Citations

Background Higher mortality for patients with aneurysmal subarachnoid haemorrhage has been reported. Aims In families with intracranial aneurysms, we sought to determine whether mortality among subjects with intracranial aneurysm (affected) was higher and related to rupture, compared with unaffected family members. Methods Subjects enrolled in the Familial Intracranial Aneurysm protocol were contacted yearly and their status was obtained. If reported to be deceased, the cause of death was verified by available records. A Cox proportional hazards model was utilized to compare mortality rates. Results Of the 2794 subjects, 1073 were affected and 1721 were unaffected. There were 8525 person-years of follow-up (mean 3·05 ± 1·73 years) and 85 deaths. Age at study entry for the affected (58·4 ±11·9 years) was significantly older ( P < 0·0001) than for the unaffected (52·2 ± 16·1). After adjusting for age, the overall mortality rate for the affected subjects was not significantly different from that for the unaffected (Rate Ratio [RR] 1·26, 95% confidence interval 0·82–1·93, P = 0·292). There was a strong effect modification due to age. The mortality rate ratio of the affected to the unaffected who were ≤60 years of age was RR = 3·48 (95% confidence interval: 1·59–7·63, P = 0·002), the rate for the affected subjects who were ≥60 was less than the rate for the unaffected (RR = 0·69, 95% confidence interval: 0·404–1·19, P = 0·178). The affected who had ruptures had 2·62 times the mortality rate as those without ruptures (95% confidence interval 1·43–4·80, P = 0·002). Conclusion The overall mortality was similar for the affected and unaffected subjects in this cohort. Among the affected only, those with ruptured intracranial aneurysm had a higher mortality rate than those without ruptured.

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is a precursor to multiple myeloma and related diseases. The majority of MGUS cases are characterized by the expression of immunoglobulin heavy chain (IgH); however, approximately one-fifth of MGUS cases do not present with IgH expression. These individuals have light chain MGUS (LC-MGUS), a precursor to light-chain MM (LC-MM). LC-MGUS is characterized by an absence of IgH and an abnormal free light chain ratio (FLC-R), indicating excessive expression of either κ or ≤ free light chains. LC-MGUS has a prevalence of 0.8% in the general population over the age of 50, as compared with a prevalence of 3.2% for heavy-chain MGUS (HC-MGUS) (Dispenzieri, 2010). There is currently little understanding of the association between family history of HC-MGUS or multiple myeloma (MM) and LC-MGUS. We investigated whether the prevalence of LC-MGUS is elevated in first-degree relatives of patients with either HC-MGUS or MM. HC-MGUS probands expressed IgH and were recruited through a population-based study of Olmsted County residents; MM probands consisted of both HC-MM and LC-MM and were recruited through the Mayo Clinic Hematology practice. Serum samples were collected from first-degree relatives of probands older than 40 years of age and subjected to electrophoresis, immunofixation, and free light chain assay. Prevalence of LC-MGUS was calculated in all first-degree relatives combined, and in relatives from both HC-MGUS and MM families separately. We compared the prevalence in family members to that in a well-defined Olmsted County, MN cohort (Dispenzieri, 2010) of patients aged 50 and over. A total 911 relatives of 232 MM and 97 MGUS patients were studied. LC-MGUS was detected in 17/911 (1.9%) relatives, for an age- and sex-adjusted prevalence of 1.7% (95% CI, 0.9% to 2.6%). Prevalence among relatives of MM probands (age- and sex- adjusted rate 2.1%; 95% CI, 1.0% to 3.2%) was higher than among relatives of MGUS probands (age- and sex- adjusted rate 0.6%; 95% CI, 0.0%-1.6%). There was an increased risk of LC-MGUS in relatives compared to the reference population which was predominantly due to the increased risk among relatives of MM probands (risk ratio=3.4, 95% CI 2.0, 5.51) as opposed to relatives of MGUS probands (risk ratio=1.1, 95% CI, 0.3 to 4.5). Among MM probands, there was no significant difference between the prevalence increase in relatives of the 32 probands with LC-MM and that of the relatives of the 200 probands with HC-MM (3.8 vs 3.3, ratio=1.2, 95% CI: 0.3-5.1, p=0.85). We conclude that the prevalence of LC-MGUS is significantly higher among first degree family members of all MM probands compared to the general population. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5485. doi:1538-7445.AM2012-5485

AbstractTo further explore reports of association of alcohol dependence and response to acamprosate treatment with the GATA4 rs13273672 single nucleotide polymorphism (SNP), we genotyped this and 10 other GATA4 SNPs in 816 alcohol‐dependent cases and 1248 controls. We tested for association of alcohol dependence with the 11 SNPs individually and performed a global test for association using a principle components analysis. Our analyses demonstrate significant association between GATA4 and alcohol dependence at the gene level (P = 0.009) but no association with rs13273672. Further studies are needed to identify potential causal GATA4 variation(s) and the functional mechanism(s) contributing to this association.