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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.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.These data indicate that genetic variation in Hp may affect susceptibility to active trachoma differentially by sex in The Gambia.

Original publication

DOI

10.1371/journal.pone.0011075

Type

Journal article

Journal

PloS one

Publication Date

11/06/2010

Volume

5

Addresses

MRC International Nutrition Group, London School of Hygiene & Tropical Medicine, London, UK.

Keywords

Humans, Trachoma, Anemia, Sickle Cell, Genetic Predisposition to Disease, Haptoglobins, DNA Primers, Risk Factors, Cross-Sectional Studies, Polymerase Chain Reaction, Base Sequence, Haplotypes, Polymorphism, Single Nucleotide, Child, Child, Preschool, Infant, Rural Population, Female, Male