Sex Differences in the Allele Distribution of PGLYRP2 Variant rs892145 in Parkinson’s Disease
Introduction. Parkinson’s disease (PD) is a complex multifactorial disease, involving genetic susceptibility, environmental risk factors, and gene-environmental interactions. The microbiota-gut-brain axis is hypothesized to play a role in the pathophysiology of PD, and peptidoglycan recognition prot...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-01-01
|
| Series: | Parkinson's Disease |
| Online Access: | http://dx.doi.org/10.1155/2023/6502727 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832558427197407232 |
|---|---|
| author | Caroline Ran Karin Wirdefeldt Olof Sydow Per Svenningsson Rochellys Diaz Heijtz |
| author_facet | Caroline Ran Karin Wirdefeldt Olof Sydow Per Svenningsson Rochellys Diaz Heijtz |
| author_sort | Caroline Ran |
| collection | DOAJ |
| description | Introduction. Parkinson’s disease (PD) is a complex multifactorial disease, involving genetic susceptibility, environmental risk factors, and gene-environmental interactions. The microbiota-gut-brain axis is hypothesized to play a role in the pathophysiology of PD, and peptidoglycan recognition proteins (PGLYRPs), which modulate the gut microbiota, are, therefore, relevant candidate genes for PD. Methods. Using quantitative real-time PCR, we genotyped three PGLYRP variants (rs892145, rs959117, and rs10888557) and performed an association analysis in 508 PD patients and 585 control individuals. We further conducted a meta-analysis of rs892145 and analyzed PGLYRP2 gene expression in lymphocytes from patients with PD and controls. Results. Although initial analysis of the three variants rs892145, rs959117, and rs10888557 and a meta-analysis of rs892145 did not reveal any association between the selected variants and PD, we found an interaction between sex and genotype for rs892145, with a marked difference in the allele distribution of rs892145 between male and female patients. As compared to controls, the T allele was less common in female patients (odds ratio = 0.76, P = 0.04) and more common in male patients (odds ratio = 1.29, P = 0.04). No difference was found in PGLYRP2 gene expression between PD patients and controls (P = 0.38), nor between sexes (P = 0.07). Discussion. Overall, this genetic screening in Swedish PD patients does not support previous results demonstrating associations of PGLYRP variants with the risk of PD. Meta-analysis of rs892145 revealed pronounced heterogeneity between previously published studies which is likely to have influenced the results. Taken together, the genetic and gene expression analyses suggest a possible link between genetic variants in PGLYRP2 and sex differences in PD. Because of the limited sample size in our study, these results need to be verified in independent cohorts before concluding. |
| format | Article |
| id | doaj-art-0105013703414158a400e9a034f43695 |
| institution | Kabale University |
| issn | 2042-0080 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Parkinson's Disease |
| spelling | doaj-art-0105013703414158a400e9a034f436952025-02-03T01:32:19ZengWileyParkinson's Disease2042-00802023-01-01202310.1155/2023/6502727Sex Differences in the Allele Distribution of PGLYRP2 Variant rs892145 in Parkinson’s DiseaseCaroline Ran0Karin Wirdefeldt1Olof Sydow2Per Svenningsson3Rochellys Diaz Heijtz4Department of NeuroscienceDepartment of Clinical NeuroscienceDepartment of Clinical NeuroscienceDepartment of Clinical NeuroscienceDepartment of NeuroscienceIntroduction. Parkinson’s disease (PD) is a complex multifactorial disease, involving genetic susceptibility, environmental risk factors, and gene-environmental interactions. The microbiota-gut-brain axis is hypothesized to play a role in the pathophysiology of PD, and peptidoglycan recognition proteins (PGLYRPs), which modulate the gut microbiota, are, therefore, relevant candidate genes for PD. Methods. Using quantitative real-time PCR, we genotyped three PGLYRP variants (rs892145, rs959117, and rs10888557) and performed an association analysis in 508 PD patients and 585 control individuals. We further conducted a meta-analysis of rs892145 and analyzed PGLYRP2 gene expression in lymphocytes from patients with PD and controls. Results. Although initial analysis of the three variants rs892145, rs959117, and rs10888557 and a meta-analysis of rs892145 did not reveal any association between the selected variants and PD, we found an interaction between sex and genotype for rs892145, with a marked difference in the allele distribution of rs892145 between male and female patients. As compared to controls, the T allele was less common in female patients (odds ratio = 0.76, P = 0.04) and more common in male patients (odds ratio = 1.29, P = 0.04). No difference was found in PGLYRP2 gene expression between PD patients and controls (P = 0.38), nor between sexes (P = 0.07). Discussion. Overall, this genetic screening in Swedish PD patients does not support previous results demonstrating associations of PGLYRP variants with the risk of PD. Meta-analysis of rs892145 revealed pronounced heterogeneity between previously published studies which is likely to have influenced the results. Taken together, the genetic and gene expression analyses suggest a possible link between genetic variants in PGLYRP2 and sex differences in PD. Because of the limited sample size in our study, these results need to be verified in independent cohorts before concluding.http://dx.doi.org/10.1155/2023/6502727 |
| spellingShingle | Caroline Ran Karin Wirdefeldt Olof Sydow Per Svenningsson Rochellys Diaz Heijtz Sex Differences in the Allele Distribution of PGLYRP2 Variant rs892145 in Parkinson’s Disease Parkinson's Disease |
| title | Sex Differences in the Allele Distribution of PGLYRP2 Variant rs892145 in Parkinson’s Disease |
| title_full | Sex Differences in the Allele Distribution of PGLYRP2 Variant rs892145 in Parkinson’s Disease |
| title_fullStr | Sex Differences in the Allele Distribution of PGLYRP2 Variant rs892145 in Parkinson’s Disease |
| title_full_unstemmed | Sex Differences in the Allele Distribution of PGLYRP2 Variant rs892145 in Parkinson’s Disease |
| title_short | Sex Differences in the Allele Distribution of PGLYRP2 Variant rs892145 in Parkinson’s Disease |
| title_sort | sex differences in the allele distribution of pglyrp2 variant rs892145 in parkinson s disease |
| url | http://dx.doi.org/10.1155/2023/6502727 |
| work_keys_str_mv | AT carolineran sexdifferencesinthealleledistributionofpglyrp2variantrs892145inparkinsonsdisease AT karinwirdefeldt sexdifferencesinthealleledistributionofpglyrp2variantrs892145inparkinsonsdisease AT olofsydow sexdifferencesinthealleledistributionofpglyrp2variantrs892145inparkinsonsdisease AT persvenningsson sexdifferencesinthealleledistributionofpglyrp2variantrs892145inparkinsonsdisease AT rochellysdiazheijtz sexdifferencesinthealleledistributionofpglyrp2variantrs892145inparkinsonsdisease |