Expressive

rs1115363 (IFITM3P1-MIR1269A): Nicotine Metabolism

Key takeaways

  • Genetics explains about 33% of between-person differences in cotinine processing, with a roughly three-times stronger effect in African Americans (55%) than in Japanese Americans (19%).
  • A genome-wide scan of 2,239 smokers across five racial and ethnic groups found over 1,200 variants linked to how the body chemically processes nicotine.
  • rs1115363 sits near IFITM3P1 and MIR1269A, two non-coding genomic elements.
  • Specific data for rs1115363 are not reported in the available study text; its role in nicotine metabolism is preliminary.

Key takeaways

  • Genetics explains about 33% of between-person differences in cotinine processing, with a roughly three-times stronger effect in African Americans (55%) than in Japanese Americans (19%).
  • A genome-wide scan of 2,239 smokers across five racial and ethnic groups found over 1,200 variants linked to how the body chemically processes nicotine.
  • rs1115363 sits near IFITM3P1 (interferon-induced transmembrane protein 3 pseudogene 1) and MIR1269A (a microRNA regulatory gene), both non-coding genomic elements.
  • Specific data for rs1115363 are not reported in the available study text; its role in nicotine metabolism is preliminary.

What the research says A GWAS (genome-wide association study, a method that scans millions of variants simultaneously) by Patel et al. (2015) analyzed 11,892,802 variants in 2,239 smokers from five racial and ethnic groups in the Multiethnic Cohort Study to identify genetic predictors of nicotine and cotinine glucuronidation (glucuronidation is a chemical process that attaches a molecular tag to nicotine and cotinine, making them easier to excrete in urine). The study found 1,241 variants at genome-wide significance (p<5x10-8) for cotinine glucuronidation and 490 at the same threshold for nicotine glucuronidation, with the vast majority clustering near UGT2B10, an enzyme gene on chromosome 4q13. The available study text does not name rs1115363 individually or report effect-size statistics specific to this locus.

Reported associations

  • Cotinine glucuronidation: A GWAS in 2,239 multi-ethnic smokers (European Americans n=437, African Americans n=364, Latinos n=453, Japanese Americans n=674, Native Hawaiians n=311) identified 1,241 genome-wide significant variants; 15 independent variants together explained 33.2% of between-person variation, ranging from 55% in African Americans to 19% in Japanese Americans. Whether rs1115363 is among these variants is not stated in the available study text.
  • Nicotine glucuronidation: 490 variants in the same GWAS also reached genome-wide significance (p<5x10-8) for this related trait; the specific contribution of this locus is not described in the available study text.

Evidence quality The underlying GWAS enrolled 2,239 smokers from five racial and ethnic groups and applied a stringent genome-wide significance threshold (p<5x10-8), the standard cutoff when millions of variants are tested simultaneously to control for false positives. Urinary concentrations of nicotine and six metabolites were measured directly, providing objective phenotypic data rather than self-reported estimates. The study identified 15 independent genome-wide significant variants for cotinine glucuronidation; the single strongest association was rs115765562 (p=1.60x10-155), and the top variant for nicotine glucuronidation was rs116224959 (p=2.56x10-43). However, the available study text does not report a p-value, odds ratio, or replication result for rs1115363 specifically; the evidence for this variant is limited to the broader GWAS context and should be treated as preliminary.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What does the IFITM3P1 gene do?

IFITM3P1 is a pseudogene, meaning it is a non-functional genomic copy of the IFITM3 gene (interferon-induced transmembrane protein 3, which helps cells resist certain viral infections). MIR1269A, also near this locus, encodes a small microRNA molecule involved in regulating other genes. The specific role of this region in nicotine metabolism is not described in the available study.

Is rs1115363 linked to smoking behavior or lung cancer?

The study providing context for rs1115363 examined how people chemically process nicotine and cotinine, not directly smoking behavior or lung cancer. The researchers noted that genetic variation in nicotine-processing enzymes is unlikely to contribute directly to lung cancer risk. Specific findings for rs1115363 are not reported in the available study text.

What is nicotine glucuronidation?

Glucuronidation is a chemical process in which the body attaches a glucuronic acid tag to a substance to make it more water-soluble and easier to excrete in urine. Applied to nicotine and its main breakdown product cotinine, this process is regulated largely by the UGT2B10 enzyme, and genetic differences in this enzyme explain a substantial share of the variation in how fast different people clear nicotine.

Does genetics affect nicotine processing differently across ethnic groups?

Yes. A genome-wide study found that 15 genetic variants together explained about 55% of between-person variation in cotinine glucuronidation in African Americans, compared to about 19% in Japanese Americans, indicating the genetic architecture of this trait differs substantially across populations.