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  • 1
    ISSN: 1432-0428
    Keywords: Keywordsβ3-adrenergic-receptor gene ; obesity ; insulin resistance syndrome ; genetics ; polymorphism.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated whether the polymorphism of the β 3-adrenergic receptor (β 3-AR) gene, which is associated with insulin resistance in non-diabetic subjects and an earlier onset of non-insulin-dependent diabetes mellitus in Pima Indians, was associated with visceral fat obesity and features of the insulin resistance syndrome in Japanese premenopausal obese women. There was no difference between 131 obese women and 256 control subjects (0.23 vs 0.17, p = 0.112) in the frequency of the Arg64 allele. The visceral fat area measured by computerised tomography scan was greater in homozygous Arg64Arg (172 ± 17 cm2, n = 6) and heterozygous Trp64Arg (178 ± 47 cm2, n = 48) women than in women homozygous for the Trp64Trp (121 ± 46 cm2, n = 77) genotype (p 〈 0.01). This was also reflected by increased total body fat but not by increased body mass index. The association between the Trp64 allele and visceral fat mass by multiple regression analysis, was independent of age, body mass index and total fat mass (p 〈 0.004). Moreover, homozygous carriers of the Arg64 allele had higher systolic blood pressure, higher fasting and post-load glucose and insulin concentrations, higher cholesterol, and triglyceride and lower HDL-cholesterol concentrations than homozygous carriers of the Trp64 allele. Some of these differences were also observed between heterozygous Trp64Arg and homozygous Trp64Trp genotypes (glucose tolerance, insulin and cholesterol concentration). We conclude that in obese women the β 3-AR polymorphism may be used as a genetic marker for visceral fat obesity and the insulin resistance syndrome. [Diabetologia (1997) 40: 200–204]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-232X
    Keywords: Key words Acute intermittent porphyria (AIP) ; Gene analysis ; Hydroxymethylbilane synthase (HMBS) ; Molecular pathology ; Mutations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Acute intermittent porphyria (AIP) is an autosomal dominant inherited disease caused by a decreased activity of hydroxymethylbilane synthase (HMBS). Regarding the abnormalities of the HMBS gene, many different mutations have been reported worldwide; however, few families from Japan have been studied. In this work, we investigated the presence of mutations in two unrelated Japanese patients with AIP. Mutational analysis was performed using the polymerase chain reaction-single strand conformation polymorphism (SSCP) method, followed by DNA sequencing. Reliable restriction enzyme cleavage assays were also established for the pedigree analyses. Unique SSCP patterns were noted in exons 12 and 15 of the HMBS gene. Sequencing revealed different mutations in each patient: a two-base deletion of CT at nucleotide 730–731 (730delCT), and also a two-base deletion of CA at position 982–983 (982delCA). Both of the deletion mutations lead to truncated proteins with an abnormal C-terminus, which would be expected to decrease the stability and/or activity of HMBS. Using the cleavage assays, we were able to definitively identify gene carriers in the family. This study adds a novel mutation to those that have been previously reported, and emphasizes that molecular analysis would be very useful not only for the identification of asymptomatic gene carriers in the family but also for the detection of ancestral founders in porphyria families.
    Type of Medium: Electronic Resource
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