Essential hypertension (EH) affects approximately 20% of the adult population and has a multifactorial origin. Epidemiological survey of 9 villages in the secluded area of Ogliastra revealed that in the genetic isolate of Talana there is the highest EH prevalence (26%). We performed medical examination on the whole population and identified 98 affected individuals with high diastolic blood pressure (>95 mmHg), which belong to a single 12 generation pedigree. This large family was divided in 12 three generation pedigrees including 185 members and 71 patients. We performed a genome wide linkage analysis on these families using 1000 microsatellites. Recombination maps and allele frequencies were calculated in the same population using 800 people. Statistical analysis , with Simwalk2, allowed the identification of 6 loci on chr 2, 8, 17, 18, 22 (-log(P)>3); all of them but the one on chr22 have been already described in association with EH in several population even with the same most significative markers. Genome wide search was replicated on different family structure with 16k SNPs evenly distributed every 150 Kb. For statistical analysis we used Merlin because LD modelling is a concern with highly dense marker maps. With this approach we were able to confirm and refine all the loci but the one on chr18. We are currently carrying out fine mapping in all the positive loci using high density SNPs. On chr 22 locus we identified a gene involved in cardiovascular development which shows a strong association with EH. Preliminary results of GWA using 90 cases and 90 controls genotyped with 500k SNPs showed several genes linked to EH i.e. NEDD4L,TGFA, ADIPOQ, which have been already associated with EH in other studies. To replicate these results we collected a large cohort of 450 cases and 450 controls from 9 different villages in Ogliastra.Our data indicate that several genetic factors common to worldwide population contribute to EH in Talana.
Essential Hypertension is associated to several worldwide genetic factors in a Sardinian genetic isolate
MP Concas;I Persico;G Biino;M Pirastu;A Angius
2007
Abstract
Essential hypertension (EH) affects approximately 20% of the adult population and has a multifactorial origin. Epidemiological survey of 9 villages in the secluded area of Ogliastra revealed that in the genetic isolate of Talana there is the highest EH prevalence (26%). We performed medical examination on the whole population and identified 98 affected individuals with high diastolic blood pressure (>95 mmHg), which belong to a single 12 generation pedigree. This large family was divided in 12 three generation pedigrees including 185 members and 71 patients. We performed a genome wide linkage analysis on these families using 1000 microsatellites. Recombination maps and allele frequencies were calculated in the same population using 800 people. Statistical analysis , with Simwalk2, allowed the identification of 6 loci on chr 2, 8, 17, 18, 22 (-log(P)>3); all of them but the one on chr22 have been already described in association with EH in several population even with the same most significative markers. Genome wide search was replicated on different family structure with 16k SNPs evenly distributed every 150 Kb. For statistical analysis we used Merlin because LD modelling is a concern with highly dense marker maps. With this approach we were able to confirm and refine all the loci but the one on chr18. We are currently carrying out fine mapping in all the positive loci using high density SNPs. On chr 22 locus we identified a gene involved in cardiovascular development which shows a strong association with EH. Preliminary results of GWA using 90 cases and 90 controls genotyped with 500k SNPs showed several genes linked to EH i.e. NEDD4L,TGFA, ADIPOQ, which have been already associated with EH in other studies. To replicate these results we collected a large cohort of 450 cases and 450 controls from 9 different villages in Ogliastra.Our data indicate that several genetic factors common to worldwide population contribute to EH in Talana.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
