OBJECTIVE: Pre-eclampsia is the result of impaired trophoblast invasion and spiral artery remodeling managed by inflammatory response in its etiology and physiopathology. The aim of this study was to compare serum molecules including IL-33, ADAMTS12, ADAMTS16 and ADAMTS18
S18 levels between pre-eclampsia and control groups and to investigate the role of these molecules in pre-eclampsia. METHODS: Forty-one women diagnosed as pre-eclampsia between 30 and 40 weeks of gestation and 41 non-complicated pregnant women were enrolled in this cross-sectional, case-control prospective study. ELISA method was used to determine IL-33, ADAMTS12, ADAMTS16 and ADAMTS18 levels within serums in two groups. RESULTS: Serum ADAMTS12 and IL-33 levels were significantly lower in pre-eclampsia group (p < 0.001 and p: 0.028, respectively), however, in sub-group analysis, no significant difference was observed (p > 0.05). The cut-off value of ADAMTS12 levels to discriminate pre-eclampsia with %73.17 sensitivity and %92.68 specificity was 8.27 ng/ml while the cut-off value for IL-33 was 0.23 pg/ml with 82.93% sensitivity and 53.66% specificity. CONCLUSION: Pre-eclampsia is associated with lower serum IL-33 and ADAMTS12 levels.
Xu B, etal., Int J Mol Sci. 2015 Jan 5;16(1):1051-65. doi: 10.3390/ijms16011051.
To identify tumor suppressor genes (TSGs) silenced by hypermethylation and discover new epigenetic biomarkers for early cancer detection. ADAMTS18, located at 16q23.1, has been reported to be a critical TSG in multiple primary tumors; however, this has not yet
been verified in clear cell renal cell carcinoma (ccRCC). We explored epigenetic alterations in this gene in ccRCC and analyzed possible clinicopathological associations. We examined ADAMTS18 gene expression and methylation by semi-quantitative reverse transcription PCR (RT-PCR) and methylation-specific polymerase chain reaction (MSP) in 5 ccRCC-derived cell lines before and after treatment with 5-aza-2'-deoxycytidine (5-AzaC). MSP was further performed for 101 ccRCC primary tumors and 20 adjacent normal tissues. Some cell lines and specimens were examined by subsequent bisulfite genomic sequencing (BGS) and real-time PCR. Further, we analyzed the relationship between the ADAMTS18 gene methylation and clinicopathological features, including short-term disease-free survival (DFS), in patients with ccRCC. ADAMTS18 down-regulation and hypermethylation were detected in the ccRCC-derived cell lines using RT-PCR and MSP. Treatment with 5-AzaC reversed the hypermethylation of the ADAMTS18 gene and restored its expression. Hypermethylation was further detected in 44 of 101 (43.6%) primary tumors and 3 of 20 (15.0%) adjacent normal tissues. However, a significant difference between both groups was observed (p = 0.02). BGS analysis and real-time PCR were subsequently performed to confirm the results of RT-PCR and MSP. Furthermore, the methylation status of ADAMTS18 was not significantly associated with gender, age, location, tumor diameter, pathological stage, nuclear grade or short-term DFS in patients with ccRCC (p > 0.05). The ADAMTS18 gene is often down-regulated by hypermethylation in ccRCC-derived cell lines and primary tumors, indicating its critical role as a TSG in ccRCC. We conclude that ADAMTS18 gene hypermethylation may be involved in the tumorigenesis of ccRCC and may serve as a novel biomarker for this disease.
One of us recently described an apparently novel ocular syndrome characterized by microcornea, myopic chorioretinal atrophy, and telecanthus (MMCAT) in a number of Saudi families. Consistent with the presumed pseudodominant inheritance in one of the original families, we show that MMCAT maps to a si
ngle autozygous locus on chr16q23.1 in which exome sequencing revealed a homozygous missense change in ADAMTS18. Direct sequencing of this gene in four additional probands with the same phenotype revealed three additional homozygous changes in ADAMTS18 including two nonsense mutations. Reassuringly, the autozygomes of all probands overlap on the same chr16q23.1 locus, further supporting the positional mapping of MMCAT to ADAMTS18. ADAMTS18 encodes a member of a family of metalloproteinases that are known for their role in extracellular matrix remodeling, and previous work has shown a strong expression of Adamts18 in the developing eye. Our data suggest that ADAMTS18 plays an essential role in early eye development and that mutations therein cause a distinct eye phenotype that is mainly characterized by microcornea and myopia.
