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Association between the AKT1 single nucleotide polymorphism (rs2498786, rs2494752 and rs5811155) and microscopic
Lizhen Li1,2, Jinlan Rao1,3, Jingjing Lan1
1Department of Nephrology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Abstract:
Microscopic polyangiitis (MPA) is an autoimmune disease, characterized by ANCA in blood and necrotizing inflammation of small and medium-sized vessels, one of the three clinical phenotypes of ANCA-associated vasculitis (AAV). Autophagy has been confirmed to be involved in the pathogenesis of AAV. AKT1 is one of the autophagy-regulated proteins. Its single nucleotide polymorphisms (SNPs) are associated with multiple immune-related diseases, but there are rarely studies in AAV. The incidence rate of AAV has a notable geographic difference, and MPA is predominant in China. The aim of this study was to investigate the association between AKT1 SNP and MPA risk. Genotypes of 8 loci in AKT1 were evaluated by multiplex polymerase chain reaction (PCR) and high-throughput sequencing in 416 people, including 208 MPA patients and 208 healthy volunteers from Guangxi in China. Additionally, data of 387 healthy volunteers from China were obtained from the 1000Genomes Project on public database. Differences were observed between the loci (rs2498786, rs2494752, and rs5811155) genotypes in AKT1 and MPA risk (P = 7.0 × 10-4, P = 3.0 × 10-4, and P = 5.9 × 10-5, respectively). A negative association was detected in the Dominant model (P = 1.2 × 10-3, P = 2.0 × 10-4 and P = 3.6 × 10-5, respectively). A haplotype (G-G-T) was associated with MPA risk negatively (P = 7.0 × 10-4). This study suggests that alleles (rs2498786 G, rs2494752 G and rs5811155 insT) are protective factors for MPA and alleles (rs2494752 G and rs5811155 insT) for MPO-ANCA in patients with MPA. There is a haplotype (G-G-T), which is a protective factor for MPA. It suggests that the role of AKT1 in MPA/AAV needs further study to provide more intervention targets for MPA/AAV.
Insights
Certain AKT1 gene variations act as protective factors against microscopic polyangiitis (MPA), an autoimmune disease. This research identifies specific alleles and a haplotype that may reduce MPA risk, suggesting AKT1 as a potential therapeutic target.
Area of Science:
- Immunology
- Genetics
- Autoimmune Diseases
Background:
- Microscopic polyangiitis (MPA) is an autoimmune disease characterized by ANCA and small vessel inflammation, a phenotype of ANCA-associated vasculitis (AAV).
- Autophagy plays a role in AAV pathogenesis, and AKT1 is an autophagy-regulated protein implicated in immune-related diseases.
- Geographic variations exist in AAV incidence, with MPA being more prevalent in China, highlighting the need for population-specific genetic studies.
Purpose of the Study:
- To investigate the association between single nucleotide polymorphisms (SNPs) in the AKT1 gene and the risk of developing MPA.
- To explore the potential protective effects of specific AKT1 alleles and haplotypes against MPA in a Chinese population.
Main Methods:
- Genotyping of 8 loci in the AKT1 gene was performed using multiplex polymerase chain reaction (PCR) and high-throughput sequencing.
- A cohort of 416 individuals (208 MPA patients and 208 healthy controls) from Guangxi, China, was analyzed.
- Publicly available data from 387 healthy Chinese volunteers from the 1000 Genomes Project were included for comparison.
Main Results:
- Significant associations were found between specific AKT1 genotypes (rs2498786, rs2494752, and rs5811155) and MPA risk.
- A negative association was observed in the Dominant model for these loci, indicating a protective effect.
- A specific haplotype (G-G-T) in AKT1 was found to be negatively associated with MPA risk, suggesting a protective role.
Conclusions:
- Certain AKT1 alleles (rs2498786 G, rs2494752 G, and rs5811155 insT) appear to be protective factors against MPA.
- The G-G-T haplotype in AKT1 is identified as a protective factor for MPA.
- These findings suggest that AKT1 warrants further investigation for its role in MPA/AAV pathogenesis and as a potential target for therapeutic interventions.
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