Investigating the Contribution of NPSR1, IL-6 and BDNF Polymorphisms to Depressive and Anxiety Symptoms in Hemodialysis Patients

Aims: Psychological symptoms are prevalent in hemodialysis (HD) patients. Previous investigations showed that brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) as well as the interaction with neuropeptide S receptor 1 (NPSR1) are linked to the development of psychological distress. This study examined the association of polymorphisms of genes encoding these proteins with depression and anxiety in a representative group of Jordanian HD patients.

Methods: A total of 302 HD patients were involved in the study and categorized into three groups based on the Hospital Anxiety and Depression Scale, HADS-D or HADS-A scores as follows: normal (<7), mild (8-10) and moderate-severe (11-21). Single nucleotide polymorphism (SNP) of NPSR1 Asn107Ile (rs324981), IL-6 G174C (rs1800795), and BDNF Val66Met (rs6265) was genotyped using blood samples.

Results: The frequency of Ile-allele of NPSR1 Asn107Ile was significantly higher in patients with moderate-severe HADS-A scores versus normal (53% vs. 40.8%, p = .035). Using ordinal regression analysis, Asn-allele of NPSR1 polymorphism was nominally significantly associated with a lower risk of anxiety (OR = 0.57, CI: 0.33-0.97, p = .038) after adjusting for other covariates. A marginally significant difference in genotype distribution of IL-6 G174C was observed among patients according to HADS-D scores (p = .05). Furthermore, carriers of IL-6174 CC genotype showed lower median IL-6 serum concentration versus carriers of GG genotype (5.2 vs. 1.35 pg/mL, p < .05).

Conclusions: The results support the genetic role of NPSR1 in the pathogenesis of anxiety and suggest that carriers of NPSR1 Ile-allele are at increased risk of anxiety in HD patients. Neither BDNF Val66Met nor IL-6 G174C were linked to psychological symptoms. Future studies among other ethnicities are necessary to verify the observations.