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AKT1 but not AKT2 single nucleotide polymorphisms are associated with the risk of microscopic polyangiitis

genetics
allergy-and-clinical-immunology
immunology
rheumatology
medical-genetics

Abstract

Background: Microscopic polyangiitis (MPA), a severe ANCA-associated vasculitis, has been linked to genetic factors such as single-nucleotide polymorphisms (SNPs). While AKT1 and AKT2 are known to regulate immune and metabolic pathways, their distinct roles in MPA susceptibility remain unclear. This study investigates the association between AKT1 and AKT2 SNPs and MPA risk in a Chinese population.

Methods: A case–control study was conducted involving 202 MPA patients and 596 healthy controls. Seven SNPs (four in AKT1 and three in AKT2) were selected based on allele frequency differences from the 1000 Genomes Project. Genotyping was performed using whole-genome sequencing, and logistic regression was used for association analysis. Subgroup analyses examined P-ANCA positivity and gender interactions. Haplotype and SNP–SNP interaction analyses were also conducted to explore genetic relationships.

Results: Three AKT1 SNPs—rs2498786 G (OR = 0.62, P = 0.001), rs2498801 T (OR = 0.71, P = 0.033), and rs1130233 C (OR = 0.58, P = 0.0004)—were significantly associated with reduced MPA risk. No significant associations were found for AKT2 SNPs. Haplotype analysis identified two protective AKT1 haplotypes (G-T-C-T and C-C-C-A, P < 0.01). SNP–SNP interaction analysis revealed high-risk genotype combinations, such as rs2498786 CC + rs1130233 TT. Subgroup analysis linked AKT1 SNPs to serum P-ANCA positivity, and rs2498786 showed a gender-specific effect (P-interaction = 0.007).

Conclusions: AKT1, but not AKT2, SNPs are associated with MPA susceptibility, likely due to AKT1’s role in immune regulation and inflammation. These findings highlight AKT1 as a potential genetic marker for MPA risk and underscore the need for functional studies to further elucidate its mechanistic pathways.

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