Azabu University Science Information Repository / 麻布大学学術情報リポジトリ
Not a member yet
1842 research outputs found
Sort by
Reference intervals for echocardiographic measurements in healthy Chihuahua dogs
Get PDFChihuahuas are one of the most common small breed dogs in Japan, and this breed is known to be predisposed to myxomatous mitral valve disease (MMVD). Echocardiographic assessment is essential for definitive diagnosis of MMVD in dogs as well as determining the stage. Because the Chihuahua's body size is the smallest among the dog breeds and the widely used echocardiographic reference range is established on the basis of larger dogs, it is unclear whether the existing reference range can be applied to the Chihuahua breed as well. Therefore, this study aimed to determine an echocardiographic reference range for Chihuahua dogs. The left atrial short-axis diameter (LA), aortic valve short-axis diameter, interventricular septum thickness at end-diastole, left ventricular internal dimension at end-diastole (LVIDd), and left ventricular posterior wall thickness at end-diastole from 47 healthy Chihuahuas were analyzed. These parameters increased logarithmically as body weight increased. Furthermore, LA and LVIDd were within the previously established reference range generated primarily from multiple breeds of moderate to large breed dogs.journal articl
Identification of genes associated with human-canine communication in canine evolution
Get PDFThe dog (Canis familiaris) was the first domesticated animal and hundreds of breeds exist today. During domestication, dogs experienced strong selection for temperament, behaviour, and cognitive ability. However, the genetic basis of these abilities is not well-understood. We focused on ancient dog breeds to investigate breed-related differences in social cognitive abilities. In a problem-solving task, ancient breeds showed a lower tendency to look back at humans than other European breeds. In a two-way object choice task, they showed no differences in correct response rate or ability to read human communicative gestures. We examined gene polymorphisms in oxytocin, oxytocin receptor, melanocortin 2 receptor, and a Williams–Beuren syndrome-related gene (WBSCR17), as candidate genes of dog domestication. The single-nucleotide polymorphisms on melanocortin 2 receptor were related to both tasks, while other polymorphisms were associated with the unsolvable task. This indicates that glucocorticoid functions are involved in the cognitive skills acquired during dog domestication.journal articl
Comparison of the effects of two commercially available prescription diet regimens on the fecal microbiomes of client-owned healthy pet dogs
Get PDFIn the present study, we used next-generation sequencing to investigate the impacts of two commercially available prescription diet regimens on the fecal microbiomes of eleven client-owned healthy pet dogs. We tested an anallergenic diet on 6 dogs and a low-fat diet on 5 dogs. Before starting the study, each dog was fed a different commercial diet over 5 weeks. After collecting pre-diet fecal samples, the anallergenic or low-fat diet was administered for 5 weeks. We then collected fecal samples and compared the pre- and post-diet fecal microbiomes. In the dogs on the anallergenic diet, we found significantly decreased proportions of Bacteroides, Ruminococcaceae, and Fusobacteriaceae, belonging to the phyla Bacteroidetes, Firmicutes, and Fusobacteria, respectively. The proportion of the genus Streptococcus belonging to the phylum Firmicutes was significantly increased upon administering the anallergenic diet. In the dogs on the low-fat diet, although the phyla Actinobacteria and Bacteroidetes tended to increase (p=0.116) and decrease (p=0.147) relative to the pre-diet levels, respectively, there were no significant differences in the proportions of any phylum between the pre- and post-diet fecal microbiomes. The anallergenic diet induced a significantly lower diversity index value than that found in the pre-diet period. Principal coordinate analysis based on unweighted UniFrac distance matrices revealed separation between the pre- and post-diet microbiomes in the dogs on the anallergenic diet. These results suggest that, even in pet dogs kept indoors in different living environments, unification of the diet induces apparent changes in the fecal microbiome.journal articl
Circadian rhythms of the mRNA abundances of clock genes and glucose transporters in the jejunum of weanling-growing pigs
Get PDFBackground
Whether abundance of glucose transporter mRNAs in the small intestine of pigs shows circadian rhythms and its regulation by clock genes was still unknown.
Objectives
We examined whether the abundance of glucose transporters and clock genes mRNAs in the small intestine of pigs shows circadian rhythms.
Methods
Twenty barrows (4 weeks old) were reared under 12 h bright and 12 h dark lighting conditions. During the 3-week feeding trial, pigs were allowed free access to feed. The abundances of the mRNA of glucose transporters (SGLT1 and GLUT2) and clock genes (Bmal1, Per1, Per2, and Cry2) in the intestine were measured at four time points (ZT2, ZT8, ZT14, and ZT20).
Results
In the jejunum, the abundance of SGLT1 mRNA was higher at ZT20 and ZT2 and lower at ZT8 and ZT14 (p < 0.05). The abundances of GLUT2 mRNA in the jejunum at ZTs 20 and 2 were tended to be higher than those at ZTs 8 and 14 (p = 0.05). In the jejunum, the abundance of Bmal1 mRNA was higher at ZT8 and ZT14 than at ZT20 and ZT2 (p < 0.05). Further, the abundance of Per1 mRNA at ZT2 was higher than those at the other sampling times (p < 0.05). The abundance of Per1 mRNA at ZT8 was higher than that at ZT14 (p < 0.05), while that of Per2 mRNA was higher at ZT2 than those at ZTs 20 and 14 (p < 0.05).
Conclusion
We speculate that these circadian rhythms of abundances of glucose transporter mRNAs are regulated by the clock genes expressed in the jejunum.journal articl
What is the Future “Mini Livestock”?:Investigation of Promising Farmed Insect Species for Food And Feed
Get PDFP(論文)原著論文application/pdfORIGINAL ARTICLEdepartmental bulletin pape
Association between MTHFR haplotype and alcohol dependence in Japanese
Get PDF麻布大学博士(学術)[Introduction]
Alcohol addiction is a drug addiction involving physical and psychological dependence on alcohol. It is said to exhibit multifactorial inheritance and is thought to have a heritability incidence of 50% to 60%.
Methylenetetrahydrofolate reductase (MTHFR) catalyzes the irreversible reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, and plays a useful role in the methylation of homocysteine to methionine. Abnormal DNA methylation due to deletion of the MTHFR gene may affect gene regulation, and it is known that it alters the dopaminergic neurotransmitter system in the brain, and affects cognitive behavior and addiction. Therefore, it is considered that a MTHFR gene mutation may indirectly affect the development of alcohol dependence. The MTHFR gene is located on chromosome 1p36.3, and C677T (rs1801133) located in exon 4 and A1298C (rs1801131) located in exon 7 are known as MTHFR gene polymorphisms. The T allele frequency of MTHFR gene polymorphism C677T has been reported to be significantly higher in male alcohol-dependent patients, and single nucleotide polymorphisms (SNPs) located on the MTHFR gene may be involved in the vulnerability to the onset of this disease.
So far, no studies have been conducted on Japanese subjects regarding the relationship between C677T and alcohol dependence. Also, the relationship with A1298C has not been investigated in other populations.
In this study, we compared the frequency of MTHFR polymorphisms between alcohol-dependent patients and healthy controls, and also performed haplotype analysis to clarify the genetic factors for alcohol dependence formation.
Furthermore, in order to investigate the effect of MTHFR gene polymorphisms on alcohol dependence in more detail, we examined a group of alcoholics with ALDH2*1/*1 who are said to be prone to addiction due to high alcohol metabolism. A comparative analysis with healthy subjects was also performed.
[Materials and Methods]
The subjects in this study were 64 patients (male: 57, female: 7) with a diagnosis of alcohol dependence according to DSM-IV criteria and 73 unrelated healthy people (male: 22, female: 51).
There was no significant difference in age between the two groups. Blood samples were collected and all subjects provided written informed consent for genetic studies. The study was approved by the ethics committee of Azabu University.
MTHFR and ALDH2 polymorphisms were genotyped by means of the polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method according to Frosst, Weisberg and Wu. The PCR products were digested with restrictive enzymes NinfI and MboII, and the digested products were subjected to electrophoresis on a polyacrylamide gel and then visualized using the ethidium bromide staining method.
The MTHFR polymorphism difference between the patients with alcohol dependence and healthy control subjects were assessed using the χ2 test or Yates’ correction. In addition, linkage disequilibrium (LD) coefficients (D’ and r2) and haplotype frequencies were calculated with gPLINK 2.050 (http://pngu.mgh.harvard.edu/purcell/plink/) and Haploview 4.2 (http://www.broad.mit.edu/mpg/haploview/index.php) respectively. Statistical significance was defined as p < 0.05.
[Results]
It was shown that the genotypic and allelic frequencies of rs1801133 polymorphisms were not associated with alcohol dependence. For A1298C, there was no significant difference in genotype frequency, but there was a significant trend toward a difference in allele frequency in the χ2 test after Yates' correction (χ2 (1) = 3.57, p = 0.0589), with the C allele appearing more frequently in the alcoholic patient group.
A comparative analysis of subjects carrying the ALDH2 gene polymorphism *1/*1 showed no significant difference in genotype frequency of A1298C. However, a significant difference was found in allele frequency (χ2 (1) = 7.66, p = 0.00566), with the C allele appearing significantly more frequently in the alcohol patient group.
There are four haplotypes involving combinations of alleles on the same chromosome, and haplotype analysis of the two SNPs showed a significant higher frequency of haplotype 2（C677 -1298C）in alcoholics with ALDH2 *1/*1 than in controls with ALDH2 *1/*1 (p = 0.00697).
The index values indicating the correlation between C677T and A1298C were D' = 0.708 and r 2 = 0.103, which indicated no linkage disequilibrium.
[Discussion]
This study suggested that on MTHFR gene haplotypes (C-C) may be related to alcohol dependence.
The relationship between MTHFR gene polymorphisms haplotypes and the development of alcohol dependence was investigated using the genetic background of alcohol sensitivity (ALDH2 *1/*1). As a result, four haplotypes involving combinations of alleles on the same chromosome were found, and haplotype analysis of the two SNPs showed a significantly higher frequency of haplotype 2 (C677 -1298C) in alcoholics with ALDH2 *1/*1 than in controls with ALDH2 *1/*1 (p = 0.00697). In a comparative analysis between an alcoholic patient group with ALDH2 gene polymorphism *1/*1 (wild type; non flasher) and a healthy subject group, significant differences were observed in the haplotype frequency between the two polymorphisms and the C-C haplotype. The frequency was significantly higher in the alcoholics group (χ2 (3) = 8.02, global p = 0.0456).
It has been reported that the frequency of T allele occurrence of MTHFR gene polymorphism C677T is significantly higher in alcoholics. H Singh. et al. reported that the T allele of MTHFR gene polymorphism C677T may exacerbate adverse health risks in the future among drinkers. Based on this study, we hypothesize that these alleles may be some of the risk factors for the development of alcohol dependence, but the results show no significant association. Several studies on C677T and alcoholism have been conducted so far, but consistent results have not been obtained. One of the reasons for this is thought to be the difference in the frequencies of alleles between races. The frequencies of occurrence of alleles vary depending on the geographical region and ethnicity. According to the results of this study, the frequency of occurrence of alleles in healthy Japanese subjects is 42.5%. It is reported that it is 24.1% to 64.3% in the most European countries and 0.0% in the least African countries. However, the frequency of occurrence of alleles determined from a database (dbSNP https://www.ncbi.nlm.nih.gov/snp/rs1801131#frequency_tab) was 34.9% in Europe and 12.1% in Africa. Such differences in distribution are thought to be due to the environment surrounding alcohol, and racial differences (white and colored races).
It has been reported that the 677TT genotype frequency is lower in a alcohol-dependent patient group than in a healthy subject group, suggesting that the 677TT genotype plays a protective role against alcohol dependence. On the other hand, there are reports that the 677TT genotype frequency is slightly higher in a group of alcoholics, and it is necessary to further study whether the 677TT genotype has a protective role against alcohol dependence. No studies have been conducted on the association between A1298C and alcoholism, but studies on esophageal cancer, gastric cancer, pancreatic cancer, and colorectal cancer have been conducted. In a study involving colorectal cancer, the 1298CC genotype was associated with a significant increase statistically in the risk of colorectal cancer in individuals with high alcohol consumption. Our results showed that the C allele frequency was significantly higher in the alcohol-dependent group than in the healthy group, suggesting that it may be involved in the vulnerability to alcohol dependence. In addition, no linkage was found between C677T and A1298C in the linkage disequilibrium analysis in this study. Therefore, it is considered difficult to use one of them as a tag SNP as a substitute for genotyping, although the C677T allele and the A1298C allele have the ability to reduce MTHFR activity.
Furthermore, on haplotype analysis, a significant difference was found between the alcohol-dependent patient group consisting of four types of haplotypes and ALDH2 gene polymorphism *1/*1 and the healthy subject group. Haplotype C-C occurred more frequently in the alcohol-dependent group than in the healthy group (χ2 (1) = 7.28, global p = 0.00697). The MTHFR activities of the haplotypes are presumed to be high activity C-A, medium activity C-C and T-A, and low activity T-C, respectively. The high frequency of occurrence of moderately active haplotype C-C in this study indicates that the C-C linkage of MTHFR gene polymorphisms rs1801133 and rs1801131 causes alcohol dependence in individuals with ALDH2 *1/*1. However, it is unclear from this study alone whether MTHFR activity is involved in the vulnerability to addiction development.【はじめに】
アルコール依存症は、アルコールに対する身体的及び心理的依存の薬物中毒の一形態である。また、多因子遺伝によって引き起こされる可能性もあり、50%〜60%の遺伝率を有すると考えられている。
メチレンテトラヒドロ葉酸還元酵素（MTHFR）は、5,10-メチレンテトラヒドロ葉酸の5-メチルテトラヒドロ葉酸への不可逆的な還元を触媒し、ホモシステインからメチオニンへのメチル化に有用な役割を果たす。MTHFR遺伝子の欠損によるDNAメチル化の異常は、遺伝子調節に影響を与える可能性があり、脳のドーパミン作動性神経伝達システムを変化させ、認知行動と依存症に影響を与えることが知られている。このことからMTHFR遺伝子変異はアルコール依存症の発生に間接的に影響を与える可能性があると考えられている。MTHFR遺伝子は染色体1p36.3に存在し、MTHFR遺伝子多型としてエクソン4に位置するC677T（rs1801133） やエクソン7に位置するA1298C （rs1801131） が知られている。MTHFR遺伝子多型C677TのT allele頻度は男性のアルコール依存症患者において、有意に高いことが報告されておりMTHFR遺伝子上に位置する一塩基多型（SNP）が本疾患発症の脆弱性に関与する可能性がある。これまでにC677Tとアルコール依存症との関連性についての検討は日本人を対象とした研究は行われていない。また、A1298Cとの関連性については、他集団においても検討されていない。
本研究では、アルコール依存形成の遺伝子要因解明の一助として、MTHFR遺伝子多型頻度をアルコール依存症患者群と健常者群間で比較し、ハプロタイプ解析も行い検討した。
さらにMTHFR遺伝子多型の影響についてより詳細に検討するため、アルコール代謝が強く依存症になりやすいといわれるALDH2*1 /*1を有するアルコール依存症患者群及び健常者群間の比較解析も行った。
【対象と方法】
書面においてインフォームド・コンセントの得られたDSM-IVの診断基準において精神保健指定医によりアルコール依存症と診断されたアルコール依存症患者64人（男性57人；女性7人）、アルコール依存経歴または家族歴のない健常者73人（男性22人；女性51人）を対象とした。これらの対象者から採血を行い、指定された管理者において匿名化を行った。患者群の発症時の年齢と健常者群の年齢で有意差はなかった。本研究は麻布大学ヒトゲノム・遺伝子解析研究に関する倫理審査委員会の承認を得て行った。
ゲノムDNAは、フェノール・クロロホルム法により抽出・精製し、MTHFR遺伝子多型C677T、A1298Cの解析は、Frosstら、Weisbergらの方法に従いPolymorphism Chain Reaction（PCR）- Restriction Fragment Length Polymorphism（RFLP）法により、それぞれ制限酵素Hinf I（New England BioLabs）、Mbo II（New England BioLabs）を用いて行った。ALDH2遺伝子多型の解析は、Wuらの方法に従いPCR-RFLP法により制限酵素Mbo II（New England BioLabs）を用いて行った。
統計学的解析は、アルコール依存症患者群と健常者群において、上記2つのMTHFR遺伝子多型の遺伝子型及び対立遺伝子頻度に差があるかどうか検討するためにχ2検定及びYatesの補正を行った。また、連鎖不平衡及びハプロタイプ解析にgPLINK v. 2.050とHaploview v. 4.2を用いた。有意水準はp < 0.05とした。
【結果】
C677Tでは両群との間で、遺伝子型及び対立遺伝子頻度に有意な差は認められなかった。また、A1298Cでは遺伝子型頻度に有意な差は認められなかったが、Yatesの補正後のχ2検定において対立遺伝子頻度の差に有意な傾向が見られ（χ2 (1) = 3.57, p = 0.0589）、C alleleがアルコール依存症患者群で出現頻度が高かった。
また、ALDH2遺伝子多型*1/*1を保持している被検者を対象とした比較解析を行ったところ、A1298Cの遺伝子型頻度に有意な差は認められなかった。しかし、対立遺伝子頻度においては有意な差が認められ（χ2 (1) = 7.66, p = 0.00566）、アルコール患者群でC alleleの出現頻度が有意に高かった。
同一染色体上の対立遺伝子の組み合わせからなるハプロタイプは4種類存在し、ALDH2遺伝子多型*1/*1を保持している被験者を対象とした比較解析では、有意な差が認められ（χ2 (3) = 8.02, global p = 0.0456）、アルコール依存症患者群でハプロタイプC-Cの出現頻度が有意に高かった（χ2 (1) = 7.28, p = 0.00697）。C677TとA1298Cの相関を示す指標値はD' = 0.708、r 2 = 0.103であり、連鎖不平衡を示さなかった（D' およびr 2は連鎖不平衡係数であり、0～1の数値で表される。D' は連鎖の程度、r 2は連鎖の強さを示す。）
【考察】
今回の研究では、MTHFR遺伝子多型とアルコール依存症発生との関係をアルコール感受性の遺伝的背景（ALDH2 *1/*1）も揃えて検討した。C677T多型では遺伝子型及び対立遺伝子頻度に差は見られなかったが、A1298C多型では活性の低いC型で出現頻度が高く、さらに、ALDH2遺伝子多型*1/*1（wild type; non flasher）を持つアルコール依存症患者群と健常者群との比較解析において両多型間のハプロタイプ頻度に有意な差が認められ、C-Cハプロタイプの頻度がアルコール依存症患者群で有意に高かった（χ2 (3) = 8.02, global p = 0.0456）。
MTHFR遺伝子多型C677TのT allele出現頻度はアルコール依存症患者において、有意に高いことが報告されている。Singh, H.らはMTHFR遺伝子多型C677TのT alleleが飲酒者の間で将来的に健康リスクを悪化させる可能性があることを指摘している。今回、我々はこの対立遺伝子がアルコール依存症発症のリスクファクターの一つではないかという仮説を立てたが、今回の結果では有意な関連は認められなかった。これまでにC677Tとアルコール依存症との研究はいくつか行われているが一貫した結果は得られていない。この理由の1つとしては、人種間における対立遺伝子頻度の違いが起因していると考えられている。T allele出現頻度は、地理的領域間及び民族の違いにより変動し、今回の研究結果では日本人の健常者でのT allele出現頻度は42.5%であった一方で最も多いヨーロッパ諸国では24.1％から64.3％、最も少ないアフリカ諸国では0.0%であることが報告されている。なお、データベース（dbSNP https://www.ncbi.nlm.nih.gov/snp/rs1801131#frequency_tab）から習得したT allele出現頻度はヨーロッパで34.9%、アフリカで12.1%であった。このよう分布の違いはアルコールを取り巻く環境や人種差（白人や有色人種）に起因すると考えられる。
また、677TT遺伝子型頻度はアルコール依存症患者群において健常者群と比較し低いことが報告されており、677TT遺伝子型はアルコール依存症に対して保護的な役割を果たすことを示唆している。その一方で677TT遺伝子型がアルコール依存症患者群においてわずかに高いという報告も存在し677TT遺伝子型がアルコール依存症に対して保護的役割があるかはさらなる関連研究が必要だと考える。
A1298Cとアルコール依存症との関連研究はこれまで行われていなかったが、食道癌、胃癌、膵臓癌、並びに大腸癌における研究は行われている。大腸癌との関連研究では1298CC遺伝子型は、アルコール消費量が高かった個体では統計的大腸がんの危険性の有意な増加と関連している。今回の我々の解析結果からC alleleが健常者群よりアルコール依存患者群で有意に高値を示したことから、アルコール依存症への脆弱性に関与する可能性が示唆された。
本研究の連鎖不平衡解析においてC677TとA1298Cに連鎖関係は認められなかった。したがって、C677TのT allele及びA1298CのC alleleはMTHFR活性を低下させる機能を有するが、一方をタグSNPとして遺伝型判定の代用に用いることは難しいと考えられる。
さらにハプロタイプ解析の結果、4種類からなるハプロタイプとALDH2遺伝子多型*1/*1のアルコール依存症患者群と健常者群間において有意差を認めた。アルコール依存症患者群は健常者群と比較しハプロタイプC-Cの出現頻度が高かった（χ2 (1) = 7.28, global p = 0.00697）。各ハプロタイプのMTHFR活性は高活性C-A、中活性C-C及びT-A、低活性T-Cと推定される。本研究で中活性のハプロタイプC-Cが高い出現頻度を示したことは、ALDH2遺伝子多型*1/*1の遺伝子を持つ個体にとってMTHFRの遺伝子多型rs1801133とrs1801131のC-C連鎖がアルコール依存症発症に関与している可能性を示唆する。ただし、MTHFR活性が依存症発症の脆弱性に関与しているのかはこの研究だけでは不明である。
結論として、本研究ではMTHFR遺伝子多型は、特にアルコール（アセトアルデヒド）代謝活性が強く飲酒量が増えやすいといわれるALDH2*１/*1を持つ個体はC677T（rs1801133）のC alleleを持ちA1298C（rs1801131）のC alleleを持つ個体に、アルコール依存症が発症しやすいのではないかということを指摘した。doctoral thesi
Association between irregular daily routine and risk of incident stroke and coronary heart disease in a large Japanese population
Get PDFCircadian misalignments have been linked to adverse cardiometabolic outcomes. However, the association between irregular daily routine and the risk of cardiovascular disease (CVD) remains unknown. We examined this association in a prospective study in Japan. The study included 78,115 Japanese participants aged 45–74 years. The self-reported daily routine was evaluated using the question, ‘Is your daily routine or activity schedule regular?’ The response (yes/no) was obtained as a binary variable. Cox proportional hazard regression analysis was used to estimate the hazard ratios and 95% confidence intervals for the association between an irregular daily routine and CVD incidence risk. Among the participants, 23.7% reported an irregular daily routine. During the mean follow-up period of 13.3 years, we observed 4641 CVD events. An irregular daily routine was significantly associated with increased risks of CVD and total stroke in women, but not in men. This positive association between an irregular daily routine and the risk of CVD was weak in the high vegetable and fruit consuming population. An irregular daily routine is positively associated with the risk of incident CVD, especially in women. These associations may be weak in populations that consume a diet rich in vegetables and fruits.journal articl
Effects of combined one-lung ventilation and intrathoracic carbon dioxide insufflation on intrathoracic working space when performing thoracoscopy in dogs
Get PDFOBJECTIVE
To evaluate the effects of combining one-lung ventilation and carbon dioxide insufflation (OLV-CDI) on intrathoracic working space (determined by means of CT) during thoracoscopy in dogs and investigate conditions that could safely improve working space compared with OLV alone.
ANIMALS
6 healthy Beagles.
PROCEDURES
Dogs were anesthetized, and right- or left-sided (n = 3/side) OLV was instituted. On the blocked side, a laparoscopic trocar sleeve was placed in the ninth intercostal space for CDI. CT was performed under 3 conditions: with OLV alone, with OLV-CDI at an intrapleural pressure (IPP) of 3 mm Hg, and with OLV-CDI at an IPP of 5 mm Hg. Working space volume (WSV), ventilation space volume (VSV), and thoracic cavity volume (TCV) were determined from CT images.
RESULTS
With OLV-CDI at an IPP of 3 or 5 mm Hg, WSV and TCV were significantly increased, compared with values obtained during OLV alone. With OLV-CDI at an IPP of 5 mm Hg, VSV and Spo2 were significantly decreased, compared with values obtained during OLV alone. Additionally, contralateral pneumothorax was observed in 4 dogs at an IPP of 5 mm Hg.
CLINICAL RELEVANCE
Combining OLV and CDI could provide a larger working space than OLV alone, even with an IPP of 3 mm Hg, in dogs of limited size. However, an evaluation of the effects on oxygenation and cardiovascular variables is needed before clinical use.journal articl
Association between mu opioid receptorgene polymorphisms and alcohol dependence in a Japanese population
Get PDFAlcohol dependence is an addiction that causes psychological and physical dependence and makes it difficult for those affected to control their intake of alcohol. The μ (mu), δ (delta) and κ (kappa) opioid receptors are thought to be associated with the development of alcohol dependence. Research has shown that μ opioid receptor knockout mice exhibit reduced alcohol consumption and reduced preference for alcohol. In this study, we confirmed whether mu opioid receptor (OPRM1) polymorphisms (IVS2+691C/G, −172G/T and −1748G/A) indeed have an effect on alcohol dependence formation in 64 patients, with 73 healthy people used as a control group. We compared the genotype, allele, carrier (minor allele carriers versus major allele homozygous carriers) and haplotype frequencies between these groups. In addition, the 1510A allele of acetaldehyde dehydrogenase 2 (ALDH2) polymorphism (1510G/A) causes poor metabolism of acetaldehyde, a major metabolite of alcohol. We also focused on ALDH2 1510G/G (ALDH2 *1/*1) carriers in the subjects. Three OPRM1 and one ALDH2 genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. No significant differences were found in the frequency of OPRM1 polymorphisms between those suffering from alcohol dependence and the control group. We concluded that the three OPRM1 polymorphisms (IVS2+691C/G, −172G/T and −1748G/A) were not likely to be risk factors for alcohol dependence in a Japanese population. This report is the first in a Japanese population. Nevertheless, further analysis of the opioid receptor gene in a large sample size is required.アルコール依存症とは，飲酒の自制が困難となる薬物中毒であり，オピオイド受容体との関連が考えられている。μオピオイド受容体欠損マウスは，アルコール自己投与の減少とアルコールに対する嫌悪を示すことが確認されている。本研究では，μオピオイド受容体（OPRM1）遺伝子多型IVS2+691C/G，−172G/Tおよび −1748G/Aがアルコール依存形成に与える影響を調べるため，遺伝子型，アレルおよびマイナーアレル保持者別頻度，ハプロタイプ解析，連鎖不平衡解析を含めた検討を行った。なお，OPRM1遺伝子多型の影響についてより詳細に検討するため，アルコール感受性に関わる2型アルデヒド脱水素酵素遺伝子多型ALDH2 *1/*1を有する対象者に着目した解析も行った。アルコール依存症患者64人，コントロール75人を対象とした。遺伝子多型の解析には，制限酵素断片長多型法（PCR-RFLP）を用いた。解析の結果，患者群および健常者群間における遺伝子型，アレルおよびマイナーアレル保持者別，全てのハプロタイプ頻度において，有意な差異は認められなかった。今回の結果より，着目した3つのOPRM1遺伝子多型がアルコール依存症発症の危険因子となる可能性は低いことが示唆された。今後は，同遺伝子上の他の多型や，他のオピオイド受容体にも着目し，アルコール依存症との関与についてより詳細に検討する必要があると考えられる。journal articl