Search

Background and purpose Low density lipoprotein receptor related proteins (LRPs) 1 and 6 have been implicated in cerebral ischaemia. In addition, genetic variation in LRP1 and LRP6 has been linked with various factors that are related to risk of ischaemic stroke. The aim of this study was to examine the association of LRP1 and LRP6 gene variants with risk of ischaemic stroke as part of the Ischemic Stroke Genetics Study ( ISGS). Methods A Caucasian series (434 stroke patients, 319 controls) and an African American series (161 stroke patients, 116 controls) were included. Fourteen LRP6 variants and three LRP1 variants were genotyped and assessed for association with ischaemic stroke. Results In the Caucasian series, significant associations with ischaemic stroke were observed for LRP6 rs2075241 [odds ratio ( OR) 0.42, P = 0.023], rs2302685 ( OR 0.44, P = 0.049), rs7975614 ( OR 0.07, P = 0.017), rs10492120 ( OR 0.62, P = 0.036) and rs10743980 ( OR 0.66, P = 0.037). Risk of ischaemic stroke was significantly lower for carriers of any of these five protective LRP6 variants (24.0% of subjects) compared to non-carriers ( OR 0.57, P = 0.003). The protective association for LRP6 rs2075241 was observed at a similar magnitude across ischaemic stroke subtypes, whilst the effects of rs23022685, rs10492120 and rs10743980 were most apparent for cardioembolic and large vessel stroke. In the African American series, LRP1 rs11172113 was associated with an increased risk of stroke ( OR 1.89, P = 0.006). Conclusions The results of our preliminary study provide evidence that LRP6 and LRP1 variants may be associated with risk of ischaemic stroke. Validation in larger studies is warranted. [ABSTRACT FROM AUTHOR]

Background Ischaemic stroke shares common traditional risk factors with coronary artery disease ( CAD) and myocardial infarction ( MI). This study evaluated whether genetic risk factors for CAD and MI also affect susceptibility to ischaemic stroke in Caucasians and African Americans. Methods Included in the study were a Caucasian series (713 ischaemic stroke patients, 708 controls) and a small African American series (166 ischaemic stroke patients, 117 controls). Twenty single-nucleotide polymorphisms ( SNPs) previously shown to be associated with CAD or MI were genotyped and assessed for association with ischaemic stroke and ischaemic stroke subtypes using odds ratios ( ORs) from multivariable logistic regression models. Results In Caucasians, four SNPs on chromosome 9p21 were significantly associated with risk of cardioembolic stroke, the strongest of which was rs1333040 ( OR 1.55, P = 0.0007); similar but weaker trends were observed for small vessel stroke, with no associations observed regarding large vessel stroke. Chromosome 9p21 SNPs were also associated with risk of ischaemic stroke in African Americans (rs1333040, OR 0.65, P = 0.023; rs1333042, OR 0.55, P = 0.070; rs2383207, OR 0.55, P = 0.070). The PSMA6 SNP rs1048990 on chromosome 14q13 was associated with overall ischaemic stroke in both Caucasians ( OR 0.80, P = 0.036) and African Americans ( OR 0.31, P = 0.020). Conclusions Our results provide evidence that chromosome 9p21 variants are associated with cardioembolic ischaemic stroke in Caucasians and with overall ischaemic stroke in African Americans. The PSMA6 variant rs1048990 also appears to affect susceptibility to ischaemic stroke in both populations. These findings require validation, particularly the preliminary findings regarding African Americans given the small size of that series. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that variation in the SNCA, MAPT, and GSK3B genes interacts in affecting risk for Parkinson disease (PD). In the current study, we attempt to validate previously published findings, evaluating gene-gene interactions between SNCA, MAPT, and GSK3B in association with PD. Three Caucasian PD patient-control series from the United States, Ireland, and Norway (combined n = 1020 patients and 1095 controls) were genotyped for SNCA rs356219, MAPT H1/H2-discriminating SNP rs1052553, and GSK3B rs334558 and rs6438552. Our findings indicate that as previously reported, the SNCA rs356219-G allele and MAPT rs1052553 (H1 haplotype) were both associated with an increased risk of PD, whilst contrary to previous reports, GSK3B variants were not. No pair-wise interaction was observed between SNCA, MAPT, and GSK3B; the risk effects of SNCA rs356219-G and MAPT rs1052553-H1 were seen in a similar manner across genotypes of other variants, with no evidence suggesting synergistic, antagonistic, or deferential effects. In the Caucasian patient-control series examined, risk for PD was influenced by variation in SNCA and MAPT but not GSK3B. Additionally, those three genes did not interact in determining disease risk. [ABSTRACT FROM AUTHOR]

Background The incidence rates of gastric and oesophageal adenocarcinoma are changing significantly, but little is known about specific sub-sites. Aim To use a population-based approach to describe the trends in the site-specific incidence of oesophageal and gastric adenocarcinoma. Methods Using the Rochester Epidemiology Project, all cases of gastric and oesophageal adenocarcinoma among Olmsted County, Minnesota, residents first diagnosed between 1971 and 2000 were identified ( n = 186). Complete in-patient and out-patient records were reviewed and site determined from pathological, surgical, endoscopic and radiological reports. Results Between the decades of 1971–1980 and 1991–2000, the incidence of oesophageal adenocarcinoma increased significantly from 0.4 to 2.5 per 100 000 person-years. The incidence of adenocarcinoma of the oesophagogastric junction also increased from a rate of 0.6 to 2.2 per 100 000 person-years. The incidence rate of cancer involving the gastric cardia was stable but the incidence of adenocarcinoma involving distal gastric sites declined. Combined oesophageal and oesophagogastric junction adenocarcinoma (4.7 per 1 000 000 person-years) was as common as gastric adenocarcinoma (3.4 per 100 000 person-years) in 1991–2000. Conclusions The incidence rates of adenocarcinoma involving proximal gastric sub-sites do not appear to be increasing in a manner similar to those involving oesophageal sub-sites. [ABSTRACT FROM AUTHOR]