Key result
Carriers of the minor allele (A) of rs11672433 in the ANGPTL4 gene had an increased risk of brain arteriovenous malformations compared to noncarriers.
Why the study?
Are ANGPTL4 gene polymorphisms associated with the risk of brain arteriovenous malformations or intracranial hemorrhage?
Case-Control (n=462)
Are ANGPTL4 gene polymorphisms associated with the risk of brain arteriovenous malformations or intracranial hemorrhage?
A synonymous SNP in ANGPTL4 (rs11672433) is associated with an increased risk of brain arteriovenous malformations, but not with intracranial hemorrhage presentation.
Answers are grounded in this paper and cite their sources.
ANGPTL4 rs11672433 association with brain AVMs should not change practice; hypothesis-generating and requires validation in larger cohorts.
BACKGROUND: Brain arteriovenous malformations (BAVM) are high-flow vascular lesions prone to intracranial hemorrhage (ICH). Abnormal angiogenesis is a key characteristic of BAVM tissue. Angiopoietin-like 4 (ANGPTL4), a secreted glycoprotein, is thought to be involved in angiogenesis and required for proper postnatal blood vessel partitioning. We investigated whether common single nucleotide polymorphisms (SNPs) in ANGPTL4 were associated with risk of BAVM or ICH. METHODS AND RESULTS: We conducted a case-control study of 216 Caucasian BAVM cases and 246 healthy controls, and a secondary case-only analysis, comparing 83 ruptured (ICH) with 133 unruptured BAVM cases at presentation. Four tagSNPs in ANGPTL4 captured variation over a 10-kb region (rs2278236, rs1044250, rs11672433, and rs1808536) and were tested for association with BAVM or ICH. The minor allele (A) of rs11672433 (exon 6, Pro389Pro) was associated with an increased risk of BAVM (p = 0.006), which persisted after adjusting for multiple comparisons (p = 0.03). After adjustments for age and sex, carriers of the minor allele (A) remained at higher risk for BAVM compared to noncarriers (odds ratio, OR = 1.56; 95% confidence interval, CI = 1.01-2.41; p = 0.046) and risk of BAVM was increased with increasing copy of the minor A allele (OR = 1.49, 95% CI = 1.03-2.15; p(trend) = 0.03). Five common haplotypes (frequency >1%) were inferred; overall haplotype distribution differed between BAVM cases and controls (χ(2) = 12.2, d.f. = 4, p = 0.02). Neither SNPs (p > 0.05) nor haplotype distribution (χ(2) = 1.1, d.f. = 4, p = 0.89) were associated with risk of ICH among BAVM cases. CONCLUSION: A synonymous SNP in ANGPTL4 and haplotypes carrying it are associated with risk of BAVM but not with ICH presentation in BAVM cases.
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Mikhak et al. (2011) conducted a case-control in Brain arteriovenous malformations (n=462). ANGPTL4 gene polymorphisms (rs11672433 minor allele A) vs. Noncarriers was evaluated on Risk of BAVM (OR 1.56, 95% CI 1.01-2.41, p=0.046). Carriers of the minor allele (A) of rs11672433 in the ANGPTL4 gene had an increased risk of brain arteriovenous malformations compared to noncarriers.
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