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Wild-type Homozygotes (wild-type + homozygote)
Selected AbstractsElectrochemical Genotyping by Using Two Ferrocene/Isoquinoline-Connected DNA Probes with Different Redox Potentials on a Single ElectrodeCHEMISTRY - A EUROPEAN JOURNAL, Issue 29 2009Reona Ikeda A single electrode: We describe an electrochemical single-nucleotide polymorphism genotyping protocol using a single electrode that is modified with a ferrocene/isoquinoline conjugate connected to DNA probes, which possess different redox potentials. Three types of zygotes (a wild-type homozygote, a mutant homozygote, and a heterozygote) were identified by a single square wave voltammetric measurement. [source] Genetic Repeat Polymorphism in the Regulating Region of CYP2E1: Frequency and Relationship With Enzymatic Activity in AlcoholicsALCOHOLISM, Issue 6 2001E. Plee-Gautier Background: Differences in the regulatory region of the CYP2E1 gene could be responsible for the interindividual variation in the cytochrome P-450 2E1 (CYP2E1) involved in ethanol oxidation. Recently, a polymorphic repeat sequence in the human gene was described between ,2178 and ,1945 base pairs. Its frequency seemed to vary among different ethnic populations, and it was suspected to be related to an increased inducibility to further ethanol intake. In the study reported here, the frequency of this polymorphism was investigated in a white French population. Its relationship with the previously described Pst I/Rsa I or Dra I CYP2E1 polymorphisms, alcoholism, alcoholic liver disease, and inducibility of CYP2E1 by ethanol was examined. Methods: The polymorphic region was characterized by polymerase chain reaction in 103 controls, 148 alcoholic subjects without liver diseases, and 98 others with liver cirrhosis. By using in vivo chlorzoxazone (CHZ) metabolism, CYP2E1 phenotype was assessed in 36 non,ethanol-induced subjects (17 controls and 19 withdrawn alcoholics) and in 14 ethanol-induced subjects (10 controls after ingestion of 0.8 g/kg ethanol and four alcoholics with 100 g of daily intake). This phenotype was expressed as the 6-hydroxy CHZ/CHZ ratio. Results: The rare allele frequency was found to be 1.58% in whites (n= 349). Neither significant association with alcoholism or alcoholic liver diseases, nor relationship with the Pst I/Rsa I polymorphism, was observed. But the Dra I polymorphism was more frequent among the heterozygous subjects when compared with wild-type homozygous ones (p < 0.05). The CYP2E1 phenotype was similar in wild-type homozygotes and in heterozygotes at the constitutive level, as well as after induction with ethanol. Conclusions: Our data suggest that CYP2E1 repeat polymorphism does not seem to constitute a major factor for interindividual differences in CYP2E1 expression and susceptibility to alcohol-related disorders in whites. [source] Endothelin-1 gene polymorphism and hearing impairment in elderly JapaneseTHE LARYNGOSCOPE, Issue 5 2009Yasue Uchida MD Abstract Objectives/Hypothesis: To investigate the association between the Lys198Asn (G/T) polymorphism (rs5370) in the endothelin-1 gene (EDN1) and hearing impairment in middle-aged and elderly Japanese. Study Design: Longitudinal study. Methods: Data were collected from community-dwelling Japanese adults who participated in the Longitudinal Study of Aging biennially between 1997 and 2006. The participants at baseline were 2,231 adults aged 40 years to 79 years. An average hearing threshold level of 25 dB or better in the better ear for frequencies 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz was defined as no hearing impairment. Using generalized estimating equations to treat repeated observations within subjects, 7,097 cumulative data were analyzed to assess the association between hearing status and the EDN1 G/T polymorphism with adjustment for age, sex, histories of ear disease, occupational noise exposure, heart disease, hypertension, and body mass index under additive, dominant, and recessive genetic models. Results: Comparison with wild-type homozygotes (GG), heterozygotes, and mutant homozygotes (GT/TT) showed a positive association with hearing impairment after adjustment for age in model 1 (odds ratio [OR] = 1.24; 95% confidence interval [CI] = 1.02,1.50; P = .033), for age and sex in model 2 (OR = 1.29; CI = 1.06,1.57; P = .0122), and for age, sex, history of ear disease, and history of occupational noise exposure in model 3 (OR = 1.31; CI = 1.07,1.60; P = .0092). The association was also significant in model 3 under the additive model. Conclusions: This study demonstrated that mutant T-allele carriers were associated with a higher risk of hearing impairment than carriers of wild-type homozygotes in middle-aged and elderly people. This result implies that endothelin-1 plays a valuable role in the cochlea. Laryngoscope, 2009 [source] The relation between two polymorphisms in the glucocorticoid receptor gene and body mass index, blood pressure and cholesterol in obese patientsCLINICAL ENDOCRINOLOGY, Issue 1 2003Anna Maria Di Blasio Summary objective ,We have recently reported that, in healthy elderly Dutch individuals, a N363S polymorphism in the glucocorticoid receptor (GR) gene is associated with higher sensitivity to low-dose dexamethasone (0·25 mg), evaluated as both cortisol suppression and insulin response, and with an increased body mass index (BMI). In the present study we investigated the role of the N363S polymorphism, and a BclI restriction site polymorphism in a group of Italian patients with severe obesity. design Two hundred and seventy-nine patients (mean BMI 45·9 ± 0·9 kg/m2) were genotyped using both PCR-restriction fragment length polymorphism analysis and Taqman Sequence Detection System. Determination of several metabolic and antropometric parameters was also performed in order to correlate them to the genotype. results In this group of obese patients, 13 subjects (eight female, five males) were heterozygous for the N363S variant (allelic frequency 2·3%) and had significantly higher BMI (P < 0·04), resting energy expenditure (P < 0·03) and food intake (P < 0·01) when compared to wild-type homozygotes. When the data were analysed according to sex, female heterozygotes for the N363S allele had significantly higher BMI (P = 0·04), resting energy expenditure (P = 0·03) and food intake (P = 0·008) than obese women with the wild-type 363 GR gene. Male carriers of this variant also had higher values for these variables although the differences did not reach statistical significance. A case,control study with homozygous wild-type obese subjects which were age-, sex- and BMI-matched, revealed no difference in resting energy expenditure and food intake. The allele frequency of the BclI variant was 27% (89 females and 41 males out of 269 subjects). No differences in anthropometric and metabolic parameters were found between subjects heterozygous or homozygous for this variant GR in this obese population. However, when we studied the effect of the presence of the BclI polymorphism and the N363S variant in the same individual, we found that the subjects who carried both polymorphisms had a tendency towards higher systolic and diastolic blood pressure and significantly higher total and LDL-cholesterol levels (P = 0·005 and P = 0·05, respectively). discussion Taking the results of this study and those obtained in the Dutch population, we speculate that heterozygous carriers of the N363S variant who develop obesity, may become even more obese, possibly because they have a hypersensitive insulin response and thus, via activation of lipogenesis, store fat more efficiently. Furthermore, these data suggest that N363S carriers who carry the BclI polymorphism as well, tend to have a slightly unfavourable cardiovascular profile. [source] | ||||||||||