A multicenter case–control study of the effect of e-nos VNTR polymorphism on upper gastrointestinal hemorrhage in NSAID users

Bleeding in non-steroidal anti-inflammatory drug (NSAID) users limited their prescription. This first multicenter full case–control study (325 cases and 744 controls), explored the association of e-NOS intron 4 variable number tandem repeat (VNTR) polymorphism with upper gastrointestinal hemorrhage (UGIH) in NSAID exposed and unexposed populations and assessed any interaction between this polymorphism and NSAIDs. NSAID users carrying e-NOS intron 4 wild type genotype or VNTR polymorphism have higher odds of UGIH than those unexposed to NSAIDs [Odds Ratio (OR): 6.62 (95% Confidence Interval (CI): 4.24, 10.36) and OR: 5.41 (95% CI 2.62, 11.51), respectively], with no effect modification from VNTR polymorphism-NSAIDs interaction [Relative Excess Risk due to Interaction (RERI): −1.35 (95% CI −5.73, 3.03); Synergism Index (S): 0.77 (95% CI 0.31, 1.94)]. Similar findings were obtained for aspirin exposure. Non-aspirin NSAID users who carry e-NOS intron 4 VNTR polymorphism have lower odds of UGIH [OR: 4.02 (95% CI 1.85, 8.75) than those users with wild type genotype [OR: 6.52 (95% CI 4.09, 10.38)]; though the interaction estimates are not statistically significant [RERI: −2.68 (95% CI −6.67, 1.31); S: 0.53 (95% CI 0.18, 1.55)]. This exploratory study suggests that the odds of UGIH in NSAID or aspirin users does not modify according to patient´s e-NOS intron 4 genotype.

Association between the Interleukin-1 Receptor Antagonist (IL1RN) Variable Number of Tandem Repeats (VNTR) Polymorphism and Lymphoma

Introduction: Lymphoma is a common hematopoietic cancer. Immunosuppression is one of the main risk factors for the development of lymphoma. The interleukin (IL)-1 receptor antagonist IL1RN, which binds to the IL-1 receptor, moderates a variety of immune responses related to IL-1. We aimed to assess the impact of IL1RN variable number of tandem repeats (VNTR) polymorphism on lymphoma risk in an Iranian population sample. Materials and Methods: DNA was extracted from peripheral blood of 120 subjects with non-Hodgkin Lymphoma (NHL), 50 subjects with Hodgkin’s lymphoma (HL), and 186 unrelated healthy individuals. IL1RN VNTR polymorphism was detected using polymerase chain reaction. Results: Our findings revealed that the IL1RN VNTR polymorphism was associated with protection against NHL (P≤0.001, OR: 0.30, 95% CI: 0.18-0.53). The IL1RN 2 allele significantly decreased the risk of NHL (p = 0.023, OR = 0.66, 95%CI = 0.46–0.93). In addition, we found that IL1RN 1/2 was associated with a lower risk of HL (p ≤0.001, OR = 0.24, 95%CI = 0.12–0.50). Conclusion: Our results suggest that the presence of IL1RN VNTR polymorphism is associated with a decreased risk of lymphoma in an Iranian subpopulation in southeast Iran.

Association of DRD2 (rs 1799732), ANKK1 (rs1800497), DAT (rs28363170), DRD4 (exon 3 - VNTR) gene polymorphisms in the context of relapses in therapy.

Introduction: Disorders in the field of reward system neurotransmission are mentioned as one of the most important causes of addiction. Genetic variation is assigned a special role. The literature on the subject mentions primarily the genes of dopamine neurotransmission: DAT (dopamine transporter), DRD2 (dopamine receptor D2), DRD4 (dopamine receptor D4). However, so far there are few literature reports on these genes in the context of innovators in addiction therapy. The aim: Analysis of the relationship between the variability of specific polymorphisms in the DRD2 (rs1799732), ANKK1 (rs1800497), DAT (rs28363170), DRD4 (exon 3 - VNTR) genes with the occurrence of relapses in people addicted to psychoactive substances. Material and methods: The research was carried out on a group of 301 people addicted to psychoactive substances staying in an addiction therapy center in Lubuskie and Zachodniopomorskie voivodships in Poland. The control group consisted of 301 people with no diagnosed addiction to psychoactive substances nor mental disorders. The study of polymorphisms DRD2 (rs 1799732), ANKK1 (rs1800497) was performed by real-time PCR method; whereas DAT (rs28363170), DRD4 (exon 3 - VNTR) was genotyped by PCR and the amplified products were visualized using ethidium bromide stained gel electrophoresis (3% agarose) and UV photography. Results: This study showed that in addicts genotype frequencies of the VNTR polymorphism in the third exon of human DRD4 were as follow: S/L in 33.55%, S/S - 63.12% and L/L 3.32%; while in the control group S/L - 32.56%, S/S - 58.8 % and L/L -8.6% (χ2 = 7.617, p = 0.022). Significant differences in the frequency of DRD2 gene polymorphism rs1799732 were observed (frequency of alleles; χ2 = 5.48, p = 0.0192) and DRD4 VNTR polymorphism (χ2 = 7.687, p = 0.021) between the addicted to psychoactive substances who have a one-time stay in an inpatient treatment center and the control group.