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, pb0.001) 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 (pb0.001). 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.

Genes regulating the serotonin metabolic pathway in the brain stem and their role in the etiopathogenesis of the Sudden Infant Death Syndrome / NONNIS MARZANO, Francesco; Maldini, M; Filonzi, L; LAVEZZI A., M; Parmigiani, S; Magnani, Cinzia; Bevilacqua, Giulio; Matturri, L.. - In: GENOMICS. - ISSN 0888-7543. - 91:(2008), pp. 485-491. [10.1016/j.ygeno.2008.01.010]

Genes regulating the serotonin metabolic pathway in the brain stem and their role in the etiopathogenesis of the Sudden Infant Death Syndrome

NONNIS MARZANO, Francesco;FILONZI L;MAGNANI, Cinzia;BEVILACQUA, Giulio;
2008

Abstract

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, pb0.001) 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 (pb0.001). 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.
Genes regulating the serotonin metabolic pathway in the brain stem and their role in the etiopathogenesis of the Sudden Infant Death Syndrome / NONNIS MARZANO, Francesco; Maldini, M; Filonzi, L; LAVEZZI A., M; Parmigiani, S; Magnani, Cinzia; Bevilacqua, Giulio; Matturri, L.. - In: GENOMICS. - ISSN 0888-7543. - 91:(2008), pp. 485-491. [10.1016/j.ygeno.2008.01.010]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/1860515
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