**6. Genetic Biomarkers**

Some descriptions of the association of ATIN, mainly in the setting of TINU, with certain human leukocyte antigen (HLA) or single-nucleotide polymorphisms (SNPs) as markers of disease susceptibility have been published.

To identify genetic markers of TINU, Levinson et al. performed HLA genotyping of 18 American TINU patients. They found that the disease was strongly associated with HLA-DQA1\*01, HLA-DQB1\*05, and HLA-DRB1\*01. The prevalence of these HLA genes was elevated among their cohort of TINU patients, and significantly higher in comparison with the published HLA frequencies in North American whites [45]. A study conducted in a cohort of 154 Chinese patients with ATIN of different causes showed that, similarly to the American study, HLA-DQA1\*0104/DQB1\*0503/DRB1\*1405 are risk haplotypes for the development of ATIN. These studies suggest that these variants may enhance antigen presentation and facilitate renal tubulointerstitial inflammation.

Rytkönen et al. studied IL-10 gene SNPs in a cohort of 30 pediatric cases of TINU or idiopathic TIN. They found a higher prevalence of the IL-10 SNP s3024490 in TINU/ATIN cases compared with its prevalence in a control group of 393 individuals from their own population [46]. IL-10 is an immunoregulatory cytokine that inhibits the synthesis of proinflammatory cytokines and chemokines. Interestingly, IL-10 SNPs have also been linked to susceptibility to recurrent attacks of acute pyelonephritis [47]. Based on these findings, the authors suggested that patients with SNPs in immunoregulatory cytokines and other inflammatory mediators may confer higher susceptibility to TINU/ATIN.
