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Localization of a gene for peripheral arterial occlusive disease to chromosome 1p31
Gudmundur Gudmundsson1, Stefan E Matthiasson, Haukur Arason
1deCODE Genetics, Reykjavik, Iceland.
Insights
Researchers identified a specific gene locus, PAOD1 on chromosome 1p31, linked to peripheral arterial occlusive disease (PAOD). This finding suggests distinct genetic factors may contribute to vascular disease subtypes.
Area of Science:
- Genetics
- Cardiovascular Disease
- Epidemiology
Background:
- Peripheral arterial occlusive disease (PAOD) stems from atherosclerosis in major arteries, sharing risk factors like smoking, diabetes, hypertension, and hyperlipidemia with coronary and cerebrovascular diseases.
- PAOD often presents concurrently with other cardiovascular and cerebrovascular conditions, indicating potential shared underlying mechanisms.
Purpose of the Study:
- To investigate the genetic underpinnings of peripheral arterial occlusive disease (PAOD) within the Icelandic population.
- To identify potential genetic loci associated with PAOD through a genomewide scan.
Main Methods:
- A population-based cohort of 272 Icelandic PAOD patients, identified through angiography/revascularization records, was cross-matched with a national genealogy database.
- A genomewide scan utilizing microsatellite markers was performed on 116 extended families.
- Linkage analysis was conducted, including an analysis excluding patients with a history of stroke to refine locus identification.
Main Results:
- Significant linkage to chromosome 1p31 was detected, designated as PAOD1, with an allele-sharing LOD score of 3.93.
- Excluding patients with a history of stroke strengthened the linkage, increasing the LOD score to 4.93.
- The results indicate a specific genetic locus associated with PAOD.
Conclusions:
- A novel genetic locus, PAOD1 on chromosome 1p31, is significantly associated with peripheral arterial occlusive disease.
- The findings suggest the existence of genetic factors specific to PAOD, distinct from those contributing to other vascular diseases like stroke, despite shared risk factors.
Abstract:
Peripheral arterial occlusive disease (PAOD) results from atherosclerosis of large and medium peripheral arteries, as well as the aorta, and has many risk factors, including smoking, diabetes, hypertension, and hyperlipidemia. PAOD often coexists with coronary artery disease and cerebrovascular disease. Cross-matching a population-based list of Icelandic patients with PAOD who had undergone angiography and/or revascularization procedures with a genealogy database of the entire Icelandic nation defined 116 extended families containing 272 patients. A genomewide scan with microsatellite markers revealed significant linkage to chromosome 1p31 with an allele-sharing LOD score of 3.93 (P=1.04 x 10(-5)). We designate this locus as "PAOD1." Subtracting 35 patients with a history of stroke increased the LOD score to 4.93. This suggests that, although PAOD and other vascular diseases share risk factors, genetic factors specific to subtypes of vascular disease may exist.