Dataset Information

Familial aggregation of albuminuria and arterial hypertension in an Aboriginal Australian community and the contribution of variants in ACE and TP53.

ABSTRACT:

Background

Aboriginal Australians are at high risk of cardiovascular, metabolic and renal diseases, resulting in a marked reduction in life expectancy when compared to the rest of the Australian population. This is partly due to recognized environmental and lifestyle risk factors, but a contribution of genetic susceptibility is also likely.

Methods

Using results from a comprehensive survey of one community (N = 1350 examined individuals), we have tested for familial aggregation of plasma glucose, arterial blood pressure, albuminuria (measured as urinary albumin to creatinine ratio, UACR) and estimated glomerular filtration rate (eGFR), and quantified the contribution of variation at four candidate genes (ACE; TP53; ENOS3; MTHFR).

Results

In the subsample of 357 individuals with complete genotype and phenotype data we showed that both UACR (h² = 64%) and blood pressure (sBP h² = 29%, dBP, h² = 11%) were significantly heritable. The ACE insertion-deletion (P = 0.0009) and TP53 codon72 polymorphisms (P = 0.003) together contributed approximately 15% of the total heritability of UACR, with an effect of ACE genotype on BP also clearly evident.

Conclusions

While the effects of the ACE insertion-deletion on risk of renal disease (especially in the setting of diabetes) are well recognized, this is only the second study to implicate p53 genotype as a risk factor for albuminuria - the other being an earlier study we performed in a different Aboriginal community (McDonald et al., J Am Soc Nephrol 13: 677-83, 2002). We conclude that there are significant genetic contributions to the high prevalence of chronic diseases observed in this population.

SUBMITTER: Duffy DL

PROVIDER: S-EPMC5117595 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Publications

Familial aggregation of albuminuria and arterial hypertension in an Aboriginal Australian community and the contribution of variants in ACE and TP53.

Duffy David L DL McDonald Stephen P SP Hayhurst Beverley B Panagiotopoulos Sianna S Smith Trudy J TJ Wang Xing L XL Wilcken David E DE Duarte Natalia L NL Mathews John J Hoy Wendy E WE

BMC nephrology 20161121 1

<h4>Background</h4>Aboriginal Australians are at high risk of cardiovascular, metabolic and renal diseases, resulting in a marked reduction in life expectancy when compared to the rest of the Australian population. This is partly due to recognized environmental and lifestyle risk factors, but a contribution of genetic susceptibility is also likely.<h4>Methods</h4>Using results from a comprehensive survey of one community (N = 1350 examined individuals), we have tested for familial aggregation of ...[more]

PMID: 27871254

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Project description:ObjectivesThis research examined the familial aggregation of migraine, depression, and their co-occurrence.MethodsDiagnoses of migraine and depression were determined in a sample of 5,319 Australian twins. Migraine was diagnosed by either self-report, the ID migraine™ Screener, or International Headache Society (IHS) criteria. Depression was defined by fulfilling either major depressive disorder (MDD) or minor depressive disorder (MiDD) based on the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. The relative risks (RR) for migraine and depression were estimated in co-twins of twin probands reporting migraine or depression to evaluate their familial aggregation and co-occurrence.ResultsAn increased RR of both migraine and depression in co-twins of probands with the same trait was observed, with significantly higher estimates within monozygotic (MZ) twin pairs compared to dizygotic (DZ) twin pairs. For cross-trait analysis, the RR for migraine in co-twins of probands reporting depression was 1.36 (95% CI: 1.24-1.48) in MZ pairs and 1.04 (95% CI: 0.95-1.14) in DZ pairs; and the RR for depression in co-twins of probands reporting migraine was 1.26 (95% CI: 1.14-1.38) in MZ pairs and 1.02 (95% CI: 0.94-1.11) in DZ pairs. The RR for strict IHS migraine in co-twins of probands reporting MDD was 2.23 (95% CI: 1.81-2.75) in MZ pairs and 1.55 (95% CI: 1.34-1.79) in DZ pairs; and the RR for MDD in co-twins of probands reporting IHS migraine was 1.35 (95% CI: 1.13-1.62) in MZ pairs and 1.06 (95% CI: 0.93-1.22) in DZ pairs.ConclusionsWe observed significant evidence for a genetic contribution to familial aggregation of migraine and depression. Our findings suggest a bi-directional association between migraine and depression, with an increased risk for depression in relatives of probands reporting migraine, and vice versa. However, the observed risk for migraine in relatives of probands reporting depression was considerably higher than the reverse. These results add further support to previous studies suggesting that patients with comorbid migraine and depression are genetically more similar to patients with only depression than patients with only migraine.

Dataset Information

Familial aggregation of albuminuria and arterial hypertension in an Aboriginal Australian community and the contribution of variants in ACE and TP53.

Background

Methods

Results

Conclusions

Publications

Familial aggregation of albuminuria and arterial hypertension in an Aboriginal Australian community and the contribution of variants in ACE and TP53.

Similar Datasets

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