Investigating the prevalence of the G2019S mutation in Parkinson's disease among a Libyan population

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder influenced by both environmental and genetic risk factors. This study investigates the prevalence of the LRRK2 G2019S mutation in a Libyan population of 140 PD patients and 58 controls. Genetic analysis of blood samples revealed that 19.5% of PD patients carry the G2019S mutation, indicating a genetic association with the disease. The study highlights the G2019S mutation as a potential genetic risk factor for PD in Libya and emphasizes the importance of genetic screening for better understanding and management of the disease.

Plain language summary

The G2019S mutation in the LRRK2 gene is a genetic alteration linked to Parkinson's disease (PD), and this study aimed to explore its prevalence among individuals with PD in Libya. We focused on how common this mutation is in the Libyan PD population, hypothesizing that it would be present in a significant number of patients. Understanding the prevalence of this mutation is crucial for gaining insights into the genetic factors contributing to PD. This research is important as it addresses a significant gap in knowledge about PD in Libya, a condition that affects millions worldwide. We conducted a study involving 140 patients diagnosed with PD and a control group of healthy individuals. Our findings revealed that approximately 19.5% of the PD patients had the G2019S mutation. These results provide the first insights into the genetic landscape of PD in Libya, highlighting the need for further research to inform better diagnostic and treatment options for patients. The key aim is that understanding the role of genetic factors, such as the G2019S mutation in the LRRK2 gene, is vital for enhancing our knowledge of PD and improving patient outcomes. Continued research in this area is essential to develop more effective diagnostic tools and targeted treatments for individuals affected by this condition.

To the editors of the Journal of Parkinson's Disease,

We would like to report the results of our recent investigation into the genetic risk factors associated with Parkinson's disease (PD) in Libya, particularly examining the prevalence of the Leucine-Rich Repeat Kinase 2 (LRRK2) G2019S mutation within the Libyan population. We utilized a consecutive sampling approach to enroll all PD patients who were diagnosed within a specific timeframe. The study comprised 140 PD patients and 58 healthy controls. Each PD patient underwent evaluation by a neurologist to confirm their diagnosis. The severity of PD was assessed using the Hoehn and Yahr (H&Y) scale, which classifies the disease based on the severity of motor symptoms. Healthy controls were recruited from the general population and were subjected to a clinical interview to confirm the absence of any neurological disorders, including PD and other movement disorders, as well as any significant family history of neurodegenerative diseases. Subsequently, we performed Sanger sequencing to examine the prevalence of G2019S mutations and other variants in the LRRK2 gene.

Of the 140 recruited PD patients, 12 samples were excluded due to falling below detection limits. Similarly, 7 samples from the control group were also excluded from the analysis. The mean ages of the PD patients and healthy controls were 66.75 years and 43.1 years, respectively (see Supplemental Table 1 for more details). Our study found that 19.5% of the PD patients carry the G2019S mutation (Table 1), highlighting a notable genetic link to the disease. Additionally, the G2019S variant was identified in four control individuals (7.8%) (Table 1), which aligns with other recent findings that detected the same mutation in control subjects.^1,2 Targeted screening for other recognized mutations in the LRRK2 gene within specific exons that have been documented in the literature as linked to PD was also conducted. The specific mutations included: R793 M (arginine to methionine at position 793), L1114L (no change, leucine to leucine at position 1114), R1441C (arginine to cysteine at position 1441), R1441G (arginine to glycine at position 1441), Y1699C (tyrosine to cysteine at position 1699), M1869 T (methionine to threonine at position 1869), and I2020 T (isoleucine to threonine at position 2020). Notably, none of these mutations were detected in our screened cohort, meaning that the G2019S mutation (where glycine is replaced by serine at the position 2019) is the commonest variant among Libyans with PD. This indicates that G2019S carriers may be at increased risk for developing PD, although not all may exhibit clinical symptoms, suggesting incomplete penetrance influenced by environmental and genetic factors. ³

Table 1.

Demographics G2019S mutation carriers and non-carriers.

	PD G2019S LRRK2 carriers			PD G2019S LRRK2 non-carriers	p (PD carriers vs. PD non-carriers)	Control G2019S LRRK2 carriers			p (cases vs. controls)
	All	Homozygous	heterozygous	All		All	Homozygous	Heterozygous
Sample size	25 (19.5%)	3 (12%)	22 (88%)	103 (80.5%)		4 (7.8%)	-	4 (100%)	0.09
Sex ratio (M:F)	1.7 (16:9)	2 (2:1)	1.75 (14:8)	1.8 (67:36)	1.0	1 (2:2)	-	1 (2:2)
Mean age (SD)	64.3 (10.5)	64.6 (6.4)	64.3 (11)	67.1 (10)	0.3	50.7 (14.2)	-	50.75

*

M: male; F: female; SD: standard deviation

PD is a progressive neurodegenerative disorder characterized by various motor and non-motor symptoms that significantly impact patients’ quality of life. In the last fifteen years, genetic research in PD has identified several monogenic forms and various genetic risk factors associated with the disease. Monogenic forms, caused by single mutations in inherited genes, are relatively rare, accounting for about 30% of familial cases and 3% to 5% of sporadic cases. ⁴ The G2019S mutation in the LRRK2 gene is one of the most common genetic factors associated with both familial and sporadic PD, ⁵ particularly prevalent in North African populations. ⁶ The LRRK2 gene, located on chromosome 12, encodes a protein involved in critical cellular processes, and the G2019S mutation leads to increased kinase activity, contributing to neurodegeneration. ³

Studies have shown varying prevalence rates of the G2019S mutation in North African countries, with notable frequencies in Tunisia (33.6%), ⁷ Algeria (35.9%),^8,9 and Morocco (41%).^10,11 In Egypt, the mutation's prevalence among PD patients has been reported at 4.4%. ¹ These findings highlight the importance of understanding genetic factors in PD and the need for targeted screening in populations with higher mutation rates. Our research offers new perspectives on the genetic underpinnings of PD in Libya, emphasizing the LRRK2 G2019S mutation as a possible genetic risk factor. These results are important as they indicate that this mutation could be a key contributor to the development of PD in Libyan population, which has not been thoroughly studied within the North African context.

Our findings emphasize the importance of genetic screening in understanding PD risk factors in underrepresented populations and highlight the need for larger studies to evaluate the relationship between LRRK2 mutations and PD in Libya. The study further contributes to understanding genetic risk factors for PD in North Africa, particularly regarding the G2019S variant, and underscores the necessity for localized genetic studies to inform public health initiatives and genetic counseling. It also lays the groundwork for future therapeutic developments, such as LRRK2 inhibitors, and personalized medicine approaches. However, the study's limitations include a small sample size, very small control participant numbers, and lack of age matching, which may affect the robustness of the findings. Future research with larger, age-matched cohorts is needed to validate these results and enhance understanding of the genetic landscape of PD in Libya. Establishing a clearer understanding of the G2019S mutation's prevalence can enhance clinical approaches and support the development of targeted therapeutic interventions that address the unique genetic landscape of the region.

Supplemental Material

sj-docx-1-pkn-10.1177_1877718X251324407 - Supplemental material for Investigating the prevalence of the G2019S mutation in Parkinson's disease among a Libyan population

Supplemental material, sj-docx-1-pkn-10.1177_1877718X251324407 for Investigating the prevalence of the G2019S mutation in Parkinson's disease among a Libyan population by Nuri H Awayn, Sara A Hashish, Sultan A Salem, Sulieman Abod, Sana M Elgahmasi, Khalid Ouararhni, Houari Abdesselem, Ilham Y Abdi and Omar A El-Agnaf in Journal of Parkinson's Disease