Genes regulating the serotonin metabolic pathway in the brain stem and their role in the etiopathogenesis of the sudden infant death syndrome
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 respon...
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Veröffentlicht in: | Genomics (San Diego, Calif.) Calif.), 2008-06, Vol.91 (6), p.485-491 |
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Zusammenfassung: | 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. |
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ISSN: | 0888-7543 1089-8646 |
DOI: | 10.1016/j.ygeno.2008.01.010 |