Genes regulating the serotonin metabolic pathway in the brain stem and their role in the etiopathogenesis of the sudden infant death syndrome
详细信息 查看全文
- 作者：Francesco Nonnis Marzano ; Milena Maldini ; Laura Filonzi ; Anna Maria Lavezzi ; Stefano Parmigiani ; Cinzia Magnani ; Giulio Bevilacqua ; Luigi Matturri
- 关键词：5-HTT ; MAOA ; TPH2 ; Molecular polymorphisms ; SIDS ; Neurotransmitter
- 刊名：Genomics
- 出版年：2008
- 出版时间：June 2008
- 年：2008
- 卷：91
- 期：6
- 页码：485-491
- 全文大小：277 K
文摘
Genotypes and allelic frequencies of TPH2, 5-HTTLPR, the 5-HTT (SLC6A4) intron 2 variable-number tandem repeat (VNTR) region, and the MAOA VNTR region were determined in brain-stem samples of 20 “genuine” SIDS cases and compared with results obtained from 150 healthy controls. The SNP G1463A responsible for 80 % functionality loss of TPH2 (tryptophan hydroxylase 2) was not detected, neither in SIDS infants nor in the controls. In contrast, a strict relation was found between the 5-HTTLPR genotype and its allelic frequencies with SIDS cases. The L/L genotype and the long allele (L) of the promoter region of the serotonin transporter were significantly associated (likelihood ratio (LR) test, p < 0.001) with the syndrome (L/L, 60 % SIDS vs 14 % controls; L, 80 % SIDS vs 42.6 % controls). Polymorphisms of the intron 2 VNTR of the same gene showed a trend for significant differences between genotypes 10/10 and 12/12 (LR test, p = 0.068), with the L-12 haplotype being almost twofold in SIDS (44.5 % ) with respect to controls (23.4 % ). Differences were even higher considering the genotype combination L/L-12/12 (20 % SIDS vs 2.6 % ), and variations among categories were statistically highly significant (p < 0.001). Although additional differences were observed in the frequency of the MAOA (monoamine oxidase A) VNTR genotype 3R/3R between SIDS and controls (respectively 15 % vs 26 % ), the results were not supported by statistical significance. Molecular polymorphisms are discussed considering their functional role in regulating serotonin synthesis (TPH2), neuronal reuptake (5-HTTLPR and 5-HTT intron 2), and catabolism (MAOA) in the nervous system of Italian SIDS infants. Comparisons are made with previous data obtained in different ethnic groups.