MRPL4 – Allergic Rhinitis

MRPL4, encoding a mitochondrial ribosomal protein, has been implicated in the susceptibility to allergic rhinitis (AR), a chronic inflammatory disease of the nasal mucosa. In two independent studies, significant associations were observed between MRPL4 polymorphisms and AR risk in East Asian populations. The first study used a genome‑wide association approach in a large Singapore Chinese cohort where the MRPL4 locus (rs8111930) was identified as a candidate, showing a protective odds ratio (OR = 0.69) and replication in an independent cohort (PMID:21625490). The second study, focusing on Han Chinese subjects, identified MRPL4 SNP rs11668618 as significantly more frequent in AR patients compared to controls, underscoring its potential role in disease susceptibility (PMID:23472126). Together, these data from multi‑patient genetic association studies highlight a statistically supported link between MRPL4 and AR, although they do not document familial segregation or de novo mutations.

In terms of genetic evidence, the studies employed robust case‑control designs with large sample sizes and replication cohorts, thereby strengthening the association signal. The evidence is bolstered by statistically significant p‑values and effect sizes that are consistently reported across independent investigations. Despite strong genetic association evidence, no familial segregation data or detailed variant function, such as a confirmed HGVS‑coded variant among AR patients, was provided in the available literature. This impedes the ability to assign a definitive variant-level causality, resulting in the inclusion of genetic evidence as only moderate at this stage.

Regarding the mode of inheritance, AR is recognized as a complex, multifactorial trait rather than following a classic Mendelian pattern. The association of MRPL4 with AR reflects a genetic predisposition that, in combination with environmental factors, contributes to disease risk. As such, the inheritance pattern for AR in relation to MRPL4 is best described as complex, diverging from conventional autosomal dominant or autosomal recessive models. Additionally, no information was provided on extended familial segregation of MRPL4 variants, and the available studies did not assess the transmission of these alleles in familial contexts.

The experimental functional evidence for the role of MRPL4 in AR is limited. While MRPL4 is a key component of mitochondrial ribosomes and may influence cellular stress responses, the studies did not include functional assays, expression studies, animal models, or rescue experiments that directly link MRPL4 dysfunction to an AR phenotype. Consequently, the lack of functional validation leaves a gap in our overall interpretation of the pathogenic mechanism and limits its immediate translational application in diagnostic contexts.

Integrating the genetic and experimental data, the current body of evidence supports a moderate gene‑disease association between MRPL4 and allergic rhinitis. Although two large-scale association studies provide statistically significant support, the absence of mechanistic, functional studies and familial segregation data tempers the overall confidence in this association. The findings suggest that MRPL4 should be considered a candidate gene for AR risk, warranting further evaluation in diverse populations and through functional assays.

Key take‑home: MRPL4 represents a promising candidate gene for allergic rhinitis, with replicated genetic association evidence, yet further functional characterization is essential for its clinical and commercial utility in diagnostic decision‑making.

References

• PloS One • 2011 • Genome-wide association study for atopy and allergic rhinitis in a Singapore Chinese population PMID:21625490
• PloS One • 2013 • The association between polymorphisms in the MRPL4 and TNF-α genes and susceptibility to allergic rhinitis PMID:23472126

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