RESUMO
<p><b>BACKGROUND</b>In an earlier study, we identified a locus for Moyamoya disease (MMD) on 17q25.3.</p><p><b>METHODS</b>Linkage analysis and fine mapping were conducted for two new families in additional to the previously studied 15 families. Three genes, CARD14, Raptor, and AATK, were selected based on key words, namely, "inflammation", "apoptosis", "proliferation", and "vascular system", for further sequencing. A segregation analysis of 34 pedigrees was performed, followed by a case-control study in Japanese (90 cases vs. 384 controls), Korean (41 cases vs. 223 controls), Chinese (23 cases and 100 controls), and Caucasian (25 cases and 164 controls) populations.</p><p><b>RESULTS</b>Linkage analysis increased the LOD score from 8.07 to 9.67 on 17q25.3. Fine mapping narrowed the linkage signal to a 2.1-Mb region. Sequencing revealed that only one newly identified polymorphism, ss161110142, which was located at position -1480 from the transcription site of the Raptor gene, was common to all four unrelated sequenced familial affected individuals. ss161110142 was then shown to segregate in the 34 pedigrees studied, resulting in a two-point LOD score of 14.2 (P = 3.89 × 10(-8)). Its penetrance was estimated to be 74.0%. Among the Asian populations tested (Japanese, Korean, and Chinese), the rare allele was much more frequent in cases (26, 33, and 4%, respectively) than in controls (1, 1, and 0%, respectively) and was associated with an increased odds ratio of 52.2 (95% confidence interval 27.2-100.2) (P = 2.5 × 10(-49)). This allele was, however, not detected in the Caucasian samples. Its population attributable risk was estimated to be 49% in the Japanese population, 66% in the Korean population, and 9% in the Chinese population.</p><p><b>CONCLUSION</b>ss161110142 may confer susceptibility to MMD among East Asian populations.</p><p><b>ELECTRONIC SUPPLEMENTARY MATERIAL</b>The online version of this article (doi:10.1007/s12199-009-0116-7) contains supplementary material, which is available to authorized users.</p>
RESUMO
Objective To observe the effect of iodine deficiency and hypothyroidism on the protein expressions of calcineurin in the hip-pocampus of pups. Methods Female Wistar rats (n=28) after pregenancy were randomly divided into control group,hypothyroid group and iodine deficient group. According to the dose of propylthiouracil (PTU) in the fed water, hypothyroid group was divided into 5 ppm group and 15 ppm group (7 rats in each group). Totally 5 pups from each group were sacrificed and perfused intracardially in postnatal day (PN) 7,PN14 and PN21. Brains were removed,fixed and sectioned coronally. All sections were observed and analysed for the protein exression of calcineurin by immunohistochemistry in the hippocampus CA1,CA3 and DG regions. Results In PN14 and PN21,protein levels of cal-cineurin in GA1 and CA3 regions of the hippocampus in iodine-deficient and 15 ppm treatment groups were significantly higher than those of the controls (P< 0.05) and in DG region,the contrary was true. In PN7,the positive products were scarely observated in each region and the protein expression was no significantly different in all four groups. Conclusion Iodine deficiency and hypothyroidism may increase the protein expression of calcineurin.