School of Medicine and Health Sciences Poster Presentations

Title

Effect of genetic variation in GSTP1 and AXIN1 on bone mineral density in children and young adults

Poster Number

116

Document Type

Poster

Status

Medical Student

Abstract Category

Basic Biomedical Sciences

Keywords

AXIN1, GSTP1, bone mineral density, sexual dimorphism, SNP

Publication Date

Spring 2018

Abstract

Background:

The Glutathione S-transferase P 1 (GSTP1) family of enzymes minimize oxidative cellular damage which adversely affect bone health. Studieshave shown that variation at rs1695 in GSTP1 negatively impacts BMD. Another determinant in bone quality is the canonical-Wnt pathway in which the AXIN1 protein functions as a negative regulator. Previous studies have associated the rs9921222 variant of AXIN1 with lower total BMD/osteoporosis.

Objective:

To expand our understanding of the influence of rs1695 and rs9921222 on BMD.

Methods:

DNA samples from the Bone Health (African-American) cohort and a Caucasian sub-cohort of the Assessing Inherited Markers of Metabolic Syndrome in the Young (AIMMY) were utilized to measure total BMD without head z-score (adjusted for height) and total BMD, respectively. Illumina Multi-Ethnic Genotyping Array (MEGA) chip and Applied Biosystems Taqman allelic discrimination assays/Real-Time PCR were utilized for the Bone Health and AIMMY cohorts, respectively. ANCOVA models where genotype was the dependent variable, appropriate phenotype the independent variable, and age (for Bone Health) or age and height (for AIMMY) as covariates were utilized.

Results:

A statistically significant association between total BMD and rs1695 was observed in males of the AIMMY Caucasian cohort (p=0.047). No significant association between the homozygous GG variant of rs1695 and total BMD was found. No statistically significant genotype-phenotype associations between rs9921222 or rs1695 and total BMD were present in the Bone Health cohort using an additive genetic model. There was no reported association between total BMD and the rs1695 GG homozygote variant.

Discussion:

Significant differences in the association of genetic variants of rs1695 and BMD in both the AIMMY and Bone Health cohorts could be influenced by race/ethnicity- both of which have been significantly associated with bone quality/fracture risk. The significant association present in Caucasian males of the AIMMY cohort (p=0.047) but not in females (p = 0.33) underscores the important role of sexual dimorphism in determining musculoskeletal phenotypes. The presence of the rs1695 G allele variant in GSTP1 could indicate appreciable build-up of ROS in males and subsequently result in lower quality of bone.

Our work did not find a significant association with rs9921222 and total BMD or BMD z-score minus head. Conflicting results with previous studies could be attributed to the highly polygenic nature of BMD. It is plausible that rs9921222 may be inherited with other SNPs that are associated with lower BMD. The present study could not account for confounding SNPs that may have been inherited along with rs9921222.

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Effect of genetic variation in GSTP1 and AXIN1 on bone mineral density in children and young adults

Background:

The Glutathione S-transferase P 1 (GSTP1) family of enzymes minimize oxidative cellular damage which adversely affect bone health. Studieshave shown that variation at rs1695 in GSTP1 negatively impacts BMD. Another determinant in bone quality is the canonical-Wnt pathway in which the AXIN1 protein functions as a negative regulator. Previous studies have associated the rs9921222 variant of AXIN1 with lower total BMD/osteoporosis.

Objective:

To expand our understanding of the influence of rs1695 and rs9921222 on BMD.

Methods:

DNA samples from the Bone Health (African-American) cohort and a Caucasian sub-cohort of the Assessing Inherited Markers of Metabolic Syndrome in the Young (AIMMY) were utilized to measure total BMD without head z-score (adjusted for height) and total BMD, respectively. Illumina Multi-Ethnic Genotyping Array (MEGA) chip and Applied Biosystems Taqman allelic discrimination assays/Real-Time PCR were utilized for the Bone Health and AIMMY cohorts, respectively. ANCOVA models where genotype was the dependent variable, appropriate phenotype the independent variable, and age (for Bone Health) or age and height (for AIMMY) as covariates were utilized.

Results:

A statistically significant association between total BMD and rs1695 was observed in males of the AIMMY Caucasian cohort (p=0.047). No significant association between the homozygous GG variant of rs1695 and total BMD was found. No statistically significant genotype-phenotype associations between rs9921222 or rs1695 and total BMD were present in the Bone Health cohort using an additive genetic model. There was no reported association between total BMD and the rs1695 GG homozygote variant.

Discussion:

Significant differences in the association of genetic variants of rs1695 and BMD in both the AIMMY and Bone Health cohorts could be influenced by race/ethnicity- both of which have been significantly associated with bone quality/fracture risk. The significant association present in Caucasian males of the AIMMY cohort (p=0.047) but not in females (p = 0.33) underscores the important role of sexual dimorphism in determining musculoskeletal phenotypes. The presence of the rs1695 G allele variant in GSTP1 could indicate appreciable build-up of ROS in males and subsequently result in lower quality of bone.

Our work did not find a significant association with rs9921222 and total BMD or BMD z-score minus head. Conflicting results with previous studies could be attributed to the highly polygenic nature of BMD. It is plausible that rs9921222 may be inherited with other SNPs that are associated with lower BMD. The present study could not account for confounding SNPs that may have been inherited along with rs9921222.