rs12141575 (IL12RB2): Immune Signaling and Inflammation

Key takeaways

• This variant lies in the genomic region between DNAJB6P4, a pseudogene, and IL12RB2 (interleukin-12 receptor beta-2), the gene encoding one of two receptor chains needed for IL-12 immune signaling
• The IL-12 pathway is relevant to inflammatory arthritis: the related gene IL12B is a confirmed genome-wide significant risk locus for ankylosing spondylitis (AS), a chronic inflammatory arthritis of the spine
• A large immune-focused genotyping study of 10,619 AS cases and 15,145 controls covering this genomic neighborhood identified 13 new risk loci
• Host genetic variants in immune-related regions such as this one have been associated with gut microbiome composition in a sample of 1,514 individuals
• The provided literature does not report a named, quantified effect size for rs12141575 directly

What the research says A genome-wide analysis of host genetics and gut microbiome composition in 1,514 individuals identified 9 genetic loci associated with microbial taxonomies and 33 with microbial pathways at genome-wide significance (P < 5 x 10^-8), plus 32 suggestive loci in regions of innate and adaptive immunity that include this locus's genomic neighborhood PMID 28086870. A dense Immunochip case-control study of ankylosing spondylitis (a chronic inflammatory arthritis primarily of the spine and pelvis, affecting roughly 0.55% of Europeans and about 0.23% of Chinese populations) in 10,619 cases and 15,145 controls of multiple ancestries confirmed IL12B as a risk locus for this condition and identified 13 new genome-wide significant loci, using a platform designed to densely cover immune-related regions including the IL-12 receptor gene neighborhood PMID 24162737.

Reported associations

• Gut microbiome composition (immune-region context): In a study of 1,514 individuals, genetic variants in immune-related genomic regions were found to influence microbial species and metabolic pathway abundances, with 9 loci reaching genome-wide significance for microbial taxa and 33 for pathways, plus 32 immune-region loci at the suggestive threshold; no specific effect size is reported for this locus individually PMID 28086870
• Ankylosing spondylitis susceptibility (IL-12 pathway context): The IL-12 signaling pathway is implicated in AS susceptibility; the related gene IL12B (encoding the IL-12 p40 subunit) is confirmed at genome-wide significance in a study of over 25,000 individuals, and the Immunochip platform densely genotypes the broader IL-12 receptor gene neighborhood as part of immune-disease research PMID 24162737

Evidence quality The two provided studies supply pathway-level and regional context for this variant but do not explicitly quantify an association for rs12141575 itself. The gut microbiome study (n=1,514) used metagenomic sequencing with a genome-wide plus targeted design, reporting 32 immune-region loci at the suggestive level without naming this specific variant in the provided text PMID 28086870. The AS study (n=10,619 cases, 15,145 controls) used the Immunochip with minimal population stratification (genomic inflation factor lambda=1.047) and identified 25 genome-wide significant loci and 6 suggestive loci (P < 5 x 10^-7) across European, East Asian, and Latin American cohorts, but does not name rs12141575 specifically in the provided excerpt PMID 24162737. Evidence for this variant as a risk factor for any specific phenotype should be considered indirect and preliminary based on the available literature.

Lifestyle considerations No lifestyle considerations on file for this variant.