Although previous research identified candidate genetic polymorphisms associated with cisplatin nephrotoxicity, varying outcome definitions potentially contributed to the variability in the effect size and direction of this relationship. We selected genetic variants that have been significantly associated with cisplatin-induced nephrotoxicity in more than one published study (SLC22A2 rs316019; ERCC1 rs11615 and rs3212986; ERCC2 rs1799793 and rs13181) and performed a replication analysis to confirm associations between these genetic polymorphisms and cisplatin nephrotoxicity using various outcome definitions. We included 282 germ cell testicular cancer patients treated with cisplatin from 2009–2014, aged >17 years recruited by the Canadian Pharmacogenomics Network for Drug Safety. Nephrotoxicity was defined using four grading tools: (1) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 for acute kidney injury (AKI) or CTCAE-AKI; (2) adjusted cisplatin-induced AKI; (3) elevation of serum creatinine; and (4) reduction in the estimated glomerular filtration rate (eGFR). Significant associations were only found when using the CTCAE v4.03 definition: genotype CA of the ERCC1 rs3212986 was associated with decreased risk of cisplatin nephrotoxicity (ORadj = 0.24; 95% CI: 0.08–0.70; p = 0.009) compared to genotype CC. In contrast, addition of allele A at SLC22A2 rs316019 was associated with increased risk (ORadj = 4.41; 95% CI: 1.96–9.88; p < 0.001) while genotype AC was associated with a higher risk of cisplatin nephrotoxicity (ORadj = 5.06; 95% CI: 1.69–15.16; p = 0.004) compared to genotype CC. Our study showed that different case definitions led to variability in the genetic risk ascertainment of cisplatin nephrotoxicity. Therefore, consensus on a set of clinically relevant outcome definitions that all such studies should follow is needed.
It has been suggested that the second (2D, index finger) to fourth (4D, ring finger) digit ratio, 2D : 4D, may be a biomarker for the risk of developing autism. The aim of the current study was to determine the usefulness of the 2D : 4D digit ratio as biomarker for autistic traits. N = 401 healthy young volunteers participated in the study. For both hands, digit lengths were measured using digital Vernier calipers. In addition to demographics, the Autism Spectrum Quotient (AQ) questionnaire was completed, comprised of five subscales, assessing “social insights and behavior,” “attention switching,” “communication,” “imagination,” and “attention to detail.” Overall, no significant correlations were observed between the AQ total score, its subscales, and the 2D : 4D digit ratio. For women, the left hand 2D : 4D digit ratio correlated significantly with the subscale score “communication” (r = −0.142; p = 0.036). For men, a significant positive correlation was found between the left 2D : 4D digit ratio and the total AQ score (r = 0.157; p = 0.042) and AQ subscale “attention switching” (r = 0.182; p = 0.017). In conclusion, gender specific associations between the 2D : 4D digit ratio and specific autism traits were observed, which were stronger in men than in women. Future studies should be conducted in patients that are formally diagnosed with autism.
Altered immune functioning has been demonstrated in individuals with autism spectrum disorder (ASD). The current study explores the relationship between perceived immune functioning and experiencing ASD traits in healthy young adults. N = 410 students from Utrecht University completed a survey on immune functioning and autistic traits. In addition to a 1-item perceived immune functioning rating, the Immune Function Questionnaire (IFQ) was completed to assess perceived immune functioning. The Dutch translation of the Autism-Spectrum Quotient (AQ) was completed to examine variation in autistic traits, including the domains “social insights and behavior”, “difficulties with change”, “communication”, “phantasy and imagination”, and “detail orientation”. The 1-item perceived immune functioning score did not significantly correlate with the total AQ score. However, a significant negative correlation was found between perceived immune functioning and the AQ subscale “difficulties with change” (r = −0.119, p = 0.019). In women, 1-item perceived immune functioning correlated significantly with the AQ subscales “difficulties with change” (r = −0.149, p = 0.029) and “communication” (r = −0.145, p = 0.032). In men, none of the AQ subscales significantly correlated with 1-item perceived immune functioning. In conclusion, a modest relationship between perceived immune functioning and several autistic traits was found.
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