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27: Mannose binding lectin haplotypes are associated with cerebral palsy

      Objective

      To investigate associations between infection, polymorphisms in the mannose binding lectin gene (MBL) & cerebral palsy (CP) in a large Caucasian population-based study.

      Study design

      Case-control study using newborn screening card DNA of 443 CP cases & 883 controls to screen for 6 polymorphisms in the MBL gene (−550, −221, +4, exon-1 codons 52, 54, 57).These polymorphisms combine to create “haplotypes” of high (HYPA), intermediate (LYQA, LYPA), low (LXPA) & defective (HYPD, LYQC, LYPB) circulating MBL levels.

      Results

      χ2 analyses demonstrated significant differences in MBL haplotype between CP cases & controls (CP <37 wks gestational age (GA) χ2 14.99, p=0.02; <32 wks GA χ2 13.62, p=0.02). The table below demonstrates significant associations observed for specific haplotypes. Subanalysis on samples previously testing positive for exposure to viral infection demonstrated similar significance patterns, whilst analysis on samples negative for exposure to viral infection showed no positive associations between MBL haplotypes & CP.
      Tabled 1Significant associations (p<0.05) between MBL haplotype, CP type, GA & exposure to infection
      CP TypeMBL HaplotypeGA (wks)Infection StatusOdds Ratio (95% CI)
      AllLYPAAllNot considered1.57 (1.00–2.46)
      <372.43 (1.41–4.18)
      <322.54 (1.34–4.76)
      HemiplegiaLYPA<372.77 (1.02–7.26)
      <324.48 (1.55–12.65)
      QuadriplegiaHYPDAll3.47 (1.41–8.31)
      <327.86 (1.67–29.48)
      HemiplegiaLYPA<32Positive8.25 (1.08–52.76)
      QuadriplegiaHYPDAll5.24 (1.03–21.67)
      <3218.33 (2.06–150.68)

      Conclusion

      Carriage of the LYPA or HYPD haplotypes is associated with an increased risk of CP in the presence of exposure to viral infection & appears to act as a susceptibility factor for CP.