Biomedical subjects

M Emi

Publications and source records attributed to M Emi.

221 records · Page 13Linked to original sources

PubMedDate not supplied

Specific genomic alterations in rat renal cell carcinomas induced by N-ethyl-N-hydroxyethylnitrosamine.

To characterize genetic alterations occurring in renal tumorigenesis, EHEN-induced renal cell tumors were examined using restriction landmark genomic scanning (RLGS) analysis, an electrophoretic separation technique that detects gene amplifications and deletions. Comparison of DNAs from tumor against those from corresponding nontumorous kidney and/or EHEN-treated kidney without development of renal tumors yielded specific alterations in terms of both amplified and reduced DNA spots. Two amplified spots were detected only in renal cell tumors and an additional four spots were frequent in EHEN-treated kidneys. One reduced spot was common to all tumor samples, and another was frequently detected in the tumors analyzed but not in EHEN-treated kidneys. A subset of the altered spots thus appeared to be specific for EHEN-induced renal tumorigenesis.

Animals↗

PubMedDate not supplied

Three TNFalpha single nucleotide polymorphisms in the Japanese population.

BACKGROUND: Tumour necrosis factor-alpha (TNFalpha) is an essential regulator of immune responses and is implicated to relate to several types of disease susceptibilities. Population information on polymorphisms is essential for the study of genetic diseases. AIM: To obtain accurate information about single nucleotide polymorphisms (SNPs) in the TNFalpha gene in the Japanese population. SUBJECTS AND METHODS: The entire TNFalpha gene was screened for SNPs by directly sequencing 48 chromosomes derived from 24 unrelated Japanese individuals. Allele frequencies of each polymorphism were determined and compared with those previously reported in other populations. RESULTS: Three SNPs, -308G/A at nt -308, IVS1 + 125G/A at nt 492 and IVS3 + 104G/A at nt 1359 were observed, of which one (IVS3 + 104G/A at nt 1359) was novel. In addition, allele frequencies of -308G/A were remarkably different from those presented in the NCBI dbSNP, indicating a significant ethnic difference. CONCLUSIONS: The polymorphisms and allele frequencies obtained in this study will be useful for genetic studies of common diseases such as osteoporosis and rheumatoid arthritis in the Japanese population.

Alleles↗

PubMedDate not supplied

Association of a single nucleotide variant in the human tumour necrosis factor alpha promoter region with decreased bone mineral density.

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) has come to be regarded as a potential osteoporotic factor, because it has stimulatory effects on cells of the osteoclast lineage and has been implicated in the pathogenesis of bone loss associated with oestrogen deficiency. We recently described genetic linkage between the TNFalpha locus and human osteoporosis by sib-pair analysis. However, the molecular mechanism by which this locus regulates bone mineral density (BMD) remains unknown. AIM: We investigated whether the observed linkage reflects a sequence variation which might affect expression of the TNFalpha gene or alter the function of TNFalpha protein. SUBJECTS AND METHODS: We examined three single-nucleotide polymorphisms (SNPs) of the TNFalpha gene in a group of 390 postmenopausal Japanese women living in northern Japan. Minor-allele frequencies for the three SNPs (-1031C, -863A and -857T) in this population were 0.16, 0.13 and 0.20, respectively. RESULTS: Among the three SNPs examined, we observed a significant correlation only between the presence of a T allele at nt -1031 and decreased BMD, by analysis of variance. Among the three genotypic groups at nt -1031, mean BMD values were significantly higher in the T-negative genotype (C/C homozygotes; mean SD = 0.342 +/- 0.052 g cm(-2)), compared with T-positive genotypes (T/T homozygotes, 0.309 +/- 0.062 g cm(-2); p = 0.0253 and T/C heterozygotes, 0.305 +/- 0.062 g cm(-2); p = 0.0164). CONCLUSIONS: Given the lines of evidence from different genetic studies, we suggest that TNFalpha may play a role in pathogenesis of osteoporosis.

Aged↗

PubMedDate not supplied

Type III dyslipoproteinemia in patients heterozygous for familial hypercholesterolemia and apolipoprotein E2. Evidence for a gene-gene interaction.

In four large pedigrees with heterozygous familial hypercholesterolemia (FH) genetically linked to the low density lipoprotein receptor locus, we have observed a strong interaction between the presence of FH and a single apolipoprotein (apo) E2 allele, resulting in a markedly increased prevalence of type III dyslipoproteinemia (DLPIII). DLPIII was defined by chemical criteria. None of the patients with DLPIII had tuberous or palmar xanthomas characteristic of classically defined type III hyperlipoproteinemia. After exclusion of four persons with apo E 2-2 phenotype, there were 89 FH patients and 110 non-FH subjects. Definite DLPIII (defined as a very low density lipoprotein [VLDL] cholesterol to plasma triglyceride ratio greater than 0.30 with plasma triglycerides greater than or equal to 150 mg/dl) was present in 26% of 43 FH patients with a single E2 allele compared with only 3.4% of 29 non-FH subjects with an E2 allele (p = 0.003). To further characterize this interaction we performed a two-way analysis of covariance, after adjustment for age, sex, and body mass index, to test for any interaction between FH and the apo E loci. There was a statistically significant interaction between FH and the presence of a single E2 allele for the ratio of VLDL cholesterol to plasma triglycerides and for a newly derived estimate of beta-VLDL cholesterol concentration. Estimated beta-VLDL cholesterol level was strongly correlated with age in the subgroup with FH and an E2 allele but not in other subgroups. There was no difference in estimated beta-VLDL cholesterol between sexes. Correlation between estimated beta-VLDL cholesterol level and body mass index in persons older than 18 years was of only marginal significance and of similar magnitude in persons with or without an apo E2 allele. Present knowledge suggests that beta-VLDLs are highly atherogenic; if so, then a sizable subset of FH patients having at least one apo E2 allele and DLPIII may be at increased risk for premature coronary heart disease.

Adolescent↗

PubMedDate not supplied

Effects of three genetic loci in a pedigree with multiple lipoprotein phenotypes.

In the course of familial investigations of coronary artery disease, we identified an extended kinship in which several members were affected with type IIa hyperlipoproteinemia (HLPIIa), type III dyslipoproteinemia (DLPIII), or hypobetalipoproteinemia (HBLP). To study the genetic defects responsible for plasma lipoprotein abnormalities in this pedigree and to investigate the phenotypic effect of different genotypic combinations, we used molecular markers for apolipoprotein (apo) B, apo E, and the low density lipoprotein (LDL) receptor to characterize segregation at each locus. Linkage analysis showed that elevated LDL cholesterol levels and the HBLP phenotype were due to defects at the LDL receptor and the apo B loci, respectively. One pedigree member, who inherited both an LDL receptor allele linked with elevated LDL cholesterol levels and an apo B allele linked with HBLP, had a normal lipoprotein phenotype. Seven patients who simultaneously inherited the defective LDL receptor allele and one or two apo E2 alleles manifested DLPIII. The E2 alleles in this pedigree were shown by DNA sequence analysis to be the common E2 158 (arginine----cysteine) allele. These findings suggested a possible interaction between the abnormal LDL receptor and apo E2 alleles, resulting in the expression of DLPIII in the presence of a single copy of ago E2.

Adolescent↗