AIM： To investigate the frequency and distribution of /V-acetyltransferase 2 （NAT2） and uridine 5＇-diphosphate （UDP）-glucuronosyltransferase 1A7 （UGT1A7） genes in patients with ulcerative colitis （UC） and Cr...AIM： To investigate the frequency and distribution of /V-acetyltransferase 2 （NAT2） and uridine 5＇-diphosphate （UDP）-glucuronosyltransferase 1A7 （UGT1A7） genes in patients with ulcerative colitis （UC） and Crohn＇s disease （CD）. METHODS： Frequencies and distributions of IVAT2 and UGT1A7SNPs as well as their haplotypes were investigated in 95 patients with UC, 60 patients with CD, and 200 gender-matched, unrelated, healthy, control volunteers by PCR-restriction fragment length polymorphism （RFLP）, PCR-denaturing high-performance liquid chromatography （DHPLC）, and direct DNA sequencing. RESULTS： Multiple logistic regression analysis revealed that the frequency of haplotype, NAT2＊7B, significantly increased in CD patients, compared to that in controls （P= 0.0130, OR = 2.802, 95%CI = 1.243-6.316）. However, there was no association between NAT2 haplotypes and UC, or between any UGT1A7haplotypes and inflammatory bowel disease （IBD）. CONCLUSION： It is likely that the NAT2 gene is one ofthe determinants for CD in Japanese. Alternatively, a new CD determinant may exist in the 8p22 region, where NAT2 is located.展开更多
AIM: To identify whether the polymorphisms of the Nacetyltransferase (NAT) genes are susceptible to primary liver cancer (PLC) in Luoyang, a PLC low-incidence area of China.METHODS: The NAT1 and NAT2 genotypes of 96 P...AIM: To identify whether the polymorphisms of the Nacetyltransferase (NAT) genes are susceptible to primary liver cancer (PLC) in Luoyang, a PLC low-incidence area of China.METHODS: The NAT1 and NAT2 genotypes of 96 PLC cases and 173 controls were determined by PCR-RFLP.Both interaction between NAT1 or NAT2 and environmental risk factors were analyzed based on case control study.RESULTS: Compared to the control group, the frequencies of alleles NAT1*3, NAT1*4, NAT1*10, NAT1*14B and alleles NAT2*4, NAT2*6, NAT2*7 in PLC group showed no statistically significant difference (x2 = 2.61 and 4.16,respectively, both P＞0.05). The frequencies of NAT1 genotypes NAT1*3/*3, NAT1*3/*4, NAT1*3/*10,NAT1*3/*14B, NAT1*4/*4, NAT1*4/*10, NAT1*4/*14B,NAT1*10/*10, NAT1*10/*14B, and NAT2 genotypes NAT2*4/*4, NAT2*4/*6, NAT2*4/*7, NAT2*6/*6,NAT2*6/*7 and NAT2*7/*7 also had no statistically significant difference between the two groups (x2 = 11.86 and 2.94respectively both, P＞0.05). Neither the frequencies of rapid and slow NAT1 acetylators nor the frequencies of rapid and slow NAT2 acetylators were significantly different between the two groups (x2 = 0.598 and 0.44,respectively, both P＞0.05). The interaction betweenNAT1*10 and occupational exposures was found significant with an odds ratio of 3.40 (x2 = 8.42, P = 0.004,OR 95%CI:1.03-11.22). But no interaction was found between NAT2 and any environmental risk factors.CONCLUSION: The polymorphisms of NAT1 and NAT2are not susceptible to PLC in Luoyang. Allele NAT1*10interacts with occupational exposures.展开更多
Arylalkylamine N-acetyltransferase(aaNAT),considered a potential new insecticide target,catalyzes the acetylation of arylalkylamine substrates such as serotonin and dopamine and,hence,mediates diverse functions in ins...Arylalkylamine N-acetyltransferase(aaNAT),considered a potential new insecticide target,catalyzes the acetylation of arylalkylamine substrates such as serotonin and dopamine and,hence,mediates diverse functions in insects.However,the origin of insect aaNATs(iaaNATs)and the evolutionary process that generates multiple aaNATs in mosquitoes remain largely unknown.Here,we have analyzed the genomes of 33 species to explore and expand our understanding of the molecular evolution of this gene family in detail.We show that aaNAT orthologs are present in Bacteria,Cephalochordata,Chondrichthyes,Cnidaria,Crustacea,Mammalia,Placozoa,and Teleoste,as well as those from a number of insects,but are absent in some species of Annelida,Echinozoa,and Mollusca as well as Arachnida.Particularly,more than 10 aaNATs were detected in the Culicinae subfamily of mosquitoes.Molecular evolutionary analysis of aaNAT/aaNAT-like genes in mosquitoes reveals that tandem duplication events led to gene expansion in the Culicinae subfamily of mosquitoes more than 190 million years ago.Further selection analysis demonstrates that mosquito aaNATs evolved under strongly positive pressures that generated functional diversity following gene duplication events.Overall,this study may provide novel insights into the molecular evolution of the aaNAT family in mosquitoes.展开更多
AIM: To study the loss of heterozygosity (LOH) at 8p21-23 locus in diffuse gastric cancer.METHODS: To evaluate the involvement of this region in gastric cancer, we used eight microsatellite markers covering two Mb of ...AIM: To study the loss of heterozygosity (LOH) at 8p21-23 locus in diffuse gastric cancer.METHODS: To evaluate the involvement of this region in gastric cancer, we used eight microsatellite markers covering two Mb of mentioned region, to perform a high-resolution analysis of allele loss in 42 cases of late diffuse gastric adenocarcinoma.RESULTS: Six of these STS makers: D8S1149, D8S1645, D8S1643, D8S1508, D8S1591, and D8S1145 showed 36%, 28%, 37%, 41%, 44% and 53% LOH, respectively.CONCLUSION: A critical region of loss, close to the NAT2 locus and relatively far from FEZ1 gene currently postulated as tumor suppressor gene in this region.展开更多
Arylalkylamine N-acetyltransferase(aaNAT)catalyzes the acetylation of dopamine,5-hydroxy-tryptamine,tryptamine,octopamine,norepinephrine and other ary-lalkylamines to form respective N-acetyl-arylalkylamines.Depending...Arylalkylamine N-acetyltransferase(aaNAT)catalyzes the acetylation of dopamine,5-hydroxy-tryptamine,tryptamine,octopamine,norepinephrine and other ary-lalkylamines to form respective N-acetyl-arylalkylamines.Depending on the products formed,aaNATs are involved in a variety of physiological functions.In the yellow fever mosquito,Aedes aegypti,a number of aaNATs and aaNAT-like proteins have been reported.However,the primary function of each individual aaNAT is yet to be identified.In this study we investigated the function of Ae.aegypti aaNAT 1(Ae-aaNATl)in cuticle pigmentation and development of morphology.Ae-aaNAT1 transcripts were detected at all stages of development with highest expressions after pupation and right before adult eclosion.Ae-aaNATl mutant mosquitoes generated using clustered regularly interspaced palindromic repeats(CRISPR)-CRISPR-associated protein 9 had no obvious effect on larval and pupal development.However,the mutant mosquitoes exhibited a roughened ex-oskeletal surface,darker cuticles,and color pattern changes suggesting that Ae-aaNAT1 plays a role in development of the morphology and pigmentation of Ae.aegypti adult cuticles.The mutant also showed less blood feeding efficiency and lower fecundity when compared with the wild-type.The mutation of Ae-aaNAT1 influenced expression of genes involved in cuticle formation.In summary,Ae-aaNAT1 mainly functions on cuticular pigmentation and also affects blood feeding efficiency and fecundity.展开更多
Differences in the metabolism of tyrosine between insects and mammals present an interesting example of molecular evolution. Both insects and mammals possess finetuned systems of enzymes to meet their specific demands...Differences in the metabolism of tyrosine between insects and mammals present an interesting example of molecular evolution. Both insects and mammals possess finetuned systems of enzymes to meet their specific demands for tyrosine metabolites; however, more homologous enzymes involved in tyrosine metabolism have emerged in many insect species. Without knowledge of modem genomics, one might suppose that mammals, which are generally more complex than insects and require tyrosine as a precur sor for important catecholamine neurotransmitters and for melanin, should possess more enzymes to control tyrosine metabolism. Therefore, the question of why insects actually possess more tyrosine metabolic enzymes is quite interesting. It has long been known that insects rely heavily on tyrosine metabolism for cuticle hardening and for innate immune responses, and these evolutionary constraints are likely the key answers to this question. In terms of melanogenesis, mammals also possess a high level of regulation; yet mam malian systems possess more mechanisms for detoxification whereas insects accelerate pathways like melanogenesis and therefore must bear increased oxidative pressure. Our research group has had the opportunity to characterize the structure and function of many key proteins involved in tyrosine metabolism from both insects and mammals. In this mini review we will give a brief overview of our research on tyrosine metabolic enzymes in the scope of an evolutionary perspective of mammals in comparison to insects.展开更多
文摘AIM： To investigate the frequency and distribution of /V-acetyltransferase 2 （NAT2） and uridine 5＇-diphosphate （UDP）-glucuronosyltransferase 1A7 （UGT1A7） genes in patients with ulcerative colitis （UC） and Crohn＇s disease （CD）. METHODS： Frequencies and distributions of IVAT2 and UGT1A7SNPs as well as their haplotypes were investigated in 95 patients with UC, 60 patients with CD, and 200 gender-matched, unrelated, healthy, control volunteers by PCR-restriction fragment length polymorphism （RFLP）, PCR-denaturing high-performance liquid chromatography （DHPLC）, and direct DNA sequencing. RESULTS： Multiple logistic regression analysis revealed that the frequency of haplotype, NAT2＊7B, significantly increased in CD patients, compared to that in controls （P= 0.0130, OR = 2.802, 95%CI = 1.243-6.316）. However, there was no association between NAT2 haplotypes and UC, or between any UGT1A7haplotypes and inflammatory bowel disease （IBD）. CONCLUSION： It is likely that the NAT2 gene is one ofthe determinants for CD in Japanese. Alternatively, a new CD determinant may exist in the 8p22 region, where NAT2 is located.
基金Supported by the National Natural Science Foundation of China,No. 39870654
文摘AIM: To identify whether the polymorphisms of the Nacetyltransferase (NAT) genes are susceptible to primary liver cancer (PLC) in Luoyang, a PLC low-incidence area of China.METHODS: The NAT1 and NAT2 genotypes of 96 PLC cases and 173 controls were determined by PCR-RFLP.Both interaction between NAT1 or NAT2 and environmental risk factors were analyzed based on case control study.RESULTS: Compared to the control group, the frequencies of alleles NAT1*3, NAT1*4, NAT1*10, NAT1*14B and alleles NAT2*4, NAT2*6, NAT2*7 in PLC group showed no statistically significant difference (x2 = 2.61 and 4.16,respectively, both P＞0.05). The frequencies of NAT1 genotypes NAT1*3/*3, NAT1*3/*4, NAT1*3/*10,NAT1*3/*14B, NAT1*4/*4, NAT1*4/*10, NAT1*4/*14B,NAT1*10/*10, NAT1*10/*14B, and NAT2 genotypes NAT2*4/*4, NAT2*4/*6, NAT2*4/*7, NAT2*6/*6,NAT2*6/*7 and NAT2*7/*7 also had no statistically significant difference between the two groups (x2 = 11.86 and 2.94respectively both, P＞0.05). Neither the frequencies of rapid and slow NAT1 acetylators nor the frequencies of rapid and slow NAT2 acetylators were significantly different between the two groups (x2 = 0.598 and 0.44,respectively, both P＞0.05). The interaction betweenNAT1*10 and occupational exposures was found significant with an odds ratio of 3.40 (x2 = 8.42, P = 0.004,OR 95%CI:1.03-11.22). But no interaction was found between NAT2 and any environmental risk factors.CONCLUSION: The polymorphisms of NAT1 and NAT2are not susceptible to PLC in Luoyang. Allele NAT1*10interacts with occupational exposures.
基金supported by the National Natural Science Foundation of China(31860702 and 31960703)by the Hainan Province Science and Technology Special Fund(ZDKJ2021035).
文摘Arylalkylamine N-acetyltransferase(aaNAT),considered a potential new insecticide target,catalyzes the acetylation of arylalkylamine substrates such as serotonin and dopamine and,hence,mediates diverse functions in insects.However,the origin of insect aaNATs(iaaNATs)and the evolutionary process that generates multiple aaNATs in mosquitoes remain largely unknown.Here,we have analyzed the genomes of 33 species to explore and expand our understanding of the molecular evolution of this gene family in detail.We show that aaNAT orthologs are present in Bacteria,Cephalochordata,Chondrichthyes,Cnidaria,Crustacea,Mammalia,Placozoa,and Teleoste,as well as those from a number of insects,but are absent in some species of Annelida,Echinozoa,and Mollusca as well as Arachnida.Particularly,more than 10 aaNATs were detected in the Culicinae subfamily of mosquitoes.Molecular evolutionary analysis of aaNAT/aaNAT-like genes in mosquitoes reveals that tandem duplication events led to gene expansion in the Culicinae subfamily of mosquitoes more than 190 million years ago.Further selection analysis demonstrates that mosquito aaNATs evolved under strongly positive pressures that generated functional diversity following gene duplication events.Overall,this study may provide novel insights into the molecular evolution of the aaNAT family in mosquitoes.
基金This work was supported by the National Natural Science Foundation of China (No.30170295) Medical Developmental Foun- dation of Soochow University (No.EE134031)Young Teacher's Research Foundation of Soochow University (No.Q3134044)
基金Supported by Research Center of Gastric and Liver Disease in Tehran Taleghani hospital
文摘AIM: To study the loss of heterozygosity (LOH) at 8p21-23 locus in diffuse gastric cancer.METHODS: To evaluate the involvement of this region in gastric cancer, we used eight microsatellite markers covering two Mb of mentioned region, to perform a high-resolution analysis of allele loss in 42 cases of late diffuse gastric adenocarcinoma.RESULTS: Six of these STS makers: D8S1149, D8S1645, D8S1643, D8S1508, D8S1591, and D8S1145 showed 36%, 28%, 37%, 41%, 44% and 53% LOH, respectively.CONCLUSION: A critical region of loss, close to the NAT2 locus and relatively far from FEZ1 gene currently postulated as tumor suppressor gene in this region.
基金supported by National Natural Science Foundation of China(3186070231960703)Postgraduate Innovation Research Project of General Higher Education in Hainan Province,China(Hyb2018-08).
文摘Arylalkylamine N-acetyltransferase(aaNAT)catalyzes the acetylation of dopamine,5-hydroxy-tryptamine,tryptamine,octopamine,norepinephrine and other ary-lalkylamines to form respective N-acetyl-arylalkylamines.Depending on the products formed,aaNATs are involved in a variety of physiological functions.In the yellow fever mosquito,Aedes aegypti,a number of aaNATs and aaNAT-like proteins have been reported.However,the primary function of each individual aaNAT is yet to be identified.In this study we investigated the function of Ae.aegypti aaNAT 1(Ae-aaNATl)in cuticle pigmentation and development of morphology.Ae-aaNAT1 transcripts were detected at all stages of development with highest expressions after pupation and right before adult eclosion.Ae-aaNATl mutant mosquitoes generated using clustered regularly interspaced palindromic repeats(CRISPR)-CRISPR-associated protein 9 had no obvious effect on larval and pupal development.However,the mutant mosquitoes exhibited a roughened ex-oskeletal surface,darker cuticles,and color pattern changes suggesting that Ae-aaNAT1 plays a role in development of the morphology and pigmentation of Ae.aegypti adult cuticles.The mutant also showed less blood feeding efficiency and lower fecundity when compared with the wild-type.The mutation of Ae-aaNAT1 influenced expression of genes involved in cuticle formation.In summary,Ae-aaNAT1 mainly functions on cuticular pigmentation and also affects blood feeding efficiency and fecundity.
文摘Differences in the metabolism of tyrosine between insects and mammals present an interesting example of molecular evolution. Both insects and mammals possess finetuned systems of enzymes to meet their specific demands for tyrosine metabolites; however, more homologous enzymes involved in tyrosine metabolism have emerged in many insect species. Without knowledge of modem genomics, one might suppose that mammals, which are generally more complex than insects and require tyrosine as a precur sor for important catecholamine neurotransmitters and for melanin, should possess more enzymes to control tyrosine metabolism. Therefore, the question of why insects actually possess more tyrosine metabolic enzymes is quite interesting. It has long been known that insects rely heavily on tyrosine metabolism for cuticle hardening and for innate immune responses, and these evolutionary constraints are likely the key answers to this question. In terms of melanogenesis, mammals also possess a high level of regulation; yet mam malian systems possess more mechanisms for detoxification whereas insects accelerate pathways like melanogenesis and therefore must bear increased oxidative pressure. Our research group has had the opportunity to characterize the structure and function of many key proteins involved in tyrosine metabolism from both insects and mammals. In this mini review we will give a brief overview of our research on tyrosine metabolic enzymes in the scope of an evolutionary perspective of mammals in comparison to insects.
