Maternal angiotensinogen (AGT) haplotypes, fetal renin (REN) haplotypes and risk of preeclampsia; estimation of gene-gene interaction from family-triad data.

BACKGROUND: Preeclampsia is a debilitating disorder affecting approximately 3% of pregnant women in the Western world. Although inconclusive, current evidence suggests that the renin-angiotensin system may be involved in hypertension. Therefore, our objective was to determine whether the genes for placental renin (REN) and maternal angiotensinogen (AGT) interact to influence the risk of preeclampsia. METHODS: Three haplotype-tagging SNPs (htSNPs) covering REN (rs5705, rs1464818, and rs3795575) and another three covering AGT (rs2148582, rs2478545 and rs943580) were genotyped in 99 mother-father-child triads of preeclampsia pregnancies. We estimated relative risks (RR) conferred by maternal AGT and fetal REN haplotypes using HAPLIN, a statistical software designed to detect multi-marker transmission distortion among triads. To assess a combined effect of maternal AGT and fetal REN haplotypes, the preeclamptic triads were first stratified by presence/absence of maternal AGT haplotype C-T-A and tested for an effect of fetal REN across these strata. RESULTS: We found evidence that mothers carrying the most frequent AGT haplotype, C-T-A, had a reduced risk of preeclampsia (RR of 0.4, 95% CI = 0.2-0.8 for heterozygotes and 0.6, 95% CI = 0.2-1.5 for homozygotes). Mothers homozygous for AGT haplotypes t-c-g and C-c-g appeared to have a higher risk, but only the former was statistically significant. We found only weak evidence of an overall effect of fetal REN haplotypes and no support for our hypothesis that an effect of REN depended on whether the mother carried the C-T-A haplotype of AGT (p = 0.33). CONCLUSION: Our findings indicate that the mother's AGT haplotypes affect her risk for developing preeclampsia. However, this risk is not influenced by fetal REN haplotypes.

Fatigue in primary Sjögren's syndrome--a link to sickness behaviour in animals?

Interleukin-1beta (IL-1beta) is involved in the regulation of sickness behaviour in response to infection and inflammation in animals. Human fatigue can be considered an element of sickness behaviour and is a prominent and often disabling phenomenon in autoimmune diseases such as primary Sjögren's syndrome (PSS). The role of the IL-1 system in the fatigue of patients with PSS was explored. A cerebrospinal fluid (CSF) analysis of IL-1beta, IL-1Ra, and IL-1sRII was performed in 54 PSS patients and 53 control subjects. Fatigue was evaluated in the patients using the Fatigue Severity Scale (FSS) and a fatigue visual analogue scale (VAS); mood was evaluated using the Beck Depression Inventory (BDI). There were higher CSF levels of IL-1Ra pg/mL in PSS patients vs. controls (median 38.4: range 15.4-81.7 vs. 33.7: 7.3-163.1, p=0.026). Fatigue VAS scores were associated with increasing CSF levels of IL-1Ra in PSS patients (R(2)=0.11, p=0.015). In a subgroup analysis of the non-depressed PSS patients (N=37; 69%), the association between VAS scores and IL-1Ra was even stronger (R(2)=0.20, p=0.006). The positive association between VAS scores and IL-1Ra remained significant in a multiple regression analysis adjusting for age and BDI scores. Increased levels of IL-1Ra in the CSF are associated with increasing fatigue in PSS patients, indicating that the activated IL-1 system is a possible biological factor associated with fatigue.

Chronic myelogenous leukemia with the e6a2 BCR-ABL and lacking imatinib response: presentation of two cases.

The BCR-ABL fusion gene represents the hallmark of chronic myelogenous leukemia (CML) and is derived from a translocation between chromosome 9 and 22. The majority of CML patients have a breakpoint in the major BCR region of the BCR gene giving rise to e13a2 or e14a2 BCR-ABL transcripts. Occasionally, other BCR breakpoints occur. The current report describes two e6a2 CML patients with imatinib treatment failure and unusual disease progression. One patient was Philadelphia chromosome positive and one was Philadelphia chromosome negative with an atypical BCR-ABL rearrangement, ins (22;9).

Hippocampal and ventricular changes in Parkinson's disease mild cognitive impairment.

We analyzed T1-weighted brain magnetic resonance imaging data of 100 cognitively normal elderly controls (NC), 127 cognitively normal Parkinson's disease (PD; PDCN) and 31 PD-associated mild cognitive impairment (PDMCI) subjects from the Norwegian ParkWest study. Using automated segmentation methods, followed by the radial distance technique and multiple linear regression we studied the effect of clinical diagnosis on hippocampal and ventricular radial distance while adjusting for age, education, and scanning site. PDCN subjects had significantly smaller bilateral hippocampal radial distance relative to NC. Nonamnestic PDMCI subjects showed smaller right hippocampal radial distance relative to NC. PDMCI subjects showed significant enlargement of all portions of the lateral ventricles relative to NC and significantly larger bilateral temporal and occipital and left frontal lateral ventricular expansion relative to PDCN subjects. Nonamnestic PDMCI subjects showed significant ventricular enlargement spanning all parts of the lateral ventricle while those with amnestic PDMCI showed changes localized to the left occipital horn. Hippocampal atrophy and lateral ventricular enlargement show promise as structural biomarkers for PD.