ABSTRACT
<p><b>OBJECTIVE</b>To explore clinical, genetic and molecular features of two Chinese Han families with Leber's hereditary optic neuropathy (LHON).</p><p><b>METHODS</b>Ophthalmologic examinations revealed variable severity and age-at-onset of visual loss among probands and other matrilineal relatives of both families. The families exhibited extremely low penetrance of visual impairment. The entire mitochondrial genome of two probands was amplified by PCR in 24 overlapping fragments using sets of oligonucleotide primers.</p><p><b>RESULTS</b>Sequence analysis of complete mitochondrial genome in the pedigrees excluded three common LHON associated mutations G11778A, G3460A and T14484C, but revealed the presence of a known homoplasmic tRNA(Thr) A15951G mutation. It also showed distinct sets of mtDNA polymorphisms belonging to Eastern Asian haplogroup D4b1. The A15951G mutation is located at the extremely conserved nucleotide (conventional position 71) of tRNA(Thr). Thus, this mutation may alter the structure and stability of mitochondrial tRNA(Thr), thereby leading to a failure in the tRNA metabolism and mitochondrial dysfunction, causing visual impairment.</p><p><b>CONCLUSION</b>The results suggested that the A15951G mutation might be involved in the pathogenesis of Leber's hereditary optic neuropathy in the two families.</p>
Subject(s)
Adolescent , Child , Humans , Male , Asian People , Genetics , Base Sequence , Mitochondria , Genetics , Molecular Sequence Data , Mutation , Genetics , Optic Atrophy, Hereditary, Leber , Genetics , Pedigree , RNA, Transfer, Thr , Genetics , Sequence AlignmentABSTRACT
<p><b>OBJECTIVE</b>To understand the environmental risk factors on attempted suicide in patients with major depression, and to study the interaction between factors as single nucleotide polymorphism(SNP) of TPH2 gene rs7305115 associated to attempted suicide in major depression.</p><p><b>METHODS</b>Paired case-control study on 215 suicide attempters with major depression (92 male, 123 female) and molecular biological techniques were used to study the relation between TPH2 gene rs7305115 SNP,interrelated environmental factors and the rate of attempted suicide. Controls were paired with cases according to the same gender, similar age (no more than 3 years) and from the same district.</p><p><b>RESULTS</b>There were remarkably significant differences in gene types and gene frequency between case and control groups (P < 0.001). Data from multivariate conditional logistic regression model analysis showed that hopelessness, negative life-events and family history of suicide were relationship of attempted suicide in patients with major depression with OR values as 0.33 (95% CI: 0.22-0.99), 7.68 (95% CI: 5.79-13.74), 6.64 (95% CI: 2.48-11.04), 2.98 (95% CI: 1.17-5.04) respectively. There was no first level interaction between any of the two risk factors.</p><p><b>CONCLUSION</b>Results from the study supported the idea that hopelessness, negative life-events and family history of suicide were risk factors of attempted suicide in major deprbssion while TPH2 gene rs7305115 A/A might be the protective factor.</p>
Subject(s)
Humans , Case-Control Studies , China , Epidemiology , Depressive Disorder, Major , Genetics , Psychology , Odds Ratio , Polymorphism, Single Nucleotide , Risk Factors , Suicide, Attempted , Psychology , Tryptophan Hydroxylase , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To assess the associations between schizophrenia and six functional genes: dopamine D2 receptor gene (DRD2), dopamine D4 receptor gene (DRD4), 5-hydroxytryptamine 2A receptor gene (5-HT2A), 5-HT6 receptor gene (5-HT6), catechol-O-methyltransferase gene (COMT) and dopamine transporter gene (DAT1).</p><p><b>METHODS</b>With the techniques of Amp-RFLP and Amp-FLP, association analysis was made between schizophrenia and the six genes in 67 schizophrenic patients from Chinese Han population.</p><p><b>RESULTS</b>(1) Neither genotypes nor alleles of DRD2, 5-HT2A, 5-HT6 and COMT gene showed significant differences between patients and controls (P>0.05). (2) Six repeats (6R) in DRD4 gene, the allele of 480 bp and the genotype of 480/520 in DAT1 gene were found to be of significant differences between the two groups (P<0.05). (3) Only one negative association was observed between the 480 bp allele of DAT1 gene and schizophrenia (OR=0.441, 95% CI:0.202-0.963, Z=2.05, P<0.05).</p><p><b>CONCLUSION</b>The 480 bp allele of DAT1 gene is negatively associated with schizophrenia in Chinese Han population, which stands for the dopamine hypothesis of schizophrenia.</p>