GWAS in an isolated Sardinian population contribute to elucidate the genetic control of serum Angiotensin Converting Enzyme (ACE) level. (Abstract/Poster in atti di convegno)

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Label
  • GWAS in an isolated Sardinian population contribute to elucidate the genetic control of serum Angiotensin Converting Enzyme (ACE) level. (Abstract/Poster in atti di convegno) (literal)
Anno
  • 2012-01-01T00:00:00+01:00 (literal)
Alternative label
  • I. Persico1, M. P. Concas1, G. B. Maestrale1, L. Portas1, F. Murgia1, M. Cosso2, D. Serra2, M. Pirastu1,2 (2012)
    GWAS in an isolated Sardinian population contribute to elucidate the genetic control of serum Angiotensin Converting Enzyme (ACE) level.
    in 62nd Annual Meeting of The American Society of Human Genetics, November 6-10, 2012 in San Francisco, California., San Francisco, California, 6-10 novemre 2012
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • I. Persico1, M. P. Concas1, G. B. Maestrale1, L. Portas1, F. Murgia1, M. Cosso2, D. Serra2, M. Pirastu1,2 (literal)
Note
  • Poster (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1) Institute of Population Genetics, CNR, Sassari, Italy; 2) SharDNA Life Science, Pula, Italy. (literal)
Titolo
  • GWAS in an isolated Sardinian population contribute to elucidate the genetic control of serum Angiotensin Converting Enzyme (ACE) level. (literal)
Abstract
  • INTRODUCTION: ACE, encoded by DCP1 gene, plays a key role in the Renin Angiotensin System which is involved in the control of fluid electrolyte balance and cardiovascular system. A QTL at DCP1 is the major determinant of serum ACE levels and more recently the AB0 locus was found associated with ACE levels by GWAS in hypertensive patients. However these two loci do not fully explain the variability of the trait suggesting a role of other genetic factors. PURPOSE: We aimed to detect the genetic components which determine the serum ACE levels in healthy individuals through GWAS of a genetically homogeneous population. METHOD. Talana is an isolated village characterized by centuries of isolation and high genetic homogeneity. We phenotyped 517 individuals (>18 yrs), genotyped with 2.5 million SNPs, without diseases and not taking medications that may interfere in ACE levels. The GWAS for discovery was carried out in two steps: 1) log10-transformed ACE levels adjusted for sex and principal components; 2) adding the DCP1 gene as covariate. The best hits were replicated in two villages of the same area (Baunei, N=848; Seulo, N=346), with different genetic structure and almost absent intermarriages with Talana, and in 1000 unrelated individuals from outbreed population, all selected with the same criteria. RESULTS: We confirmed the DCP1 locus on chr 17q23 (rs4311, p = 2.3E-18). We identified several loci with p values < 5.0E-8 spread in 10 Mb region (17q23.2-17q24.2) containing the DCP1. We did not observe linkage disequilibrium between all these loci. In addition we observed suggestive signals on chr 9q34.2, in 180 Kb region spanning AB0-SURF4-ADAMTS13 genes which reached a significant p value adding the DCP1 as covariate in GWAS second stage. We replicated the signals of the entire region 9q34.2 both in the two villages and in the outbreed population and we observed a strong effect of the A, B and O alleles on ACE levels. Finally we replicated some of the chr 17 hits (i.e. rs9895941, p=2.18E-9, MARCH10) in the two villages but not in the outbreed population. CONCLUSION: This study confirms the independent role played by DCP1 and AB0-Surf4-ADAMTS13 loci in the genetic control of the ACE level. It is interesting to note that both loci have been associated with cardiovascular disease. We also highlighted, thanks to the peculiar genetic structure of our isolated population, new genes/loci that should be confirmed with new genetic and functional studies. (literal)
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