CD14 (C-260T) polymorphism is not associated with sudden infant death syndrome (SIDS) in a large South Australian cohort

Abstract

Similarities have been drawn between models of endotoxic shock and gross and microscopic pathology observed in sudden infant death syndrome (SIDS) cases. Polymorphisms in genes that influence the expression of endotoxin receptors could affect the outcome of toxaemia, and could, therefore, play a role in SIDS. The CD14 gene promoter contains a single nucleotide polymorphism that affects the level of CD14 gene expression. The TT genotype of the CD14 (C-260T) polymorphism causes a significantly higher density of CD14 receptor expression on monocytes which makes the individual more sensitive to endotoxin than those with the wild-type (CC). This investigation was designed to determine whether SIDS infants have a higher frequency of the CD14 (C-260T) polymorphism compared with non-SIDS controls. One hundred and sixteen SIDS and 228 control infants were genotyped using PCR followed by restriction fragment length analysis of amplified product. Carriage of the TT or CT genotypes did not significantly differ between SIDS and control infants (P = 0.218 and 0.081, respectively). The frequencies observed in the control group were consistent with Hardy—Weinberg equilibrium and did not differ significantly from the published frequencies in Caucasian Australians. These results suggest that CD14 (C-260T) polymorphism is unlikely to be implicated in SIDS.

Keywords

CD14 endotoxin genetic polymorphism polymerase chain reaction sudden infant death syndrome SIDS

References

Blood-Siegfried J. , Rambaud C. , Nyska A. , Germolec D. Evidence for infection, inflammation and shock in sudden infant death: parallels between a neonatal rat model of sudden death and infants who died of sudden infant death syndrome. Innate Immun 2008; 14: 145-152.

Rambaud C. , Guibert M. , Briand E. , Grangeot-Keros L. , CoulombL’Hermine A. , Dehan M. Microbiology in sudden infant death syndrome (SIDS) and other childhood deaths . FEMS Immunol Med Microbiol 1999; 25: 59-66.

Bochud P. , Calandra T. Science, medicine, and the future. Pathogenesis of sepsis: new concepts and implications for future treatment. BMJ 2003 ; 326: 262-266.

Hubacek J. , Pit’ha J. , Skodova Z. , Stanek V. , Poledne R. C(-260)T polymorphism in the promotor of the CD14 monocyte receptor gene as a risk factor for myocardial infarction. Circulation 1999; 99: 3218-3220.

Morange P. , Saut N. , Alessi M. et al. Interaction between the C260T polymorphism of the CD14 gene and the plasma IL-6 concentration on the risk of myocardial infarction: the HIFMECH study. Atherosclerosis 2005; 179: 317-323.

Lin J. , Yao Y. , Yu Y. et al. Effects of CD14-159 C/T polymorphism on CD14 expression and the balance between pro-inflammatory and anti-inflammatory cytokines in whole blood culture. Shock 2007; 28: 148-153.

Vege A. , Rognum TO , Scott H. , Aasen AO , Saugstad OD SIDS cases have increased levels of interleukin-6 in cerebrospinal fluid. Acta Paediatr 1995; 84: 193-196.

Beckwith J. Discussion of terminology and definition of sudden infant death syndrome. In: Bergman A , Beckwith J , Ray C. (eds). Sudden infant death syndrome: Proceedings of the second international conference on causes of sudden death in infants. Seattle, WA: University of Washington Press, 1970; 18.

Willinger M. , James LS , Catz C. Defining the sudden infant death syndrome (SIDS): deliberations of an expert panel convened by the National Institute of Child Health and Human Development. Pediatr Pathol 1991; 11: 677-684.

10.

Krous H. , Beckwith J. , Byard R. et al. Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach. Pediatrics 2004; 114: 234-238.

11.

Lichy C. , Meiser H. , Grond-Ginsbach C. , Buggle F. , Dörfer C. , Grau A. Lipopolysaccharide receptor CD14 polymorphism and risk of stroke in a South-German population. J Neurol 2002; 249: 821-823.

12.

Kedda M. -A, Lose F. , Duffy D. , Bell E. , Thompson P. , Upham J. The CD14 C-159T polymorphism is not associated with asthma or asthma severity in an Australian adult population. Thorax 2005; 60: 211-214.

13.

Panchal R. , Ulrich R. , Bradfute S. et al. Reduced expression of CD45 protein-tyrosine phosphatase provides protection against anthrax pathogenesis. J Biol Chem 2009; 284: 12874-12885.

14.

Härtel C. , Finas D. , Ahrens P. et al. Polymorphisms of genes involved in innate immunity: association with preterm delivery. Mol Hum Reprod 2004; 10: 911-915.

15.

Härtel C. , Rupp J. , Hoegemann A. et al. 159C>T CD14 genotype - functional effects on innate responses in term neonates. Hum Immunol 2008; 69: 338-343.

16.

Guerra S. , Lohman C. , LeVan T. , Wright A. , Martinez F. , Halonen M. The differential effect of genetic variation on soluble CD14 levels in human plasma and milk. Am J Reprod Immunol 2004; 52: 204-211.

17.

Labéta M. , Vidal K. , Rey Nores J. et al. Innate recognition of bacteria in human milk is mediated by a milk-derived highly expressed pattern recognition receptor, soluble CD14. J Exp Med 2000; 191: 1807-1812.

18.

Bettelheim K. , Goldwater P. , Dwyer B. , Bourne A. , Smith D. Toxigenic Escherichia coli associated with sudden infant death syndrome. Scand J Infect Dis 1990; 22: 467-476.

19.

Bettiol SS , Radcliff FJ , Hunt AL , Goldsmid JM Bacterial flora of Tasmanian SIDS infants with special reference to pathogenic strains of Escherichia coli. Epidemiol Infect 1994; 112: 275-284.

20.

Vennemann M. , Bajanowski T. , Brinkmann B. et al. Does breastfeeding reduce the risk of sudden infant death syndrome? Pediatrics 2009; 123: 406-410.

21.

Marchant A. , Duchow J. , Delville J-P. , Goldman M. Lipopolysaccharide induces up-regulation of CD14 molecule on monocytes in human whole blood. Eur J Immunol 1992; 22: 1663-1665.