SNAP25 Gene Polymorphisms Protect Against Parkinson's Disease and Modulate Disease Severity in Patients

Cristina Agliardi, Franca Rosa Guerini, Milena Zanzottera, Giulio Riboldazzi, Roberta Zangaglia, Andrea Sturchio, Carlo Casali, Cherubino Di Lorenzo, Brigida Minafra, Raffaello Nemni, Mario Clerici

Research output: Contribution to journalArticle

Abstract

Parkinson's disease (PD) is a α-synucleinopathy in which intracellular aggregates of α-synuclein (α-syn) result in neurodegeneration and in the impairment of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex-mediated release of neurotransmitters. SNAP25 is a SNARE complex component: its concentration is increased in the cerebrospinal fluid of PD patients and this is related to the severity of cognitive and motor symptoms. Five SNAP25 single-nucleotide polymorphisms (SNPs) that modulate gene expression and were described to play a role in neurologic conditions (rs363050, rs363039, rs363043, rs3746544, and rs1051312) were analyzed in a cohort of 412 sporadic Italian PD patients and 1103 healthy controls (HC) in order to identify possible correlation with the disease. The SNAP25 rs1051312 C allele and CC genotype confer protection against PD onset, in particular in males (p = 0.003, OR(95%CI) = 0.67(0.51-0.88)) (pc = 0.008, OR(95%CI) = 0.28(0.10-0.70)). Co-segregation analyses revealed that the rs1051312 effect was reinforced when present within the rs363043 C-rs3746544 T-rs1051312 C haplotype (p = 3.3 × 10-4, OR = 0.47, 95%CI = 0.31-0.72), once again in males. Finally, rs363039 influenced age at onset (p = 0.02) and MMSE (Mini-Mental State Examination) scores (p = 0.01). The SNAP25 SNPs analyzed herein modulate gene expression at different levels as they are involved in binding miRNA and transcription factors; this suggests a possible synergistic effect of SNAP25 SNPs in the pathogenesis of PD. A replication in a larger and independent sample will help to further explore this hypothesis.

Original languageEnglish
Pages (from-to)4455-4463
Number of pages9
JournalMolecular Neurobiology
Volume56
Issue number6
DOIs
Publication statusPublished - Jun 2019

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Parkinson Disease
SNARE Proteins
Single Nucleotide Polymorphism
Genes
Synucleins
Gene Expression
Neurobehavioral Manifestations
MicroRNAs
Age of Onset
Haplotypes
Nervous System
Neurotransmitter Agents
Cerebrospinal Fluid
Transcription Factors
Alleles
Genotype

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SNAP25 Gene Polymorphisms Protect Against Parkinson's Disease and Modulate Disease Severity in Patients. / Agliardi, Cristina; Guerini, Franca Rosa; Zanzottera, Milena; Riboldazzi, Giulio; Zangaglia, Roberta; Sturchio, Andrea; Casali, Carlo; Di Lorenzo, Cherubino; Minafra, Brigida; Nemni, Raffaello; Clerici, Mario.

In: Molecular Neurobiology, Vol. 56, No. 6, 06.2019, p. 4455-4463.

Research output: Contribution to journalArticle

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abstract = "Parkinson's disease (PD) is a α-synucleinopathy in which intracellular aggregates of α-synuclein (α-syn) result in neurodegeneration and in the impairment of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex-mediated release of neurotransmitters. SNAP25 is a SNARE complex component: its concentration is increased in the cerebrospinal fluid of PD patients and this is related to the severity of cognitive and motor symptoms. Five SNAP25 single-nucleotide polymorphisms (SNPs) that modulate gene expression and were described to play a role in neurologic conditions (rs363050, rs363039, rs363043, rs3746544, and rs1051312) were analyzed in a cohort of 412 sporadic Italian PD patients and 1103 healthy controls (HC) in order to identify possible correlation with the disease. The SNAP25 rs1051312 C allele and CC genotype confer protection against PD onset, in particular in males (p = 0.003, OR(95{\%}CI) = 0.67(0.51-0.88)) (pc = 0.008, OR(95{\%}CI) = 0.28(0.10-0.70)). Co-segregation analyses revealed that the rs1051312 effect was reinforced when present within the rs363043 C-rs3746544 T-rs1051312 C haplotype (p = 3.3 × 10-4, OR = 0.47, 95{\%}CI = 0.31-0.72), once again in males. Finally, rs363039 influenced age at onset (p = 0.02) and MMSE (Mini-Mental State Examination) scores (p = 0.01). The SNAP25 SNPs analyzed herein modulate gene expression at different levels as they are involved in binding miRNA and transcription factors; this suggests a possible synergistic effect of SNAP25 SNPs in the pathogenesis of PD. A replication in a larger and independent sample will help to further explore this hypothesis.",
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T1 - SNAP25 Gene Polymorphisms Protect Against Parkinson's Disease and Modulate Disease Severity in Patients

AU - Agliardi, Cristina

AU - Guerini, Franca Rosa

AU - Zanzottera, Milena

AU - Riboldazzi, Giulio

AU - Zangaglia, Roberta

AU - Sturchio, Andrea

AU - Casali, Carlo

AU - Di Lorenzo, Cherubino

AU - Minafra, Brigida

AU - Nemni, Raffaello

AU - Clerici, Mario

PY - 2019/6

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N2 - Parkinson's disease (PD) is a α-synucleinopathy in which intracellular aggregates of α-synuclein (α-syn) result in neurodegeneration and in the impairment of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex-mediated release of neurotransmitters. SNAP25 is a SNARE complex component: its concentration is increased in the cerebrospinal fluid of PD patients and this is related to the severity of cognitive and motor symptoms. Five SNAP25 single-nucleotide polymorphisms (SNPs) that modulate gene expression and were described to play a role in neurologic conditions (rs363050, rs363039, rs363043, rs3746544, and rs1051312) were analyzed in a cohort of 412 sporadic Italian PD patients and 1103 healthy controls (HC) in order to identify possible correlation with the disease. The SNAP25 rs1051312 C allele and CC genotype confer protection against PD onset, in particular in males (p = 0.003, OR(95%CI) = 0.67(0.51-0.88)) (pc = 0.008, OR(95%CI) = 0.28(0.10-0.70)). Co-segregation analyses revealed that the rs1051312 effect was reinforced when present within the rs363043 C-rs3746544 T-rs1051312 C haplotype (p = 3.3 × 10-4, OR = 0.47, 95%CI = 0.31-0.72), once again in males. Finally, rs363039 influenced age at onset (p = 0.02) and MMSE (Mini-Mental State Examination) scores (p = 0.01). The SNAP25 SNPs analyzed herein modulate gene expression at different levels as they are involved in binding miRNA and transcription factors; this suggests a possible synergistic effect of SNAP25 SNPs in the pathogenesis of PD. A replication in a larger and independent sample will help to further explore this hypothesis.

AB - Parkinson's disease (PD) is a α-synucleinopathy in which intracellular aggregates of α-synuclein (α-syn) result in neurodegeneration and in the impairment of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex-mediated release of neurotransmitters. SNAP25 is a SNARE complex component: its concentration is increased in the cerebrospinal fluid of PD patients and this is related to the severity of cognitive and motor symptoms. Five SNAP25 single-nucleotide polymorphisms (SNPs) that modulate gene expression and were described to play a role in neurologic conditions (rs363050, rs363039, rs363043, rs3746544, and rs1051312) were analyzed in a cohort of 412 sporadic Italian PD patients and 1103 healthy controls (HC) in order to identify possible correlation with the disease. The SNAP25 rs1051312 C allele and CC genotype confer protection against PD onset, in particular in males (p = 0.003, OR(95%CI) = 0.67(0.51-0.88)) (pc = 0.008, OR(95%CI) = 0.28(0.10-0.70)). Co-segregation analyses revealed that the rs1051312 effect was reinforced when present within the rs363043 C-rs3746544 T-rs1051312 C haplotype (p = 3.3 × 10-4, OR = 0.47, 95%CI = 0.31-0.72), once again in males. Finally, rs363039 influenced age at onset (p = 0.02) and MMSE (Mini-Mental State Examination) scores (p = 0.01). The SNAP25 SNPs analyzed herein modulate gene expression at different levels as they are involved in binding miRNA and transcription factors; this suggests a possible synergistic effect of SNAP25 SNPs in the pathogenesis of PD. A replication in a larger and independent sample will help to further explore this hypothesis.

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DO - 10.1007/s12035-018-1386-0

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