Glutamine and allergic rhinitis: A bidirectional two-sample Mendelian randomization study

Glutamine (Gln) has been implicated as a potential protective factor against allergic rhinitis (AR), with supplementation studies suggesting improved patient prognosis. However, the precise relationship between circulating Gln levels and AR risk remains unclear. To address this, we employed bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal association between Gln and AR. Genome-wide association study (GWAS) summary statistics for AR (FinnGen dataset finn-b-ALLERGY_RHINITIS; 217,914 samples; 16,380,461 single nucleotide polymorphisms [SNPs]) and circulating Gln levels (met-d-Gln; 114,750 samples; 12,321,875 SNPs) were obtained from the Integrative Epidemiology Unit Open GWAS database. MR analyses were performed, primarily using the inverse variance weighted (IVW; fixed-effects) method. Sensitivity analyses included the weighted median, simple median, MR-Egger, and maximum likelihood methods. Robustness of the MR findings was further assessed via heterogeneity tests, horizontal pleiotropy evaluation (MR-Egger intercept test), and leave-one-out (LOO) analysis. Additionally, phenotypic association scanning was conducted for both AR and Gln. Forward MR (Gln→AR) revealed a significant negative causal association, identifying Gln as a protective factor for AR (IVW OR < 1; P < .05). Reverse MR (AR→Gln) showed no causal effect (P > .05). Sensitivity analyses confirmed reliability: no significant heterogeneity (Q_P > .05) or horizontal pleiotropy (P > .05) was detected in either direction, and LOO analysis supported result stability. Phenotypic scanning corroborated Gln as a protective factor against AR (OR = 0.874, 95% CI = 0.77047-0.99093, P = .036). Our study suggests that Gln is a protective factor against AR and that AR is not causally associated with Gln.