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  • 1
    ISSN: 1435-232X
    Schlagwort(e): Key words Complex disease ; Carbohydrate ; Insulin ; Aboriginal populations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract We undertook a genome-wide scan using 190 markers with an average separation of 20 cM in 49 Canadian Oji-Cree sib pairs affected with type 2 diabetes. Four of these markers, one each on chromosomes 6, 8, 16, and 22, showed both suggestive linkage and suggestive association with type 2 diabetes in the Oji-Cree. None of these markers corresponded to any chromosomal region or marker that has so far been linked with type 2 diabetes in other populations. Thus, there might be several genetic loci that confer susceptibility to type 2 diabetes in this study sample. We are following up on these preliminary leads by increasing the density of the markers within these linked and associated regions, and also by increasing the number of study subjects. Also, we found instances in which there were wide disparities between the Oji-Cree and reference Caucasians with respect to marker heterozygosity. This suggests that a particular set of markers for genome-wide scanning will have different informativeness in different ethnic groups. Thus, different marker sets will likely be required for different ethnic groups in order to maximize their information content for linkage calculations.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1435-232X
    Schlagwort(e): Key words Atherosclerosis ; Hypertension ; Gene expression ; Linkage disequilibrium ; Small genetic effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract We previously reported significant associations between variation in the AGT gene at codon 235 and both systolic pressure and hypertension in Canadian Oji-Cree. Recently, Inoue et al suggested that the AGT T235 variant was not causative, but was rather in linkage disequilibrium with a variant in the AGT promoter, namely −6A, that was associated with increased in vitro expression of angiotensinogen and was thus a strong candidate to be the functional basis of the previously observed associations. We genotyped 518 adult Oji-Cree for the AGT promoter polymorphism and tested for its association with blood pressure and hypertension. We found that the frequency of the −6A variant was 0.85 in the Oji-Cree, which is much higher than the frequency observed in other human samples. We also found strong linkage disequilibrium between the AGT−6A and T235 variants. However, genetic variation of the AGT promoter was only marginally associated with variation in systolic pressure, with a trend to significantly higher systolic pressure seen in AGT−6A/A homozygotes than in subjects with other genotypes. In addition, genetic variation of the AGT promoter tended to be associated with a diagnosis of hypertension. Despite the very high prevalence of −6A, our native sample was essentially normotensive. Our findings are consistent with a marginally deleterious effect of the AGT−6A allele on blood pressure, but linkage disequilibrium with another causative variant cannot be ruled out in this sample of aboriginal Canadians.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1435-232X
    Schlagwort(e): Key words Complex disease ; Cardiovascular ; Sodium ; Aboriginal populations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract Since adducin modulates cellular sodium retention, its follows that ADD1, which encodes the α-subunit of adducin, is an attractive candidate gene for blood pressure variation. Association studies examining the relationship between polymorphism at ADD1 codon 460 (G460W) and both hypertension and blood pressure, which were performed in a variety of human population samples derived from different genetic backgrounds, have given inconsistent results. We examined the association between the ADD1 G460W polymorphism and variation in blood pressure in a sample of non-diabetic, largely normotensive Canadian Oji-Cree from an isolated community in Northern Ontario. Among 481 Oji-Cree subjects, we measured blood pressure and related clinical phenotypes and determined genotypes of ADD1 G460W. We observed an allele frequency of 0.08 for the ADD1 W460 variant, which is among the lowest so far observed in human populations. We found significant associations between variation in both systolic and diastolic blood pressure and gender, age, body mass index (BMI), and treatment for hypertension. However, we found no association between the ADD1 W460 allele and increased blood pressure, nor did we observe a higher frequency of the W460 allele in a hypertensive subgroup compared with normotensive subjects. While the low sample frequency of ADD1 W460 is consistent with the low sample prevalence of hypertension, the absence of a specific association with both blood pressure and hypertension suggests that the ADD1 W460 variant is not an important determinant of blood pressure among individuals of this genetic background.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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