Elevated serum uric acid (SUA)—hyperuricemia—is caused by overproduction of urate or by its decreased renal and/or intestinal excretion. This disease, which is increasing in prevalence worldwide, is ...associated with both gout and metabolic diseases. Several studies have reported relationships between
apolipoprotein E
(
APOE
) haplotypes and SUA levels in humans; however, their results remain inconsistent. This prompted us to investigate the relationship between
APOE
polymorphisms and SUA levels. Our subjects were 5,272 Japanese men, premenopausal women, and postmenopausal women. Multiple linear regression analyses revealed the ε2 haplotype of
APOE
to be independently associated with higher SUA in men (
N
= 1,726) and postmenopausal women (
N
= 1,753), but not in premenopausal women (
N
= 1,793). In contrast, the ε4 haplotype was little related to SUA levels in each group. Moreover, to examine the effect of Apoe deficiency on SUA levels, we conducted animal experiments using
Apoe
knockout mice, which mimics ε2/ε2 carriers. We found that SUA levels in
Apoe
knockout mice were significantly higher than those in wild-type mice, which is consistent with the SUA-raising effect of the ε2 haplotype observed in our clinico-genetic analyses. Further analyses suggested that renal rather than intestinal underexcretion of urate could be involved in Apoe deficiency-related SUA increase. In conclusion, we successfully demonstrated that the ε2 haplotype, but not the ε4 haplotype, increases SUA levels. These findings will improve our understanding of genetic factors affecting SUA levels.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Gout is a common arthritis caused by elevated serum uric acid (SUA) levels. Here we investigated loci influencing SUA in a genome-wide meta-analysis with 121,745 Japanese subjects. We identified 8948 ...variants at 36 genomic loci (
<5 × 10
) including eight novel loci. Of these, missense variants of
and
were predicted to be damaging to the function of these proteins; another five loci-
,
,
,
, and
-are related to cell metabolism, proliferation, or oxidative stress; and the remaining locus,
, is unknown. We also identified 132 correlated genes whose expression levels are associated with SUA-increasing alleles. These genes are enriched for the UniProt transport term, suggesting the importance of transport-related genes in SUA regulation. Furthermore, trans-ethnic meta-analysis across our own meta-analysis and the Global Urate Genetics Consortium has revealed 15 more novel loci associated with SUA. Our findings provide insight into the pathogenesis, treatment, and prevention of hyperuricemia/gout.
The first ever genome-wide association study (GWAS) of clinically defined gout cases and asymptomatic hyperuricaemia (AHUA) controls was performed to identify novel gout loci that aggravate AHUA into ...gout.
We carried out a GWAS of 945 clinically defined gout cases and 1003 AHUA controls followed by 2 replication studies. In total, 2860 gout cases and 3149 AHUA controls (all Japanese men) were analysed. We also compared the ORs for each locus in the present GWAS (gout vs AHUA) with those in the previous GWAS (gout vs normouricaemia).
This new approach enabled us to identify two novel gout loci (rs7927466 of
and rs9952962 of
) and one suggestive locus (rs12980365 of
) at the genome-wide significance level (p<5.0×10
). The present study also identified the loci of
,
and
. One of them, rs671 of
, was identified as a gout locus by GWAS for the first time. Comparing ORs for each locus in the present versus the previous GWAS revealed three 'gout vs AHUA GWAS'-specific loci (
,
and
) to be clearly associated with mechanisms of gout development which distinctly differ from the known gout risk loci that basically elevate serum uric acid level.
This meta-analysis is the first to reveal the loci associated with crystal-induced inflammation, the last step in gout development that aggravates AHUA into gout. Our findings should help to elucidate the molecular mechanisms of gout development and assist the prevention of gout attacks in high-risk AHUA individuals.
Gout is a common arthritis caused by elevated serum uric acid (SUA) levels. Here we investigated loci influencing SUA in a genome-wide meta-analysis with 121,745 Japanese subjects. We identified 8948 ...variants at 36 genomic loci (P<5 × 10
) including eight novel loci. Of these, missense variants of SESN2 and PNPLA3 were predicted to be damaging to the function of these proteins; another five loci-TMEM18, TM4SF4, MXD3-LMAN2, PSORS1C1-PSORS1C2, and HNF4A-are related to cell metabolism, proliferation, or oxidative stress; and the remaining locus, LINC01578, is unknown. We also identified 132 correlated genes whose expression levels are associated with SUA-increasing alleles. These genes are enriched for the UniProt transport term, suggesting the importance of transport-related genes in SUA regulation. Furthermore, trans-ethnic meta-analysis across our own meta-analysis and the Global Urate Genetics Consortium has revealed 15 more novel loci associated with SUA. Our findings provide insight into the pathogenesis, treatment, and prevention of hyperuricemia/gout.
There is test method according to JIS A 4706:2000 for the evaluation of sound insulation of window sash, this gives only the performance for whole of sash, but not for partial sound leak which really ...make heavy influence on the sound insulation performance of a window sash. In this paper, leakage sound through the narrow gaps is played attention, the influences of narrow gaps that decreases sound insulation performance such as directivities, strength distributions and frequency characteristics of sound leakage are made clear by acoustical experiments using a particle velocity sensor. We expect that these data will be used to find out some method effective for the improvement on sound insulation performance of window sash.
窓サッシの遮音性能評価法にはJIS A 4706:2000 ...に従う試験方法があるが，これはサッシ全体としての性能の把握に留まり，窓サッシの遮音性能に大きな影響を及ぼす隙間の影響や特徴を把握することはできない。そこで本文ではその隙間からの漏洩音に着目し，漏洩音の強度分布や指向性·周波数特性等の特徴について細かく調べ，サッシの遮音性能を低下させる漏洩音の特性を明らかにする。また，粒子速度センサーを用いて漏洩音の強度を部位別あるいは方向別に把握することでサッシの構造的特徴と漏洩音の関係について考察し，窓サッシの遮音性能向上に有効な方法を見出す一助とする。
Psoriasis is an inflammatory disease associated with aberrant crosstalk between the epidermis and immune system. However, the role of Langerhans cells (LCs) in psoriasis remains controversial.
To ...elucidate whether LCs are functionally involved in the development of psoriasis using a mouse model.
Two lines of transgenic mice were used and crossed. They included K5.Stat3C, the psoriasis-model mouse and langerin DTR knock-in (KI) mouse. We performed immunofluorescence staining for LCs in psoriatic lesion of human and model mice. Flow cytometric analyses were performed to compare between dendritic cells (DCs) and LCs in the epidermis and skin-draining lymph nodes (sDLNs). To assess cytokine/chemokine expression in the skin lesion or primary cultured keratinocytes, we performed RT-PCR, microarray analysis or intracellular staining on the flow cytometer.
LCs were activated in psoriatic lesion of patients with psoriasis and K5.Stat3C mice. Compared with non-transgenic mice, K5.Stat3C mice constitutively showed an increased number of LCs in the sDLNs before psoriasis-like lesion developed. Stat3C transgenic keratinocytes expressed an elevated level of IL-1α. Psoriasis-like lesion in K5.Stat3C mice were attenuated in the absence of LCs, indicating that LCs were essential to the development of psoriasis-like lesion. Furthermore, we also recognized that epidermal LCs in psoriatic lesion of not only K5.Stat3C mice but also psoriasis patients produced IL-23.
Our study suggests that Stat3 activation in keratinocytes may impact on LC activation in situ via IL-1α stimulation, at least in part, and that their presence may be essential for the pathogenesis of psoriasis through producing IL-23.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Automated identification and quantification systems with gas chromatography-mass spectrometry (GC-MS) (i.e., AIQS-GC) are used as a simple and comprehensive method for screening chemicals existing in ...the environment and are expected to be useful for emergency surveys in the event of a disaster. However, reports on the potential of AIQS-GC in heavily contaminated samples (HCSs) are limited. In this study, the identification performance of AIQS-GC was confirmed by comparing the exact mass of the targets identified by AIQS-GC with the measured accurate mass using GC-quadrupole-time-of-flight MS (GC-QTofMS) and by employing firefighting wastewater as HCS. In HCS, the mass spectrum interference was determined to cause false positives. The GC-QTofMS method revealed the presence of false positives and the false rate of AIQS-GC in HCS. Herein, AIQS-GC showed high identification accuracy in a normal sample such as river water. Conversely, in HCS, AIQS-GC may lead to incorrect evaluations. The combination of AIQS-GC and support method using GC-QTofMS, which can avoid the false positive is extremely useful for the rapid and easy analysis of HCS.
•AIQS-GC would lead to incorrect evaluation in a heavily contaminated samples (HCS)-like disaster sample.•Identification performance of AIQS-GC was confirmed by comparing accurate mass with exact mass using GC-QTofMS.•It was confirmed that AIQS-GC caused the incorrect evaluation in HCS.•The support method by GC-QTofMS can avoid the incorrect evaluation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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