TY - JOUR
T1 - Sudden infant death syndrome
T2 - Association with a promoter polymorphism of the serotonin transporter gene
AU - Weese-Mayer, Debra E.
AU - Berry-Kravis, Elizabeth M.
AU - Maher, Brion S.
AU - Silvestri, Jean M.
AU - Curran, Mark E.
AU - Marazita, Mary L.
PY - 2003/3/15
Y1 - 2003/3/15
N2 - Serotonergic receptor binding in the arcuate nucleus, n. raphé obscurus, and other medullary regions is decreased in sudden infant death syndrome (SIDS) cases. Further, a variable tandem repeat sequence polymorphism in the promoter region of the serotonin transporter protein (5-HTT) gene has recently been associated with risk of SIDS in a Japanese cohort. This polymorphism differentially regulates 5-HTT expression, with the long allele (L), the SIDS-associated allele, being a more effective promoter than the short allele (S). We therefore investigated the 5-HTT promoter polymorphism in a cohort of 87 SIDS cases (43 African American and 44 Caucasian) and gender/ethnicitymatched controls. Significant positive associations were found between SIDS and the 5-HTT genotype distribution (P = 0.022), specifically with the L/L genotype (P = 0.048), and between SIDS and the 5-HTT L allele (P = 0.005). There was also a significant negative association between SIDS and the S/S genotype (P = 0.0 11). The comparisons were repeated in the African American and Caucasian subgroups. The data patterns were consistent in the subgroups, i.e., the L/L genotype and L allele were increased in the cases, but not all subgroup comparisons were statistically significant. These results indicate a relationship between SIDS and the L allele of the 5-HTT gene in African Americans and Caucasians, and if confirmed, will provide an important tool for identifying at-risk individuals and estimating the risk of recurrence.
AB - Serotonergic receptor binding in the arcuate nucleus, n. raphé obscurus, and other medullary regions is decreased in sudden infant death syndrome (SIDS) cases. Further, a variable tandem repeat sequence polymorphism in the promoter region of the serotonin transporter protein (5-HTT) gene has recently been associated with risk of SIDS in a Japanese cohort. This polymorphism differentially regulates 5-HTT expression, with the long allele (L), the SIDS-associated allele, being a more effective promoter than the short allele (S). We therefore investigated the 5-HTT promoter polymorphism in a cohort of 87 SIDS cases (43 African American and 44 Caucasian) and gender/ethnicitymatched controls. Significant positive associations were found between SIDS and the 5-HTT genotype distribution (P = 0.022), specifically with the L/L genotype (P = 0.048), and between SIDS and the 5-HTT L allele (P = 0.005). There was also a significant negative association between SIDS and the S/S genotype (P = 0.0 11). The comparisons were repeated in the African American and Caucasian subgroups. The data patterns were consistent in the subgroups, i.e., the L/L genotype and L allele were increased in the cases, but not all subgroup comparisons were statistically significant. These results indicate a relationship between SIDS and the L allele of the 5-HTT gene in African Americans and Caucasians, and if confirmed, will provide an important tool for identifying at-risk individuals and estimating the risk of recurrence.
KW - 5HTT
KW - Serotonin transporter
KW - Sudden infant deatlh syndrome
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U2 - 10.1002/ajmg.a.20005
DO - 10.1002/ajmg.a.20005
M3 - Article
C2 - 12599191
AN - SCOPUS:0037522034
SN - 1552-4825
VL - 117 A
SP - 268
EP - 274
JO - American Journal of Medical Genetics
JF - American Journal of Medical Genetics
IS - 3
ER -