenobesityinthelatvianpopulation AT paramonovan asocíacíâmížgenetičnimivaríantamipsmb5ípsmc6taditâčimožirínnâmzpomížžitelívlatvíí AT kupcas asocíacíâmížgenetičnimivaríantamipsmb5ípsmc6taditâčimožirínnâmzpomížžitelívlatvíí AT rumbarozenfeldei asocíacíâmížgenetičnimivaríantamipsmb5ípsmc6taditâčimožirínnâmzpomížžitelívlatvíí AT sjaksten asocíacíâmížgenetičnimivaríantamipsmb5ípsmc6taditâčimožirínnâmzpomížžitelívlatvíí AT sjakstet asocíacíâmížgenetičnimivaríantamipsmb5ípsmc6taditâčimožirínnâmzpomížžitelívlatvíí AT paramonovan associaciâmeždugenetičeskimivariantamipsmb5ipsmc6idetskimožireniemsredižiteleilatvii AT kupcas associaciâmeždugenetičeskimivariantamipsmb5ipsmc6idetskimožireniemsredižiteleilatvii AT rumbarozenfeldei associaciâmeždugenetičeskimivariantamipsmb5ipsmc6idetskimožireniemsredižiteleilatvii AT sjaksten associaciâmeždugenetičeskimivariantamipsmb5ipsmc6idetskimožireniemsredižiteleilatvii AT sjakstet associaciâmeždugenetičeskimivariantamipsmb5ipsmc6idetskimožireniemsredižiteleilatvii |
| first_indexed |
2025-11-30T17:45:24Z |
| last_indexed |
2025-11-30T17:45:24Z |
| _version_ |
1850238282916429824 |
| fulltext |
BIOMEDICINE
UDC 577.21 + 616.248
Association between the PSMB5 and PSMC6 genetic
variations and children obesity in the Latvian population
N. Paramonova1, S. Kupca2, 3, I. Rumba-Rozenfelde2, 3, N. Sjakste2, 4, T. Sjakste1
1Genomics and Bioinformatics, Institute of Biology of the University of Latvia
3, Miera Str., Salaspils, Latvia, LV2169
2Faculty of Medicine, University of Latvia
19, Raina Bulv., Riga, Latvia, LV1586
3University Children Hospital
20, Juglas Str., Riga, Latvia, LV-1079
4Latvian Institute of Organic Synthesis
21, Aizkraukles Str., Riga, Latvia, LV1006
natasa@email.lubi.edu.lv
According to the recent data the ubiquitin-proteasome system (UPS) is implicated in the pathogenesis of obesity.
Aim of our study was to evaluate a possible association between genetic variations in the PSMB5 and PSMC6
genes and childhood obesity in the Latvian population. Methods. The rs11543947 (PSMB5), rs2295826 and
rs2295827 (PSMC6) were genotyped in 94 overweight children versus 191 controls. Stratification was made by
family history and sex. Results. Heterozygous genotype at rs11543947 (PSMB5) manifested association with the
disease (P < 0.01) in total group and in patients with family history (OR = 2.445 [95 % CI 1.378–4.339] and OR =
= 2.746 [95 % CI 1.427–5.283], respectively). This genotype was observed more frequently (P < 0.05) in males
with family obesity and in females without family history (P < 0.01).The heterozygotes at rs2295826 and
rs2295827 showed association (P < 0.01) in obesity (OB), in patients with family history (OR = 2.119 [95 % CI
1.207–3.718] and OR = 2.379 [95 % CI 1.249–4.533], respectively) and in males group. The rs11543947/
rs2295826-rs2295827 multi locus genotype heterozygous at all the studied loci and the haplotype represented by
the rare alleles were more frequent in obese children when compared to controls (P < 0.001 and P = 0.0001 res-
pectively). Conclusions. Genetic variations of the PSMB5 (rs11543947) and PSMC6 (rs2295826 and rs2295827)
genes can influence childhood obesity in Latvians.
Keywords: PSMB5, PSMC6, SNPs, obesity, familial obesity, genotype–sex interaction.
Introduction. The ubiquitin-proteasome system (UPS)
has been recently shown to be implicated in the patho-
genesis of obesity (OB). It has been demonstrated that
plasma ubiquitin and proteasome levels inversely corre-
lated with a male body mass index in Southern Taiwan
and Japanese population [1, 2] and that the proteasome
dysfunction mediated the obesity-induced endoplas-
mic reticulum stress and insulin resistance in the liver
[3]. A significant association was found between gene-
tic variants of the PSMD9 gene and obesity-associated
phenotypes in Italians [4]. The mutation in the PSMB8
gene has been reported to be associated with the autoin-
flammatory syndrome with lipodystrophy in Japanese
[5]. Earlier we have detected the association of the
PSMA3 gene polymorphisms with susceptibility to obe-
sity in Latvian children [6].
The current study was aimed to elucidate whether
the single nucleotide polymorphisms (SNPs) of the
PSMB5 (rs11543947) and PSMC6 (rs2295826 and
rs2295827) genes are associated with the children obe-
sity in the Latvian population.
Materials and methods. Case/control groups (94
obese children and 191 controls, respectively) were des-
cribed previously [6, 7]. The rs2295826 and rs2295827
477
ISSN 0233–7657. Biopolymers and Cell. 2014. Vol. 30. N 6. P. 477–480 doi: http://dx.doi.org/10.7124/bc.0008C3
� Institute of Molecular Biology and Genetics, NAS of Ukraine, 2014
genotyping data for controls were extracted from
Sjakste et al. [7] and used in current study for the as-
sociation analysis. The study was approved by the Cent-
ral Medical Ethics Commission of the Latvian Ministry
of Health.
The PSMB5 (rs11543947) and PSMC6 (rs2295826,
rs2295827) genotyping procedures and analysis of amp-
lified and digested products were the same as published
previously [7, 8].
Single loci (SLGs) and multi locus rs11543947/
rs2295826-rs2295827 genotypes and alleles’ frequen-
cies were estimated by direct gene counting. The devia-
tions from the Hardy-Weinberg equilibrium and asso-
ciation/correlation analyses were tested by the �
2 test
(allele, multi-loci genotype frequencies, recessive and
dominant, over dominant and multiplicative models)
using PAST (version 3.03) software for Windows [9].
Only 2 < OR < 0.5 was considered to be clinically signi-
ficant. DnaSP version 5 (http://www.ub.es/dnasp, [10])
was used to reconstruct the haplotypes from un-phased
genotypes, and to evaluate the nucleotide and haploty-
pe genetic diversity and pairwise linkage disequilib-
rium (LD) between the loci (D' and r2). Stratification
was performed by the sex and obesity family history.
Results and discussion. In both cases and controls
genotyping call rate was 100 %. Homozygotes on com-
mon alleles for all loci were observed more frequently
in controls than obese patients (more than 80 % and less
than 70 %, respectively) and the tendencies were similar
in children with and without family history (Table). The
dominant and multiplicative models [11] were the most
informative to reveal OB susceptible genotypes and alle-
les, respectively.
The rs11543947 heterozygous genotype showed a
modest (P < 0.01) association with OB risk in total group
and in children with familial OB. A rare T allele was ob-
served more frequently (P < 0.05) in both these groups
than in controls. The rs2295826 and rs2295827 loci al-
leles in OB patients were found to be in full linkage (D' =
= 1; r2 = 1), as it was previously reported for Latvian
controls [7]. These loci heterozygous genotypes were
found to be in association (P < 0.01) with OB and fami-
lial OB groups. Rare alleles manifested nominal asso-
ciation with the disease (P < 0.05).
The family background was found to be an obesity
risk factor (OR = 1.86 for mother; OR = 2.98 for sib-
lings) among Chinese male youths [12]. A significant
difference (p < 0.01) was observed between the sub-
jects having the obesity family history and non-obese
controls in rs2348071 heterozygous genotype frequen-
cies at the PSMA3 locus [6]. Bennet et al. have shown
[13] that a greater predisposition to diabetes in Middle
Eastern immigrants may be explained by a more exten-
sive family history of the disorder.
In the current association study an interaction bet-
ween sexes and familial obesity was revealed. The
rs11543947 risk CT genotype and rare T allele were
found more frequently in males with family obesity (P <
0.05) and in females without family history (P < 0.01).
The rs2295826 and rs2295827 heterozygous genotypes
and minor alleles were associated (P < 0.01 and P <
0.05, respectively) with all OB subgroups in males.
Sex specific differences in incidence and severity
are also well known features for epidemiology of obe-
sity. The sex-influenced association of obesity with ge-
netic variations at the LYPLAL1 locus, which encodes a
lipase/esterase expressed in adipose tissue was sug-
gested [14]. Seven new loci exhibited marked sexual di-
morphism with a stronger effect on weight-hip ratio in
women than men (P for sex difference < 0.05 to P <
0.0001) [15].
Thus, our data on the importance of interactions bet-
ween the family history and sex for susceptibility for
childhood obesity confirm the previous reports. Ob-
viously having in our disposition a collection of a relati-
vely small number of samples we can't reach high statis-
tical reliability of results. The small number of subjects
and the wide range of values (reflected by large stan-
dard deviation) precluded reliable statistical confirma-
tion of this admission. However, even a study with small
subject number reveals the trend on the association of
the disease and can predict the common trends of as-
sociation also for larger sample groups collected in lar-
ger populations.
The rs11543947/rs2295826-rs2295827 three locus
genotype heterozygous at all the loci involved was found
about four times more frequently in OB patients than in
controls (about 3 and 13 %, respectively) and showed to
be OB susceptible (P < 0.001). The multi locus T/G-T
haplotype represented by rare alleles of the studied loci
was more frequent (P = 0.0001) in obese children when
compared to controls (0.5 and 6 %, respectively).
478
PARAMONOVA N. ET AL.
Susceptibility of genes encoding proteasome subu-
nits to the immunity related disorders was studied pre-
viously in Latvians. The rs1048990 (PSMA6), rs2295826
and rs2295827 (PSMC6), rs2348071 (PSMA3) were
found to be associated with susceptibility to bronchial
asthma [16]. The rs2277460 (PSMA6), rs2295826 and
rs2295827 (PSMC6) and rs2348071 (PSMA3) manifes-
ted association with juvenile idiopathic arthritis [8].
The rs2348071 (PSMA3) was found to be associated with
multiple sclerosis [17] and childhood obesity [6].
Obesity in the young characterized by visceral fat
accumulation has been shown to be a major risk factor
for adult-onset type 2 diabetes mellitus [18, 19], there-
fore, we cannot exclude in our cases a possibility of the
development of diabetes in adult age.
Conclusions. The genetic variation of PSMB5
(rs11543947) and PSMC6 (rs2295826 and rs2295827)
14q proteasomes subunits can influence OB in Latvians.
Acknowledgements & Funding. This study was
supported by the Latvian National Research Program
«Biomedicine 2014».
Àñîö³àö³ÿ ì³æ ãåíåòè÷íèìè âàð³àíòàìè PSMB5 ³ PSMC6
òà äèòÿ÷èì îæèð³ííÿì ç-ïîì³æ æèòåë³â Ëàò⳿
Í. Ïàðàìîíîâà, Ñ. Êóï÷à, È. Ðóìáà-Ðîçåíôåëäå,
Í. Ñüÿêñòå, Ò. Ñüÿêñòå
Ðåçþìå
Çã³äíî ç îñòàíí³ìè äàíèìè, óá³êâ³òèí-çàëåæíà ïðîòåàñîìíà ñèñ-
òåìà áåðå ó÷àñòü ó ïàòîãåíåç³ îæèð³ííÿ. Ìåòà. Îö³íèòè ìîæëè-
âèé çâ’ÿçîê ì³æ ãåíåòè÷íèìè âàð³àíòàìè ïðîòåàñîìíèõ ãåí³â
PSMB5 ³ PSMC6 òà ñõèëüí³ñòþ äî çàõâîðþâàííÿ äèòÿ÷èì îæèð³í-
479
CHILDHOOD OBESITY ASSOCIATED WITH PSMB5 AND PSMC6 POLYMORPHISMS
Gene/SNP ID MA/Genotype
Number (frequency %) Statistically significant association
Control, n =191 OB, n = 94 FH, n = 59 NFH, n = 32 P OR [95 % CI]
PSMB5/rs11543947 T 34 (8.90) 31 (16.49) 21 (17.80) 10 (15.63) < 0.05
OB
2.021 [1.247–3.391]
– – – – < 0.05
FH
2.216 [1.236–3.971]
– – – – > 0.05
NFH
– –
CC 159 (83.25) 63 (67.02) 38 (64.41) 22 (68.75) – – –
CT 30 (15.71) 31 (32.98) 21 (35.59) 10 (31.25) < 0.01
OB
2.445 [1.378–4.339]
– – – – < 0.01
FH
2.746 [1.427–5.283]
TT 2 (1.04) No No No – – –
PSMC6/rs2295826-
rs2295827 (D' = 1;
r
2
= 1)*
G 40 (10.47) 33 (17.55) 22 (18.64) 10 (15.63) < 0.05
OB
1.820 [1.109–2.987]
– – – – < 0.05
FH
1.959 [1.116–3.439]
– – – – > 0.05
NFH
– –
AA 155 (81.15) 63 (67.02) 38 (64.41) 23 (71.88) – – –
AG 32 (16.75) 29 (30.85) 20 (33.90) 8 (25.00) < 0.01
OB
2.119 [1.207–3.718]
– – – – < 0.01
FH
2.379 [1.249–4.533]
– – – – > 0.05
NFH
– –
GG 4 (2.10) 2 (2.13) 1 (1.69) 1 (3.13) – – –
Loci L1/L2-L3 – – – – – – –
Heterozygous
genotypes
CT/AG-CT 5 (2.62) 12 (12.77) 7 (11.86) 5 (15.63) < 0.001
OB
9.018 [2.967–27.410]
Rare alleles haplotype T/G-T 2 (0.52) 11 (5.85) 7 (5.93) 4 (6.25) 0.0001
OB
13.660 [2.895–62.524]
N o t e. OB patients were represented by 59 children with obesity family history, 32 children without family history and there were no data on
familial history of obesity in 3 cases. Abbreviations: OB – Obesity; FH – obesity with family history; NFH – obesity without family history.
*Alleles and genotypes frequencies of the rs2295826 and rs2295827 were found in full linkage. L1/L2-L3 corresponds to the rs11543947 and
rs2295826-rs2295827 loci respectively.
SNPs association with childhood obesity in common cohort, with and without family history groups
íÿì ó Ëàòâ³éñüê³é ïîïóëÿöèè. Ìåòîäè. Ëîêóñè rs11543947 (PSMB5),
rs2295826 ³ rs2295827 (PSMC6) ãåíîòèïóâàëè ó 94 ä³òåé ç íàäëèø-
êîâîþ âàãîþ ³ ó 191 çäîðîâîãî ³íäèâ³äà. Îö³íêó ïðîâîäèëè çà àñîö³-
àö³ºþ ç îæèð³ííÿì ÿê òàêèì, çà ñ³ìåéíîþ ³ñòîð³ºþ òà çà ñòàò-
òþ. Ðåçóëüòàòè. Ãåòåðîçèãîòíèé ãåíîòèï, ÿêèé íàëåæèòü äî
ëîêóñó rs11543947 (PSMB5), âèÿâèâñÿ ïîì³ðíî àñîö³éîâàíèì ( Ð <
0,01) ³ç çàõâîðþâàííÿì ÿê òàêèì ³ ç îæèð³ííÿì ç ñ³ìåéíîþ ³ñòî-
ð³ºþ (ñï³ââ³äíîøåííÿ øàíñ³â ÑØ = 2,445 [95 % IJ 1.378–4.339] ³
ÑØ = 2,746 [95 % IJ 1.427–5.283] â³äïîâ³äíî). Öåé ãåíîòèï íàé-
÷àñò³øå ñïîñòåð³ãàâñÿ ó ÷îëîâ³ê³â ³ç ñ³ìåéíîþ ³ñòîð³ºþ îæèð³ííÿ
(P < 0,05) òà ó æ³íîê áåç ñ³ìåéíî¿ ³ñòî𳿠(P < 0,01). Ãåòåðîçèãîò-
í³ ãåíîòèïè ïî ëîêóñàõ rs2295826 ³ rs2295827 çíàéäåíî â ïîì³ðí³é
àñîö³àö³¿ (P < 0,01) â îñíîâí³é ãðóï³ çàõâîðþâàííÿ ³ ó ïàö³ºíò³â ç
ñ³ìåéíîþ ³ñòîð³ºþ (ÑØ = 2,119 [95 % IJ 1.207–3.718] ³ ÑØ =
= 2,379 [95 % IJ 1.249–4.533] â³äïîâ³äíî), à òàêîæ ó ÷îëîâ³ê³â.
Áàãàòîëîêóñíèé ãåíîòèï rs11543947/rs2295826-rs2295827, ïðåä-
ñòàâëåíèé ãåòåðîçèãîòàìè ïî âñ³õ ëîêóñàõ, ³ ãàïëîòèï, ïðåäñòàâëå-
íèé ð³äê³ñíèìè àëåëÿìè, áóëè íàé÷àñò³øèìè ó ãðóï³ õâîðèõ íà îæè-
ð³ííÿ ïîð³âíÿíî ç êîíòðîëüíîþ ãðóïîþ (Ð < 0,001 ³ Ð = 0,0001 â³äïî-
â³äíî). Âèñíîâêè. Ãåíåòè÷í³ âàð³àö³¿ ëîêóñ³â PSMB5 (rs11543947)
³ PSMC6 (rs2295826 ³ rs2295827) ìîæóòü âïëèâàòè íà ñõèëüí³ñòü
äî çàõâîðþâàííÿ îæèð³ííÿì ó äåòåé Ëàòâ³éñüêî¿ ïîïóëÿö³¿.
Êëþ÷îâ³ ñëîâà: PSMB5, PSMC6, SNPs, îæèð³ííÿ, ñ³ìåéíå îæè-
ð³ííÿ, âçàºìîä³ÿ ãåíîòèï–ñòàòü.
Àññîöèàöèÿ ìåæäó ãåíåòè÷åñêèìè âàðèàíòàìè PSMB5 è PSMC6 è
äåòñêèì îæèðåíèåì ñðåäè æèòåëåé Ëàòâèè
Í. Ïàðàìîíîâà, Ñ. Êóï÷à, È. Ðóìáà-Ðîçåíôåëäå,
Í. Ñüÿêñòå, Ò. Ñüÿêñòå
Ðåçþìå
Ñîãëàñíî ïîñëåäíèì äàííûì, óáèêâèòèí-çàâèñèìàÿ ïðîòåàñîì-
íàÿ ñèñòåìà ó÷àñòâóåò â ïàòîãåíåçå îæèðåíèÿ. Öåëü. Îöåíèòü
âîçìîæíóþ ñâÿçü ìåæäó ãåíåòè÷åñêèìè âàðèàíòàìè ïðîòåàñîì-
íûõ ãåíîâ PSMB5 è PSMC6 è ïîäâåðæåííîñòüþ çàáîëåâàíèþ äåò-
ñêèì îæèðåíèåì â Ëàòâèéñêîé ïîïóëÿöèè. Ìåòîäû. Ëîêóñû
rs11543947 (PSMB5), rs2295826 è rs2295827 (PSMC6) ãåíîòèïè-
ðîâàëè ó 94 äåòåé ñ èçáûòî÷íûì âåñîì è ó 191 çäîðîâîãî èíäèâè-
äà. Îöåíêó ïðîâîäèëè ïî àññîöèàöèè ñ îæèðåíèåì êàê òàêîâûì, ñ
ñåìåéíîé èñòîðèåé è ñ ïîëîì. Ðåçóëüòàòû. Ãåòåðîçèãîòíûé ãå-
íîòèï, îòíîñÿùèéñÿ ê ëîêóñó rs11543947 (PSMB5), îêàçàëñÿ óìå-
ðåííî àññîöèèðîâàííûì ( Ð < 0,01) ñ çàáîëåâàíèåì êàê òàêîâûì è
ñ îæèðåíèåì ñ ñåìåéíîé èñòîðèåé (îòíîøåíèå øàíñîâ ÎØ =
= 2,445 [95 % ÄÈ 1.378–4.339] è ÎØ = 2,746 [95 % ÄÈ 1.427–
5.283] ñîîòâåòñòâåííî). Ýòîò ãåíîòèï íàèáîëåå ÷àñòî íàáëþ-
äàëñÿ ó ìóæ÷èí ñ ñåìåéíîé èñòîðèåé îæèðåíèÿ (p < 0,05) è ó æåí-
ùèí áåç ñåìåéíîé èñòîðèè (P < 0,01). Ãåòåðîçèãîòíûå ãåíîòèïû
ïî ëîêóñàì rs2295826 è rs2295827 íàéäåíû â óìåðåííîé àññîöèà-
öèè (P < 0,01) â îñíîâíîé ãðóïïå çàáîëåâàíèÿ è ó ïàöèåíòîâ ñ ñå-
ìåéíîé èñòîðèåé (ÎØ = 2,119 [95 % ÄÈ 1.207–3.718] è ÎØ =
= 2,379 [95 % ÄÈ 1.249–4.533] ñîîòâåòñòâåííî) è ó ìóæ÷èí. Ìíî-
ãîëîêóñíûé ãåíîòèï rs11543947/rs2295826-rs2295827, ïðåäñòàâ-
ëåííûé ãåòåðîçèãîòàìè ïî âñåì ëîêóñàì, è ãàïëîòèï, ïðåäñòàâ-
ëåííûé ðåäêèìè àëëåëÿìè, áûëè íàèáîëåå ÷àñòûìè â ãðóïïå áîëü-
íûõ îæèðåíèåì ïî ñðàâíåíèþ ñ êîíòðîëüíîé ãðóïïîé (Ð < 0,001 è
Ð = 0,0001 ñîîòâåòñòâåííî). Âûâîäû. Ãåíåòè÷åñêèå âàðèàöèè ëî-
êóñîâ PSMB5 (rs11543947) è PSMC6 (rs2295826 è rs2295827) ìî-
ãóò âëèÿòü íà ïîäâåðæåííîñòü çàáîëåâàåìîñòè îæèðåíèåì ó äå-
òåé â Ëàòâèéñêîé ïîïóëÿöèè.
Êëþ÷åâûå ñëîâà: PSMB5, PSMC6, SNPs, îæèðåíèå, ñåìåéíîå
îæèðåíèå, âçàèìîäåéñòâèå ãåíîòèï–ïîë.
REFERENCES
1. Chang TL, Chang CJ, Lee WY, Lin MN, Huang YW, Fan K. The
roles of ubiquitin and 26S proteasome in human obesity. Metabo-
lism. 2009;58(11):1643–8.
2. Sakamoto K, Sato Y, Sei M, Ewis AA, Nakahori Y. Proteasome ac-
tivity correlates with male BMI and contributes to the differentia-
tion of adipocyte in hADSC. Endocrine. 2010;37(2):274–9.
3. Otoda T, Takamura T, Misu H, et al. Proteasome dysfunction me-
diates obesity-induced endoplasmic reticulum stress and insulin
resistance in the liver. Diabetes. 2013;62(3):811–24.
4. Gragnoli C. Overweight condition and waist circumference and a
candidate gene within the 12q24 locus. Cardiovasc Diabetol.
2013;12:2.
5. Kitamura A, Maekawa Y, Uehara H, et al. A mutation in the im-
munoproteasome subunit PSMB8 causes autoinflammation and li-
podystrophy in humans. J Clin Invest. 2011;121(10):4150–60.
6. Kupca S, Sjakste T, Paramonova N, et al. Association of obesity
with proteasomal gene polymorphisms in children. J Obes. 2013;
2013:638154.
7. Sjakste T, Paramonova N, Wu LS-S, et al. PSMA6 (rs2277460,
rs1048990), PSMC6 (rs2295826, rs2295827) and PSMA3
(rs2348071) genetic diversity in Latvians, Lithuanians and Tai-
wanese. Meta Gene. 2014;2:283–98.
8. Sjakste T, Paramonova N, Rumba-Rozenfelde I, Trapina I, Sugo-
ka O, Sjakste N. Juvenile idiopathic arthritis subtype- and sex-spe-
cific associations with genetic variants in the PSMA6/PSMC6/
PSMA3 gene cluster. Pediatr Neonatol. 2014;55(5):393–403.
9. Hammer Q, Harper D, Ryan P. Past: Paleontological Statistics
software packarge for education and data analysis. Paleontolo-
gija Electronica. 2001; 4(1):9pp
10. Rozas J. DNA sequence polymorphism analysis using DnaSP.
Methods Mol Biol. 2009;537:337–50.
11. Lewis CM. Genetic association studies: design, analysis and in-
terpretation. Brief Bioinform. 2002;3(2):146–53.
12. Shi H, Jiang B, Wei Sim JD, Chum ZZ, Ali NB, Toh MH. Factors
associated with obesity: a case-control study of young adult Sin-
gaporean males. Mil Med. 2014;179(10):1158–65.
13. Bennet L, Lindblad U, Franks PW. A family history of diabetes
determines poorer glycaemic control and younger age of diabe-
tes onset in immigrants from the Middle East compared with na-
tive Swedes. Diabetes Metab. 2014. pii: S1262-3636(14)00136-0.
14. Benjamin AM, Suchindran S, Pearce K, et al. Gene by sex in-
teraction for measures of obesity in the framingham heart study.
J Obes. 2011;2011:329038.
15. Heid IM, Jackson AU, Randall JC, et al. Meta-analysis identifies
13 new loci associated with waist-hip ratio and reveals sexual
dimorphism in the genetic basis of fat distribution. Nat Genet.
2010;42(11):949–60.
16. Paramonova N, Wu L. Shi-Shin, Rumba-Rozenfelde I, Wang J-Y,
Sjakste N, Sjakste T. Genetic variants in the PSMA6, PSMC6 and
PSMA3 genes associated with childhood asthma in Latvian and
Taiwanese populations. Biopolym Cell. 2014; 30(5):377–87.
17. Kalnina J, Paramonova N, Sjakste N, Sjakste T. Study of asso-
ciation between polymorphisms in the PSMB5 (rs11543947) and
PSMA3 (rs2348071) genes and multiple sclerosis in Latvians.
Biopolym Cell. 2014; 30(4):305–9.
18. Kaufman F. Type 2 diabetes mellitus in children and adolescents:
the new epidemic. Obesity in Childhood and Adolescence. Eds
W. Keiss, C. Marcus, M. Wabitsch. New Jersey, Karger publ.,
2004: 183–4.
19. de Luca C, Olefsky JM. Stressed out about obesity and insulin re-
sistance. Nat Med. 2006;12(1):41–2.
Received 01.10.14
480
PARAMONOVA N. ET AL.
|