Electronic Theses and Dissertations

Identifier

6300

Date

2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Public Health

Committee Chair

Wilfried Karmaus

Committee Member

Hongmei Zhang

Committee Member

John Holloway

Committee Member

Syed Hasan Arshad

Committee Member

Thomas R. Sutter

Abstract

Prior studies linking breastfeeding duration and maternal gestational smoking, respectively, to offspring eczema report contradictory findings. However, it is not known whether maternal gestational smoking and breastfeeding duration can jointly influence eczema and whether these exposures mediate their effect on eczema via DNA Methylation (DNA-M) of CpG (cytosine-phosphate-guanine) sites. With data from the Isle of Wight (IOW) birth cohort, UK, we first evaluated the combined effect of maternal gestational smoking and breastfeeding duration on eczema at ages 1-to-2 (n=980), 4 (n=902), 10 (n=966), and 18 years (n=929) using Generalized estimating equations (GEE). We found a protective effect of longer duration of breastfeeding (weeks) on eczema if the mother smoked during gestation (objective (i)). The risk ratios (95% CI) for eczema related to maternal gestational smoking for 3, 9, 15, 21 weeks of breastfeeding were 0.88 (0.66, 1.20), 0.74 (0.54, 1.01), 0.62 (0.41, 0.93), and 0.51 (0.3, 0.88), respectively. Next, we investigated whether DNA-M at age 10 can mediate the effect of breastfeeding duration on eczema at age 18 (n=276) using linear, log linear regression and structural equation modelling. The CpGs cg03605610 (between NRC2 and LINC01276), cg04928096 (AXIN1), cg26375057 (ZIC1) and cg26979504 (HHEX) were in the causal pathway between duration of breastfeeding and eczema mediating its protective effect (indirect effect estimate: -0.008, p-value: 0.022 (cg03605610); Estimate: -0.008, p-value: 0.049 (cg04928096); Estimate: -0.008, p-value: 0.034 (cg26375057); Estimate: -0.007, p-value: 0.021 (cg26979504)). Finally, we evaluated whether DNA-M at age 10 associated with combined effect of gestational smoking and duration of breastfeeding can explain the risk of eczema using linear and log linear regression. We found cg07208825 (ALMS1P), cg12954512 (Intergenic) and cg21601919 (FGF18) to be associated with duration of breastfeeding if the mother smoked during gestation (Estimate: -0.006, p-value: 0.046 (cg07208825); Estimate: 0.021, p-value: 0.036 (cg12954512); estimate: 0.008, p-value: 0.016 (cg21601919). These CpGs were also associated with eczema at age 18 (Risk-ratio: 14.23, p-value: 1.27E-07 (cg07208825); Risk-ratio: 0.62, p-value: 3.90E-03 (cg12954512); Risk-ratio: 0.18, p-value: 1.56E-06 (cg21601919). Future studies are required to corroborate these findings, and understand how the breastmilk composition if the mother smoked during pregnancy influences these genes affecting eczema pathogenesis.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to the local University of Memphis Electronic Theses & dissertation (ETD) Repository.

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