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In genome‐wide association studies (GWAS), genetic variants in OCTN1 have been associated with blood cell counts (monocytes, neutrophils, white blood cells, and granulocytes) [86], blood metabolite measurements, particularly acylcarnitines [87], and inflammatory bowel disease [31], among others. However, as with many GWAS, these associations are primarily drawn from samples of European ancestry. Thus, further studies in diverse populations are needed to continue to clarify the role of OCTN1 in health and disease.

OCTN1 is associated with a number of pathologies relating to inflammation and autoimmunity. OCTN1 exists within the IBD5 locus, a roughly 250 kb segment of chromosome 5.31q that has been associated with inflammatory bowel disease (IBD), particularly Crohn’s disease (CD) and ulcerative colitis [2]. While these are complex polygenic diseases, a haplotype containing the p.L503F variant of OCTN1 and a promoter region variant (−207G>C) of OCTN2 is associated with susceptibility to CD [2].

In addition to IBD, an intronic variant of SLC22A4 (OCTN1) has been associated with RA in a Japanese population [2]. This variant disrupts a consensus sequence for the hematopoietic transcription factor RUNX1, which is also associated with RA. As a result, transcription of SLC22A4 is suppressed when this intronic variant is present, increasing susceptibility to RA, although full understanding of these associations and mechanisms remains to be elucidated.

OCTN1 contains a number of polymorphisms in various populations. The most common are p.I306T, with a global allele frequency (GAF) of 0.583 according to the GnomAD database [88], and p.L503F, which exists at a GAF of 0.291 with varying frequencies in all ancestral populations [88] (Table 2.3). In vitro, neither polymorphism results in significant alteration in the transport of OCTN1 substrates, betaine or TEA [81]. Conversely, p.L503F has been shown to reduce OCTN1 transport of the anticonvulsant drug gabapentin in vitro and influence the clearance of the gabapentin in vivo. Individuals with the 503L/503L genotype exhibit net secretion of gabapentin by OCTN1 at the apical membrane of the kidney, facilitating elimination of the drug, while individuals homozygous for 503F exhibit no net secretion of gabapentin, with renal clearance roughly equivalent to the rate of glomerular filtration [89].