Apoe Calhm1 Gene Polymorphism Is Associated With Temporal Lobe Epilepsy Study The Impact Of The Chinese Version Of Childhood Epilepsy Scale Reliability And Validity

Background and ObjectivesEpilepsy is the second common neurological disorder after cerebrovascular disease. It is estimated that the condition affects approximately 50 million people in the world,80%of whom live in developing countries. Epilepsy brings huge disease burden to the patient, his or her family and the whole society. Mesial temporal lobe epilepsy (MTLE) possesses the highest incidence of adult partial epilepsy and also is the most common drug-resistant epilepsy syndrome. Sporadic MTLE is accepted as a complex disorder attributed to the interaction of genetic and environmental factors. The genetic background plays an important role in induction and maintainance of MTLE. The difference of genetic background in sporadic MTLE population mainly appears as single nucleotide polymorphisms (SNPs). Considerable research has indicated that genetic polymorphism plays a vital role in the susceptibility to MTLE. Some studies indicate that apolipoprotein E (ApoE) may be a susceptibility gene to MTLE. Previous studies indicate that ApoE s4 is associated with several disease-related traits including the increased risk of late posttraumatic seizures, earlier onset of MTLE, refractory complex partial seizures, and postictal confusion. Contradictory data were also reported regarding the association between ApoE polymorphisms and MTLE. The above findings are inconsistent. Furthermore, the genetic background is often different in different geographic area and different ethnicity. Therefore, this study was designed to investigate ApoE gene polymorphisms among the Chinese Han patients with MTLE and its relationship with the clinical variables associated with MTLE. In addition, a recent study identified a SNP (Pro86Leu, rs2986017) in calcium homeostasis regulator 1 (CALHM1) gene influences Ca2+homeostasis and increases cerebral amyloid-β(Aβ) peptide production. Ca2+ homeostasis and high levels of AP in brain are intimately related to MTLE. Thus, we speculate that CALHM1 may be a susceptibility gene, and we also examine the association between CALHM1 gene polymorphisms and MTLE.MethodsThis study, a case-control association study design, was to investigate the association between ApoE and-491A/T polymorphisms and MTLE as well as the clinical variables associated with MTLE in 558 controls and 735 patients including 560 MTLE patients. We also examined the association between CALHM1 gene polymorphisms and MTLE in 401 controls and 560 MTLE patients. We genotyped the polymorphisms by polymerase chain reaction-primer introduced restriction analysis (PCR-PIRA) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In addition, genotyping was performed blindly and 10% of the samples were randomly selected for repeated assays.Results1. Association of ApoE gene polymorphisms with MTLE We detected significant association between prior severe trauma and the ApoEε4 allele in Han Chinese MTLE patients, and the relative risk of MTLE for patients with prior trauma carryingε4 allele was 1.873 (Odds Ratio,1.873; 95%Confidence Interval, 1.084-3.237;p=0.023). There were no statistically significant differences in frequency of ApoE and-491A/T alleles, genotypes or haplotypes between MTLE and control groups. The ApoE s4 allele was not associated with the increased risk of onset of refractory MTLE, refractory complex partial seizures, and postictal confusion.2. Association of SNPs in CALHM1 gene with MTLEA significant allelic association for rs1119692 was observed (OR=1.35,95%CI 1.10-1.65, p=0.003). After a Bonferroni correction was applied, there was still a significant association between rs1119692 and MTLE (corrected p=0.015). The frequency of the rs1119692-A allele was greater in patients (32.4%) than in control subjects (26.2%). Genotype analysis also showed an association for rs1119692 (uncorrected p=0.004, corrected p=0.02). CALHM1 rs1119692 variant might play a causal role in MTLE development independent of ApoEε4. The four-SNP haplotype (rs1119692-rs729211-rs2986016-rs2986017) showed the strongest association with MTLE (x2=19.87, p=0.0005). The G-G-G-T haplotype exhibited association with the increased risk of MTLE (OR=2.09,95%CI 1.27-3.42,p=0.0029) whereas the G-A-G-C haplotype was significantly associated with the reduced risk (OR=0.70,95%CI 0.53-0.92,p=0.0106). In addition, two-, three-, and five-SNP haplotype analysis also showed strong association with MTLE. In contrast with Alzheimer disease, no evidence of an association between rs2986017 and the risk for MTLE was found in our study. The other three SNPs (rs729211, rs2986018, rs2986016) did not show allelic or genotypic association with MTLE.ConclusionsThe ApoEε4 allele probably contributes to the development of MTLE in those patients with prior trauma. However, there were no significant association of ApoE and-491A/T polymorphisms with the increased risk of MTLE, onset of refractory MTLE, refractory complex partial seizures, and postictal confusion. CALHM1 rs1119692 variant may contribute to MTLE development independent of ApoE s4. Background and objectivesEpilepsy is one of the most common neurological disorders in children. The incidence and prevalence of childhood epilepsy (excluding febrile convulsion) in China is 1.51%o and 3.45%o, respectively. Therefore, epilepsy is one of the most important diseases that do great harm to physical and mental development of children. In recent years, considerable research shows the goal of childhood epilepsy treatment has been not only the control of epileptic seizures, but also an improvement of health-related quality of life (HRQOL). At present, although many scales can be used to assess the HRQOL of children with epilepsy, there are few epilepsy-specific questionnaires to evaluate the impact on the child's and the family's life. The impact of pediatric epilepsy scale (IPES) was developed to evaluate the impact on the family and the child of childhood epilepsy appropriately and efficiently. Since people from different countries have different economic and cultural backgrounds, the inventories developed in western countries may not have good reliability and validity when directly used in other countries. Thus, the aim of this study was to translate and to adapt the original version of IPES into a Chinese version, and to verify its reliability, validity, and sensitivity, which can provide a good measure for future psychological research and routine clinical care in China.MethodsThe IPES was translated into Chinese according to the procedure of the European Organization for Research and Treatment of Cancer Quality of Life Group. The eligible patients were selected strictly according to the inclusion and exclusion criterion. Convergent validity was assessed by analyzing the correlations between the translation and the subscales of the Chinese version of the Parent-Proxy Health-Related Quality of Life Measure for Children with Epilepsy (PPRS-QOLCE) as well as the impact of childhood epilepsy schedule. A principal components analysis, with a varimax rotation, was conducted to examine the construct of the measure. Cronbach's alpha coefficient was used to evaluate the internal consistency of the item and total scores. The intraclass correlation coefficient (ICC Model 2.1) was used to analyze the degree of agreement between test and retest scores at the item level. The sensitivity of the IPES was evaluated by examining the relationship between the mean score and epilepsy severity. ResultsThe main translational problems encountered in developing the Chinese version of IPES were due to the exact meaning of items and cross-cultural problems. One hundred and ten patients met the eligibility criteria. Under the supervision of the researcher, all eligible patients'parents completed the retest assessment. The subjects recruited completed all items in approximately 5 min (range:3-10 min). Mean item scores ranged from 0.30 to 2.82. All items contributed significantly to the summary measure. Considering the validity, all items were substantially correlated with the subscales with similar concept in PPRS-QOLCE and the impact of childhood epilepsy schedule. The principal components analysis indicated that three factors (outside activity participation, social well-being, home life) accounted for 72%of the variance of the scale. The internal consistency coefficients of the first and second test for the total were 0.916 and 0.930 respectively, and the test-retest reliability ranged from 0.891 to 0.992. Additionally, the IPES can detect the differences in HRQOL between the subjects according to epilepsy severity, which has good sensitivity.ConclusionsAfter a multistage translation and cultural adaptation, psychometric analysis suggests the Chinese version of IPES exhibits appropriate validity, excellent internal consistency and test-retest reliability, and good sensitivity, supporting its usefulness as an accurate, acceptable and brief measurement tool that reflects the way that childhood epilepsy affects the child's and family's HRQOL in China. Future psychological research and routine clinical care will undoubtedly benefit from the use of this measure.