Relation between apolipoprotein E genotype, hepatitis B virus status, and thyroid status in a sample of older persons with Down syndrome.

Dementia of the Alzheimer type (DAT) is common in older persons with Down syndrome (DS). There are three common alleles of the apolipoprotein E (ApoE) gene (Sigma 2, Sigma 3, and Sigma 4) resulting in three different isoforms (E2, E3, and E4) and six different genotypes (2,2; 2,3; 2,4; 3,3; 3,4; and 4,4). Sigma 4 is a risk factor for DAT whereas Sigma 2 appears prophylactic. As hepatitis B virus (HBV) infection and hypothyroidism also are common in DS, we evaluated associations between ApoE type, HBV status, and thyroid status in a sample of older persons with DS (n = 55; mean age, 44.3 +/- 10.8 years) using chi-squared analysis. Participants were classified as E2 (2,2 or 2,3), E3 (3,3), or E4 (3,4 or 4,4); positive for markers of HBV infection in the present or past (i.e., total HBcAb+ and/or HBsAg+ with or without infectivity, defined as HBV+) or negative for markers of HBV infection (defined as HBV-) and, currently receiving thyroid hormone supplement (defined as "hypothyroidism") or having normal thyroid function. The majority of the HBV+ were currently HBcAb+ and HBsAb+, but not HBsAg+. In females, there was an ApoE allele effect on thyroid status (P < or = 0.01), E2 being negatively (P < or = 0.01) and E4 being positively (P < or = 0.05) associated with "hypothyroidism". There was no evidence for an ApoE allele effect on thyroid status in males. There was no evidence for an ApoE allele effect on HBV status, or for an HBV status effect on thyroid status. As thyroid status can affect cognitive function, ApoE allele effects in DAT may, in part, be thyroid effects.

Familial aggregation of diabetes and hypertension in a case-control study of colorectal neoplasia.

Familial aggregation of diseases potentially associated with metabolic syndrome (diabetes mellitus, hypertension, and cardiovascular diseases) was assessed in a colonoscopy-based case-control study of colorectal neoplasia in Toronto and Ottawa, Canada, in 1993-1996. Each familial disease was analyzed by logistic regression using generalized estimating equations. Case probands had incident adenomatous polyps (n = 172) or incident (n = 25) or prevalent (n = 132) colorectal cancer (CRC), while control probands (n = 282) had a negative colonoscopy and no history of CRC or polyps. Significant effect modification was evident in the data, with the strongest positive associations between familial diabetes and colorectal neoplasia among older probands with symptoms (parents: odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.2, 4.8; siblings: OR = 5.8, 95% CI: 2.6, 13.3). Familial hypertension was also associated with colorectal neoplasia among probands with symptoms (OR = 1.7, 95% CI: 1.1, 2.6). In stratified analyses, familial diabetes, hypertension, and stroke were positively associated with adenomatous polyps in subgroups of probands who were older and/or had symptoms, while only familial diabetes was possibly associated with CRC. Associations in other proband groups may have been obscured by high cumulative incidence of parental CRC. Family studies are needed to understand the contribution of specific environmental and genetic factors in accounting for the disease aggregations.