Functional variant rs17525453 within RAB35 gene promoter is possibly associated with increased risk of Parkinson's disease in Taiwanese population.

Hung Li Wang; Tu Hsueh Yeh; Ying Zu Huang; Yi Hsin Weng; Rou Shayn Chen; Chin Song Lu; Kuo Chen Wei; Yu Chuan Liu; Ying Ling Chen; Chao Lang Chen; Yu Jie Chen; Yan Wei Lin; Chia Chen Hsu; Chi Han Chiu; Ching Chi Chiu

doi:10.1016/j.neurobiolaging.2021.06.011

Functional variant rs17525453 within RAB35 gene promoter is possibly associated with increased risk of Parkinson's disease in Taiwanese population.

Hung Li Wang, Tu Hsueh Yeh, Ying Zu Huang, Yi Hsin Weng, Rou Shayn Chen, Chin Song Lu, Kuo Chen Wei, Yu Chuan Liu, Ying Ling Chen, Chao Lang Chen, Yu Jie Chen, Yan Wei Lin, Chia Chen Hsu, Chi Han Chiu, Ching Chi Chiu

Research output: Contribution to journal › Article › peer-review

Abstract

Our previous study suggests that upregulated RAB35 is implicated in etiology of Parkinson's disease (PD). We hypothesized that upregulated RAB35 results from single nucleotide polymorphisms (SNPs) in RAB35 gene promoter. We identified SNPs within RAB35 gene promoter by analyzing DNA samples of discovery cohort and validation cohort. SNP rs17525453 within RAB35 gene promoter (T>C at position of -66) was significantly associated with idiopathic PD patients. Compared to normal controls, sporadic PD patients had higher C allele frequency. CC and CT genotype significantly increased risk of PD compared with TT genotype. SNP rs17525453 within RAB35 gene promoter leads to formation of transcription factor TFII-I binding site. Results of EMSA and supershift assay indicated that TFII-I binds to rs17525453 sequence of RAB35 gene promoter. Luciferase reporter assays showed that rs17525453 variant of RAB35 gene promoter possesses an augmented transcriptional activity. Our results suggest that functional variant rs17525453 within RAB35 gene promoter is likely to enhance transcriptional activity and upregulate RAB35 protein, which could lead to increased risk of PD in Taiwanese population.

Original language	English
Pages (from-to)	189-196
Number of pages	8
Journal	Neurobiology of Aging
Volume	107
DOIs	https://doi.org/10.1016/j.neurobiolaging.2021.06.011
Publication status	Published - Nov 2021

Keywords

Parkinson's disease
promoter
RAB35
rs17525453
SNP
TFII-I
Transcriptional activity

ASJC Scopus subject areas

General Neuroscience
Ageing
Developmental Biology
Clinical Neurology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2021.06.011

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Wang, H. L., Yeh, T. H., Huang, Y. Z., Weng, Y. H., Chen, R. S., Lu, C. S., Wei, K. C., Liu, Y. C., Chen, Y. L., Chen, C. L., Chen, Y. J., Lin, Y. W., Hsu, C. C., Chiu, C. H., & Chiu, C. C. (2021). Functional variant rs17525453 within RAB35 gene promoter is possibly associated with increased risk of Parkinson's disease in Taiwanese population. Neurobiology of Aging, 107, 189-196. https://doi.org/10.1016/j.neurobiolaging.2021.06.011

Wang, HL, Yeh, TH, Huang, YZ, Weng, YH, Chen, RS, Lu, CS, Wei, KC, Liu, YC, Chen, YL, Chen, CL, Chen, YJ, Lin, YW, Hsu, CC, Chiu, CH & Chiu, CC 2021, 'Functional variant rs17525453 within RAB35 gene promoter is possibly associated with increased risk of Parkinson's disease in Taiwanese population.', Neurobiology of Aging, vol. 107, pp. 189-196. https://doi.org/10.1016/j.neurobiolaging.2021.06.011

@article{bfd884318117410993a2f18162e9805a,

title = "Functional variant rs17525453 within RAB35 gene promoter is possibly associated with increased risk of Parkinson's disease in Taiwanese population.",

abstract = "Our previous study suggests that upregulated RAB35 is implicated in etiology of Parkinson's disease (PD). We hypothesized that upregulated RAB35 results from single nucleotide polymorphisms (SNPs) in RAB35 gene promoter. We identified SNPs within RAB35 gene promoter by analyzing DNA samples of discovery cohort and validation cohort. SNP rs17525453 within RAB35 gene promoter (T>C at position of -66) was significantly associated with idiopathic PD patients. Compared to normal controls, sporadic PD patients had higher C allele frequency. CC and CT genotype significantly increased risk of PD compared with TT genotype. SNP rs17525453 within RAB35 gene promoter leads to formation of transcription factor TFII-I binding site. Results of EMSA and supershift assay indicated that TFII-I binds to rs17525453 sequence of RAB35 gene promoter. Luciferase reporter assays showed that rs17525453 variant of RAB35 gene promoter possesses an augmented transcriptional activity. Our results suggest that functional variant rs17525453 within RAB35 gene promoter is likely to enhance transcriptional activity and upregulate RAB35 protein, which could lead to increased risk of PD in Taiwanese population.",

keywords = "Parkinson's disease, promoter, RAB35, rs17525453, SNP, TFII-I, Transcriptional activity",

author = "Wang, {Hung Li} and Yeh, {Tu Hsueh} and Huang, {Ying Zu} and Weng, {Yi Hsin} and Chen, {Rou Shayn} and Lu, {Chin Song} and Wei, {Kuo Chen} and Liu, {Yu Chuan} and Chen, {Ying Ling} and Chen, {Chao Lang} and Chen, {Yu Jie} and Lin, {Yan Wei} and Hsu, {Chia Chen} and Chiu, {Chi Han} and Chiu, {Ching Chi}",

note = "Funding Information: This investigation was funded by the Ministry of Science and Technology, Taiwan (MOST107-2320-B-182-036-MY3 to HL Wang; MOST109-2314-B-182A-072-MY3 to CC Chiu), Chang Gung Memorial Hospital , Taiwan ( CMRPD1H0283 to HL Wang; CMRPG3K0951-2 and CMRPG3J0761-3 to CC Chiu) and Healthy Aging Research Center ( EMRPD1H0551 , EMRPD1H0381 , EMRPD1K0481 and EMRPD1K0361 ), Chang Gung University , Taiwan. Funding Information: This investigation was funded by the Ministry of Science and Technology, Taiwan (MOST107-2320-B-182-036-MY3 to HL Wang; MOST109-2314-B-182A-072-MY3 to CC Chiu), Chang Gung Memorial Hospital, Taiwan (CMRPD1H0283 to HL Wang; CMRPG3K0951-2 and CMRPG3J0761-3 to CC Chiu) and Healthy Aging Research Center (EMRPD1H0551, EMRPD1H0381, EMRPD1K0481 and EMRPD1K0361), Chang Gung University, Taiwan. Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = nov,

doi = "10.1016/j.neurobiolaging.2021.06.011",

language = "English",

volume = "107",

pages = "189--196",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Functional variant rs17525453 within RAB35 gene promoter is possibly associated with increased risk of Parkinson's disease in Taiwanese population.

AU - Wang, Hung Li

AU - Yeh, Tu Hsueh

AU - Huang, Ying Zu

AU - Weng, Yi Hsin

AU - Chen, Rou Shayn

AU - Lu, Chin Song

AU - Wei, Kuo Chen

AU - Liu, Yu Chuan

AU - Chen, Ying Ling

AU - Chen, Chao Lang

AU - Chen, Yu Jie

AU - Lin, Yan Wei

AU - Hsu, Chia Chen

AU - Chiu, Chi Han

AU - Chiu, Ching Chi

N1 - Funding Information: This investigation was funded by the Ministry of Science and Technology, Taiwan (MOST107-2320-B-182-036-MY3 to HL Wang; MOST109-2314-B-182A-072-MY3 to CC Chiu), Chang Gung Memorial Hospital , Taiwan ( CMRPD1H0283 to HL Wang; CMRPG3K0951-2 and CMRPG3J0761-3 to CC Chiu) and Healthy Aging Research Center ( EMRPD1H0551 , EMRPD1H0381 , EMRPD1K0481 and EMRPD1K0361 ), Chang Gung University , Taiwan. Funding Information: This investigation was funded by the Ministry of Science and Technology, Taiwan (MOST107-2320-B-182-036-MY3 to HL Wang; MOST109-2314-B-182A-072-MY3 to CC Chiu), Chang Gung Memorial Hospital, Taiwan (CMRPD1H0283 to HL Wang; CMRPG3K0951-2 and CMRPG3J0761-3 to CC Chiu) and Healthy Aging Research Center (EMRPD1H0551, EMRPD1H0381, EMRPD1K0481 and EMRPD1K0361), Chang Gung University, Taiwan. Publisher Copyright: © 2021

PY - 2021/11

Y1 - 2021/11

N2 - Our previous study suggests that upregulated RAB35 is implicated in etiology of Parkinson's disease (PD). We hypothesized that upregulated RAB35 results from single nucleotide polymorphisms (SNPs) in RAB35 gene promoter. We identified SNPs within RAB35 gene promoter by analyzing DNA samples of discovery cohort and validation cohort. SNP rs17525453 within RAB35 gene promoter (T>C at position of -66) was significantly associated with idiopathic PD patients. Compared to normal controls, sporadic PD patients had higher C allele frequency. CC and CT genotype significantly increased risk of PD compared with TT genotype. SNP rs17525453 within RAB35 gene promoter leads to formation of transcription factor TFII-I binding site. Results of EMSA and supershift assay indicated that TFII-I binds to rs17525453 sequence of RAB35 gene promoter. Luciferase reporter assays showed that rs17525453 variant of RAB35 gene promoter possesses an augmented transcriptional activity. Our results suggest that functional variant rs17525453 within RAB35 gene promoter is likely to enhance transcriptional activity and upregulate RAB35 protein, which could lead to increased risk of PD in Taiwanese population.

AB - Our previous study suggests that upregulated RAB35 is implicated in etiology of Parkinson's disease (PD). We hypothesized that upregulated RAB35 results from single nucleotide polymorphisms (SNPs) in RAB35 gene promoter. We identified SNPs within RAB35 gene promoter by analyzing DNA samples of discovery cohort and validation cohort. SNP rs17525453 within RAB35 gene promoter (T>C at position of -66) was significantly associated with idiopathic PD patients. Compared to normal controls, sporadic PD patients had higher C allele frequency. CC and CT genotype significantly increased risk of PD compared with TT genotype. SNP rs17525453 within RAB35 gene promoter leads to formation of transcription factor TFII-I binding site. Results of EMSA and supershift assay indicated that TFII-I binds to rs17525453 sequence of RAB35 gene promoter. Luciferase reporter assays showed that rs17525453 variant of RAB35 gene promoter possesses an augmented transcriptional activity. Our results suggest that functional variant rs17525453 within RAB35 gene promoter is likely to enhance transcriptional activity and upregulate RAB35 protein, which could lead to increased risk of PD in Taiwanese population.

KW - Parkinson's disease

KW - promoter

KW - RAB35

KW - rs17525453

KW - SNP

KW - TFII-I

KW - Transcriptional activity

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U2 - 10.1016/j.neurobiolaging.2021.06.011

DO - 10.1016/j.neurobiolaging.2021.06.011

M3 - Article

C2 - 34275689

AN - SCOPUS:85110507731

SN - 0197-4580

VL - 107

SP - 189

EP - 196

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

Functional variant rs17525453 within RAB35 gene promoter is possibly associated with increased risk of Parkinson's disease in Taiwanese population.

Abstract

Keywords

ASJC Scopus subject areas

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