title: Ethnicity and Smoking-Associated DNA Methylation Changes at HIV Co-Receptor GPR15.
abstract: Smoking is associated with poorer health outcomes for both African and European Americans. In order to better understand whether ethnic-specific genetic variation may underlie some of these differences, we compared the smoking-associated genome-wide methylation signatures of African Americans with those of European Americans, and followed up this analysis with a focused examination of the most ethnically divergent locus, cg19859270, at the GPR15 gene. We examined the association of methylation at this locus to the rs2230344 SNP and GPR15 gene and protein expression. Consistent with prior analyses, AHRR residue cg05575921 was the most differentially methylated residue in both African Americans and European Americans. However, the second most differentially methylated locus in African Americans, cg19859270, was only modestly differentially methylated in European Americans. Interrogation of the methylation status of this CpG residue found in GPR15, a chemokine receptor involved in HIV pathogenesis, showed a significant interaction of ethnicity with smoking as well as a marginal effect of genotype at rs2230344, a neighboring non-synonymous SNP, but only among African Americans. Gene and protein expression analyses showed that demethylation at cg19859270 was associated with an increase in both mRNA and protein levels. Since GPR15 is involved in the early stages of viral replication for some HIV-1 and HIV-2 isolates, and the prevalence of HIV is increased in African Americans and smokers, these data support a possible role for GPR15 in the ethnically dependent differential prevalence of HIV.
authors.affiliation: Department of Biomedical Engineering, University of Iowa , Iowa City, IA , USA ; Department of Psychiatry, University of Iowa , Iowa City, IA , USA.
authors.forename: Meeshanthini V
authors.initials: MV
authors.lastname: Dogan
authors.affiliation: Department of Internal Medicine, University of Iowa , Iowa City, IA , USA ; Iowa City Veterans Affairs , Iowa City, IA , USA.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Center for Family Research, University of Georgia , Athens, GA , USA.
authors.forename: Steven R H
authors.initials: SR
authors.lastname: Beach
authors.affiliation: Department of Psychology, Iowa State University , Ames, IA , USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Cutrona
authors.affiliation: Department of Psychology, University of Connecticut , Storrs, CT , USA.
authors.forename: Frederick X
authors.initials: FX
authors.lastname: Gibbons
authors.affiliation: Center for Family Research, University of Georgia , Athens, GA , USA.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Simons
authors.affiliation: Center for Family Research, University of Georgia , Athens, GA , USA.
authors.forename: Gene H
authors.initials: GH
authors.lastname: Brody
authors.affiliation: Department of Internal Medicine, University of Iowa , Iowa City, IA , USA ; Iowa City Veterans Affairs , Iowa City, IA , USA.
authors.forename: Jack T
authors.initials: JT
authors.lastname: Stapleton
authors.affiliation: Department of Biomedical Engineering, University of Iowa , Iowa City, IA , USA ; Department of Psychiatry, University of Iowa , Iowa City, IA , USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Philibert
keywords: AHRR; African Americans; European Americans; GPR15; HIV; epigenetics; ethnicity; smoking