Haptoglobin and sickle cell polymorphisms and risk of active trachoma in Gambian children.
BACKGROUND
Susceptibility and resistance to trachoma, the leading infectious cause of blindness, have been associated with a range of host genetic factors. In vitro studies of the causative organism, Chlamydia trachomatis, demonstrate that iron availability regulates its growth, suggesting that host genes involved in regulating iron status and/or availability may modulate the risk of trachoma. The objective was to investigate whether haptoglobin (Hp) haplotypes constructed from the functional polymorphism (Hp1/Hp2) plus the functional promoter SNPs -61A-C (rs5471) and -101C-G (rs5470), or sickle cell trait (HbAS, rs334) were associated with risk of active trachoma when stratified by age and sex, in rural Gambian children.


RESULTS
In two cross sectional surveys of children aged 6-78 months (n = 836), the prevalence of the clinical signs of active trachoma was 21.4%. Within boys, haplotype E (-101G, -61A, Hp1), containing the variant allele of the -101C-G promoter SNP, was associated with a two-fold increased risk of active trachoma (OR = 2.0 [1.17-3.44]). Within girls, an opposite association was non-significant (OR = 0.58 [0.32-1.04]; P = 0.07) and the interaction by sex was statistically significant (P = 0.001). There was no association between trachoma and HbAS.


CONCLUSIONS
These data indicate that genetic variation in Hp may affect susceptibility to active trachoma differentially by sex in The Gambia.
Savy
Mathilde
M
MRC International Nutrition Group, London School of Hygiene & Tropical Medicine, London, UK.
Hennig
Branwen J
BJ
Doherty
Conor P
CP
Fulford
Anthony J
AJ
Bailey
Robin
R
Holland
Martin J
MJ
Sirugo
Giorgio
G
Rockett
Kirk A
KA
Kwiatkowski
Dominic P
DP
Prentice
Andrew M
AM
Cox
Sharon E
SE
D000755:Anemia, Sickle Cell / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012424:Rural Population; D014141:Trachoma / Q000235:genetics*
D017931:DNA Primers; D006242:Haptoglobins