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Single nucleotide polymorphisms in the 3′ untranslated and near gene regions of transthyretin may play a role in senile systemic amyloidosis
Author(s) -
Sikora Jacquelyn L,
Spencer Brian H,
Prokaeva Tatiana B,
Connors Lawreen H
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.874.30
Subject(s) - single nucleotide polymorphism , haplotype , genetics , snp , allele , biology , genotype , amyloidosis , untranslated region , transthyretin , linkage disequilibrium , gene , medicine , endocrinology , messenger rna
Senile Systemic Amyloidosis (SSA) is a disease occurring mainly in elderly Caucasian males, estimated to affect approximately 25% of individuals over 80 years of age. SSA usually presents as cardiomyopathy caused by extracellular deposits of amyloid fibrils composed of the plasma protein, transthyretin (TTR). We hypothesized that genetic variation in regulatory regions of the TTR gene may contribute to SSA. We examined SNP variations in a region of ~800 bases spanning the 3′ untranslated and near gene regions of the TTR gene in a group of patients with SSA (n=88). For comparison, a group of controls (n=10) matched for age, gender, and race were analyzed. Of 24 previously reported SNPs in this region, we identified one novel and 3 common SNPs, rs62093482, rs1791228, and rs75032823 in our samples. The odds ratios (OR) calculated under allele analysis for these SNPs were >;1, indicating at least one SNP may be associated with SSA. Genotype analysis revealed OR of 7 and 5 under the recessive model for rs62093482 and rs1791228, respectively, and OR of 3 under the dominant model for rs75032823. Haplotype analysis revealed a haplotype block unique to the SSA group including the three SNPs. The common haplotype identified had an OR of 2.5, indicative of association with SSA, and included alleles with high OR for each SNP. This research is supported by the Gruss Foundation, Boston University Amyloid Fund, the Young Family Amyloid Research Fund, and NIH grant RO1AG031804 (LHC).