Encephalopathy mimicking non-convulsive status Epilepticus.

Primary hyperammonemic encephalopathy due to urea cycle disorders (UCD) typically manifests with episodic unresponsiveness and this clinical entity is not often included in the differential diagnosis of presumed non-convulsive status epilepticus (NCSE). However, this diagnostic consideration has therapeutic implications. In this report, we document the therapeutic importance of elucidating the specific cause of hyperammonemic encephalopathy that closely mimicked NCSE through 2 unique illustrative cases.

Common Variants in the Sex Hormone-Binding Globulin (SHBG) Gene Influence SHBG Levels in Women with Polycystic Ovary Syndrome.

BACKGROUND: Decreased sex hormone-binding globulin (SHBG) levels were associated with polycystic ovary syndrome (PCOS). SHBG polymorphisms associated with reduced SHBG production were tested for their association with PCOS, but with inconclusive results. We tested whether altered SHBG levels and SHBG variants were associated with PCOS. METHODS: The study subjects included 242 women with PCOS and 238 control women. SHBG genotyping was done by real-time PCR. RESULTS: Higher minor allele frequency of rs13894, rs858521 and rs727428 was seen in PCOS cases, and significant differences in rs858521 and rs727428 genotypes distribution were seen between PCOS cases and controls. Multivariate regression analysis confirmed the association of only rs727428 with PCOS. Though it was not statistically significant, serum SHBG levels were reduced according to rs727428 genotypes in PCOS cases than in controls. Carriage of rs727428 minor allele was associated with significant increases in free/bioactive testosterone in PCOS cases. Seven-locus (rs9898876-rs13894-rs858521-rs1799941-rs6257-rs6259-rs727428) haploview analysis showed increased frequency of GCCGTGA, GTCGTGA and GTCATGG, and reduced frequency of GTCGTGG haplotypes in PCOS cases than in controls, thus conferring disease susceptibility and protective nature to these haplotypes, respectively. CONCLUSION: Specific SHBG variants affecting serum SHBG levels and SHBG haplotypes are associated with PCOS, suggesting the role for SHBG as PCOS candidate gene.

Contribution of JAK2 and STAT3 variants to the genetic susceptibility of recurrent miscarriage among Bahraini and Tunisian Arabs.

We investigated the contribution of JAK2 rs2203724 and STAT3 rs1053023 and rs1053004 to the susceptibility of idiopathic recurrent miscarriage (IRM) in Bahraini (246 cases and 279 controls) and Tunisian (235 cases and 235 controls) Arabs. The distribution of JAK2 rs2203724 and STAT3 rs1053023 genotypes were in Hardy-Weinberg equilibrium (HWE) in both communities, while mild deviation from HWE was noted for rs1053004 in Tunisians but not Bahraini. JAK2 rs2203724 was not associated with IRM in either community, while STAT3 rs1053023 was positively associated with IRM in both Bahraini and Tunisian women. STAT3 rs1053004 displayed mixed association: it was positively associated with IRM in Bahraini (P < 0.001), but not Tunisian women (P = 0.10). Genotype association confirmed the association of both STAT3 variants with IRM under additive, dominant, and recessive models, while the association of STAT3 rs1053023 was seen under additive and dominant, but not recessive models in Tunisians. The contribution of JAK2 and STAT3 variants to IRM susceptibility must be evaluated regarding specific variants, and the ethnic/racial background.

Contribution of JAK2 and STAT3 variants to the genetic susceptibility of recurrent spontaneous miscarriage in a Tunisian population.

AIMS: Th1 and Th2 balance is crucial for maintenance of pregnancy, and intracellular JAK and STAT proteins significantly contribute to it. In view of evidence linking JAK2 and STAT3 variants with recurrent spontaneous miscarriage (RSM), here we investigated the association of JAK2 (rs2230724) and STAT3 (rs1053023 and rs1053004) to RSM susceptibility in Tunisians. SUBJECTS AND METHODS: A retrospective case-control study. Subjects comprised 235 RSM cases and 235 control subjects. JAK2 and STAT3 were genotyped by the allelic discrimination method. RESULTS: STAT3 rs1053023 and, to a lower extent, rs1053004 were significantly associated with RSM under the additive and dominant, but not recessive models. This remained significant after adjustment for the covariates age, smoking, and gravida. In contrast to STAT3 variants, JAK2 rs2230724 was not associated with RSM under any of the genetic models tested. Two-locus STAT3 (rs1053023/rs1053004) haplotype analysis revealed increased frequency of the C/G haplotype in patients with RSM. Multivariate regression analysis confirmed the association of C/G haplotype with RSM (p=0.001; odds ratio=2.01; 95% confidence interval=1.32-3.07), thus conferring RSM susceptibility nature. These differences remained significant after applying the Bonferroni correction for multiple testing (Pc=0.004). CONCLUSIONS: STAT3 rs1053023, more so than the STAT3 rs1053004 or JAK2 rs2230724 polymorphisms, is associated with RSM risk.

Lack of association between genetic polymorphisms within KCNQ1 locus and type 2 diabetes in Tunisian Arabs.

AIMS: Polymorphisms of KCNQ1 were previously associated with type 2 diabetes (T2DM) in select Caucasian and non-Caucasian populations. We investigated the association of rs231361, rs231359, rs151290, rs2237892, rs2283228, rs2237895, and rs2237896 KCNQ1 polymorphisms with T2DM in Tunisian Arabs. SUBJECTS AND METHODS: Subjects comprised 900 T2DM patients and 600 normoglycemic controls. KCNQ1 genotyping was done by allelic discrimination (real-time PCR) and PCR-RFLP methods; the contribution of KCNQ1 polymorphisms to T2DM were analyzed by Haploview and regression analysis. RESULTS: Minor allele frequency (MAF) of the 7 tested KCNQ1 variants was comparable between T2DM cases and controls. Mild association of rs2237892 genotypes with T2DM was seen (P=0.014), highlighted by the significant association of the C/T genotype with increased T2DM risk (OR, 2.11; 95%CI, 1.25-3.53), after adjusting for BMI, gender, systolic and diastolic blood pressure, and serum lipid profile. Heterogeneity in linkage disequilibrium pattern between tested KCNQ1 variants analyzed was seen. Two-locus (rs231361 and rs231359) and 5-locus (remaining 5 SNPs) haplotype analysis did not reveal any significant association with any of the haplotypes contained in either block 1 or block 2. CONCLUSION: These results indicate that there was no evidence for an association of KCNQ1 polymorphisms with T2DM in Tunisian Arabs.

Analysis of interleukin-18 promoter polymorphisms and changes in interleukin-18 serum levels underscores the involvement of interleukin-18 in recurrent spontaneous miscarriage.

OBJECTIVE: To evaluate the association of interleukin-18 (IL-18) promoter single-nucleotide polymorphisms rs1946519 (-656C/A), rs187238 (-137G/C), rs360718 (-119A/C), and rs360717 (-105G/A) and changes in IL-18 serum levels with recurrent spontaneous miscarriage (RSM). DESIGN: Case-control study. SETTING: Outpatient obstetrics and gynecology clinics. PATIENT(S): Women with confirmed RSM (n = 282), and 283 age- and ethnically matched controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): IL-18 genotyping was accomplished by allelic discrimination assays; serum IL-18 levels were measured by ELISA. RESULT(S): The minor allele frequencies of rs360717 and rs1946519, but not rs360718 or rs187238, were higher in patients with RSM. Significant differences in the distribution of the rs360717 and rs1946519 genotypes were noted between patients and controls, and both rs360717 and rs1946519 IL-18 single-nucleotide polymorphisms showed significant association with RSM under additive, dominant, and recessive models. Lower serum IL-18 levels were seen between patients and controls and were more pronounced in rs360717 and rs1946519 heterozygous and homozygous genotypes. Four-locus (rs1946519/rs187238/rs360718/rs360717) IL-18 haplotype analysis identified that the AGAA (Pc<.001), CGAA (Pc<.001), and ACAG (Pc=.018) haplotypes were associated with a reduction in IL-18 secretion and with increased RSM risk, after adjustments for body mass index, menarche, and gravida. CONCLUSION(S): These results demonstrated that reduced IL-18 levels and rs360717 and rs1946519 IL-18 variants are significantly associated with RSM.