RESUMO
BACKGROUND: Abdominal aortic aneurysm (AAA) is a complex disorder in which environmental and genetic factors play a role in pathogenesis. Linkage to 2 adjacent loci on 19q13 in familiar AAA was previously demonstrated. We studied whether genetic variation within these regions predisposes to AAA. METHODS: Common genetic variants in the described regions on 19q13 were analyzed using tag single nucleotide polymorphisms (SNPs) in a Dutch case-control population. Single nucleotide polymorphism genotyping was performed in a 2-stage approach. RESULTS: In stage 1, 615 SNPs were genotyped in 376 AAA patients and 648 controls. In stage 2, 8 SNPs of stage 1 with a P value < .015 were genotyped in a second independent cohort of 360 cases and 376 controls. No differences in allele frequencies were observed. CONCLUSION: Our findings suggest that there are no common AAA predisposing SNPs within the 19q13 loci. Hence, the genetic basis of familiar and sporadic AAA may differ.
Assuntos
Aneurisma da Aorta Abdominal/genética , Cromossomos Humanos Par 19 , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Feminino , Frequência do Gene , Estudos de Associação Genética , Ligação Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: A genetic variant on chromosome 9p21 associates with abdominal aortic aneurysm (AAA) and intracranial aneurysm (IA), indicating that despite the differences in pathology there are shared genetic risk factors. We investigated whether the IA susceptibility genes heparan sulfate proteoglycan 2 (HSPG2) and chondroitin sulfate proteoglycan 2 (CSPG2) associate with AAA as well. METHODS: Using tag single nucleotide polymorphisms (SNPs), all common variants were analyzed in a Dutch AAA case-control population in a 2-stage genotyping approach. In stage 1, 12 tag SNPs in HSPG2 and 22 tag SNPs in CSPG2 were genotyped in 376 patients and 648 controls. Genotyping of significantly associated SNPs was replicated in a second independent cohort of 360 cases and 376 controls. RESULTS: In stage 1, no HSPG2 SNPs and 1 CSPG2 SNP associated with AAA (rs2652106, P = .019). Association of this SNP was not replicated (P = .342). CONCLUSIONS: Our findings demonstrate that, in contrast to IA, HSPG2 and CSPG2 do not associate with AAA.
