Dataset Information

Haptoglobin and sickle cell polymorphisms and risk of active trachoma in Gambian children.

ABSTRACT: 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. METHODOLOGY AND PRINCIPAL FINDINGS: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.

SUBMITTER: Savy M

PROVIDER: S-EPMC2884021 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Haptoglobin and sickle cell polymorphisms and risk of active trachoma in Gambian children.

Savy Mathilde M 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

PloS one 20100611 6

<h4>Background</h4>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 funct ...[more]

PMID: 20552021

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Project description:BackgroundActive trachoma is not uniformly distributed in endemic areas, and local environmental factors influencing its prevalence are not yet adequately understood. Determining whether clustering is a consistent phenomenon may help predict likely modes of transmission and help to determine the appropriate level at which to target control interventions. The aims of this study were, therefore, to disentangle the relative importance of clustering at different levels and to assess the respective role of individual, socio-demographic, and environmental factors on active trachoma prevalence among children in Mali.Methodology/principal findingsWe used anonymous data collected during the Mali national trachoma survey (1996-1997) at different levels of the traditional social structure (14,627 children under 10 years of age, 6,251 caretakers, 2,269 households, 203 villages). Besides field-collected data, environmental variables were retrieved later from various databases at the village level. Bayesian hierarchical logistic models were fit to these prevalence and exposure data. Clustering revealed significant results at four hierarchical levels. The higher proportion of the variation in the occurrence of active trachoma was attributable to the village level (36.7%), followed by household (25.3%), and child (24.7%) levels. Beyond some well-established individual risk factors (age between 3 and 5, dirty face, and flies on the face), we showed that caretaker-level (wiping after body washing), household-level (common ownership of radio, and motorbike), and village-level (presence of a women's association, average monthly maximal temperature and sunshine fraction, average annual mean temperature, presence of rainy days) features were associated with reduced active trachoma prevalence.Conclusions/significanceThis study clearly indicates the importance of directing control efforts both at children with active trachoma as well as those with close contact, and at communities. The results support facial cleanliness and environmental improvements (the SAFE strategy) as population-health initiatives to combat blinding trachoma.

Project description:Background: Anaemia is a major public health concern especially in African children living in malaria-endemic regions. Interferon-gamma (IFN-γ) is elevated during malaria infection and is thought to influence erythropoiesis and iron status. Genetic variants in the IFN-γ gene (IFNG) are associated with increased IFN-γ production. We investigated putative functional single nucleotide polymorphisms (SNPs) and haplotypes of IFNG in relation to nutritional iron status and anaemia in Gambian children over a malaria season. Methods: We used previously available data from Gambian family trios to determine informative SNPs and then used the Agena Bioscience MassArray platform to type five SNPs from the IFNG gene in a cohort of 780 Gambian children aged 2-6 years. We also measured haemoglobin and biomarkers of iron status and inflammation at the start and end of a malaria season. Results: We identified five IFNG haplotype-tagging SNPs ( IFNG-1616 [rs2069705], IFNG+874 [rs2430561], IFNG+2200 [rs1861493], IFNG+3234 [rs2069718] and IFNG+5612 [rs2069728]). The IFNG+2200C [rs1861493] allele was associated with reduced haemoglobin concentrations (adjusted β -0.44 [95% CI -0.75, -0.12]; Bonferroni adjusted P = 0.03) and a trend towards iron deficiency compared to wild-type at the end of the malaria season in multivariable models adjusted for potential confounders. A haplotype uniquely identified by IFNG+2200C was similarly associated with reduced haemoglobin levels and trends towards iron deficiency, anaemia and iron deficiency anaemia at the end of the malaria season in models adjusted for age, sex, village, inflammation and malaria parasitaemia. Conclusion: We found limited statistical evidence linking IFNG polymorphisms with a risk of developing iron deficiency and anaemia in Gambian children. More definitive studies are needed to investigate the effects of genetically influenced IFN-γ levels on the risk of iron deficiency and anaemia in children living in malaria-endemic areas.

Dataset Information

Haptoglobin and sickle cell polymorphisms and risk of active trachoma in Gambian children.

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Haptoglobin and sickle cell polymorphisms and risk of active trachoma in Gambian children.

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