Study On The Relationship Between NMDA Receptor Gene And Bipolar Disorder's Transmitting Disequilibration

Objective: to determine the molecular genetics relationship between three NMDA receptor gene and bipolar disorder, we collected 72 core family of bipolar affective disorder in Han people of China, applying such methods as transmitting disequilibration test, sibling pair disequilibration test and haplotyping, studied three polymorphism sites of NMDA receptor gene. Methods: 72 core family constellations of affective disorder were collected. We edited privately the family survey sheet according to genetics diagnostic test sheet provided by Harvard University, and extracted 216 cases of blood sample DNA in 72 families of han people, adopting CCMD-3 diagnosis standard. And we analyzed the transmit disequilibration between the three sites of NMDAR1 (1970-A/G) and affective disorder applying PCR and restriction enzymatic digestion approaches. We studied as follows: 1. investigation of core family constellations of affective disorder and quantitation assessment of various kinds phenotype after standard examinations; 2. three polymorphism sites were separately analyzed through such approaches as HHRR and TDT; 3. polymorphism sites were associated analyzed through such approaches as TDT and haplotyping, 4. it divided into groups according to clinical types, psychiatric symptom, age of onset of affective disorder, TDT and haplotyping were carded out. Results: Population statistics and clinical data of all subjects showed that there is no obvious difference between genders. In Hardy-Weinberg equilibration, 1970—A/G polymorphism, genotypic frequency AA=72.22%, AG=22.22%, GG=5.56%.Allele frequency of individual marker and results are summarized in table 2a. We found that G allele preferentially transmit to involved patients. The results of haplotyping are showed in table 2b.There are obvious linkage disequilibration among these polorphism in all samples and parent samples. Whereas not in the contracted samples.Conclusions: 1. There is linkage disequilibrium in 1970-A/G; there is no significant difference in genotype and gene frequency polymorphism site of patients and biological parents. 2. HHRR analysis showed that it probably correlate in 1970-A/G and affective disorder. 3. Single site TDT statistical analysis indicated there is transmitting disequilibration between the site and affective disorder, which hinting the site may be one of the risk factor of affective disorder.4. It has not been found the genotypic difference in patients of different clinical classification and those with psychiatric symptoms. 5. Different genotype of polymorphism genetic locus is minor associated with the age of onset, gender, attack frequency, clinical manifestation, and whether or not with psychiatric symptoms of affective disorder.