Limits...
Ethnicity and Smoking-Associated DNA Methylation Changes at HIV Co-Receptor GPR15.

Dogan MV, Xiang J, Beach SR, Cutrona C, Gibbons FX, Simons RL, Brody GH, Stapleton JT, Philibert RA - Front Psychiatry (2015)

Bottom Line: 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.Gene and protein expression analyses showed that demethylation at cg19859270 was associated with an increase in both mRNA and protein levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, University of Iowa , Iowa City, IA , USA ; Department of Psychiatry, University of Iowa , Iowa City, IA , USA.

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.

No MeSH data available.


Related in: MedlinePlus

Position of Illumina GPR15 methylation probes. The position of Illumina GPR15 methylation probes per the UCSC Genome Browser (http://genome.ucsc.edu). The genome-wide corrected p-values for the CpG residue probes are p-value <0.90, p-value <0.39, p-value <0.10, and p-value <6.2E−05, respectively (left to right).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4585036&req=5

Figure 1: Position of Illumina GPR15 methylation probes. The position of Illumina GPR15 methylation probes per the UCSC Genome Browser (http://genome.ucsc.edu). The genome-wide corrected p-values for the CpG residue probes are p-value <0.90, p-value <0.39, p-value <0.10, and p-value <6.2E−05, respectively (left to right).

Mentions: Since our initial analyses seemed to confirm our prior impressions that GPR15 was more prominently differentially methylated in African American smokers, we focused our inquiry on GPR15. Figure 1 illustrates key features of this chromosome 3 locus. GPR15 is a single exon gene coding for 1254-bp mRNA and a 360 amino acid protein. Overall, the gene region is sparsely populated with CpG residues (19 CpG residues in the 2300-bp region covering the gene region). There are four probes in the Illumina 450K array covering GPR15, cg26385013 (TSS1500), cg08375941 (TSS1500), cg19859270 (first Exon), and cg19614811 (TSS200). In contrast to the strong signal at cg19859270, methylation at the other three GPR15 CpG residues is not significantly associated with smoking status [cg26385013 (p-value <0.90), cg08375941 (p-value <0.39), and cg19614811 (p-value <0.10)].


Ethnicity and Smoking-Associated DNA Methylation Changes at HIV Co-Receptor GPR15.

Dogan MV, Xiang J, Beach SR, Cutrona C, Gibbons FX, Simons RL, Brody GH, Stapleton JT, Philibert RA - Front Psychiatry (2015)

Position of Illumina GPR15 methylation probes. The position of Illumina GPR15 methylation probes per the UCSC Genome Browser (http://genome.ucsc.edu). The genome-wide corrected p-values for the CpG residue probes are p-value <0.90, p-value <0.39, p-value <0.10, and p-value <6.2E−05, respectively (left to right).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585036&req=5

Figure 1: Position of Illumina GPR15 methylation probes. The position of Illumina GPR15 methylation probes per the UCSC Genome Browser (http://genome.ucsc.edu). The genome-wide corrected p-values for the CpG residue probes are p-value <0.90, p-value <0.39, p-value <0.10, and p-value <6.2E−05, respectively (left to right).
Mentions: Since our initial analyses seemed to confirm our prior impressions that GPR15 was more prominently differentially methylated in African American smokers, we focused our inquiry on GPR15. Figure 1 illustrates key features of this chromosome 3 locus. GPR15 is a single exon gene coding for 1254-bp mRNA and a 360 amino acid protein. Overall, the gene region is sparsely populated with CpG residues (19 CpG residues in the 2300-bp region covering the gene region). There are four probes in the Illumina 450K array covering GPR15, cg26385013 (TSS1500), cg08375941 (TSS1500), cg19859270 (first Exon), and cg19614811 (TSS200). In contrast to the strong signal at cg19859270, methylation at the other three GPR15 CpG residues is not significantly associated with smoking status [cg26385013 (p-value <0.90), cg08375941 (p-value <0.39), and cg19614811 (p-value <0.10)].

Bottom Line: 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.Gene and protein expression analyses showed that demethylation at cg19859270 was associated with an increase in both mRNA and protein levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, University of Iowa , Iowa City, IA , USA ; Department of Psychiatry, University of Iowa , Iowa City, IA , USA.

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.

No MeSH data available.


Related in: MedlinePlus