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Association of variants in genes related to the immune response and obesity with BPH in CLUE II.

ABSTRACT: Chronic inflammation and obesity may contribute to the genesis or progression of BPH and BPH-associated lower urinary tract symptoms (LUTS). The influence of variants in genes related to these states on BPH has not been studied extensively. Thus, we evaluated the association of 17 single-nucleotide polymorphisms (SNPs) in immune response genes (IL1B, IL6, IL8, IL10, TNF, CRP, TLR4 and RNASEL) and genes involved in obesity, including insulin regulation (LEP, ADIPOQ, PPARG and TCF7L2), with BPH.BPH cases (N = 568) and age-frequency matched controls (N=568) were selected from among adult male CLUE II cohort participants who responded in 2000 to a mailed questionnaire. BPH was defined as BPH surgery, use of BPH medications or symptomatic BPH (American Urological Association Symptom Index Score ? 15). Controls were men who had not had BPH surgery, did not use BPH medications and whose symptom score was ? 7. Age-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression.None of the candidate SNPs was statistically significantly associated with BPH. However, we could not rule out possible weak associations for CRP rs1205 (1082C>T), ADIPOQ rs1501299 (276C>A), PPARG rs1801282 (-49C>G) and TCF7L2 rs7903146 (47833T>C). After summing risk alleles, men with ? 4 had an increased BPH risk compared with those with ? 1 (OR, 1.78; 95% CI, 1.10-2.89; P(trend) = 0.006).SNPs in genes related to immune response and obesity, especially in combination, may be associated with BPH.

SUBMITTER: Lopez DS

PROVIDER: S-EPMC4227920 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Association of variants in genes related to the immune response and obesity with BPH in CLUE II.

Lopez D S DS Peskoe S B SB Tsilidis K K KK Hoffman-Bolton J J Helzlsouer K J KJ Isaacs W B WB Smith M W MW Platz E A EA

Prostate cancer and prostatic diseases 20140916 4

<h4>Background</h4>Chronic inflammation and obesity may contribute to the genesis or progression of BPH and BPH-associated lower urinary tract symptoms (LUTS). The influence of variants in genes related to these states on BPH has not been studied extensively. Thus, we evaluated the association of 17 single-nucleotide polymorphisms (SNPs) in immune response genes (IL1B, IL6, IL8, IL10, TNF, CRP, TLR4 and RNASEL) and genes involved in obesity, including insulin regulation (LEP, ADIPOQ, PPARG and T ...[more]

PMID: 25224558

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Project description:Administration of tamoxifen (TAM) as breast cancer adjuvant therapy is associated with a 50% reduction in breast cancer risk and an increase in endometrial cancer risk. To investigate underlying mechanisms, we documented TAM-induced gene expression changes in cultured normal human mammary epithelial cell (NHMEC) strains (numbered 5, 16 and 40) established from tissue taken at reduction mammoplasty from three different individuals. Cells exposed to 0 and 10 uM TAM for 48 hours were evaluated for survival, TAM-DNA adduct formation by TAM-DNA chemiluminescence immunoassay (CIA), and gene expression changes using DNA-oligonucleotide microarray and real time reverse transcriptase-PCR (RT-PCR). At 48 hr, cells exposed to 10 uM TAM were 78% viable, respectively, and there were no measurable TAM-DNA adducts (limit of detection [LOD] = 0.3 adducts/10^8 nucleotides). For microarray analysis, RNA was extracted from cells exposed on three occasions to 10 uM TAM and the corresponding oligonucleotide probes were labeled with fluorescent dyes and hybridized to NCI microarrays (>20,000 human genes). Expression changes of > 3-fold were considered significant, and by these criteria, thirteen genes were up-regulated and one was down-related in NHMEC strain 16, seventeen genes were up-regulated in strain 05, and eleven genes were up-regulated in strain and 40. Elements that were up-regulated in all three cell strains included several interferon-induced genes (IFITM1, IFIT1, IFNA1, MXI and GIP3), and a potassium ion channel (KCNJ1). No significant expression changes were found for genes related to estrogen or xenobiotic metabolism. RT-PCR revealed TAM-induced up-regulation of the five genes of interest, and interferon-α (IFNA1), in all three NHMEC strains, with the exception of GIP3 and MX1, which were unchanged in strain 40. The magnitude of TAM-induced up-regulation ranked: strain 16 > strain 05> strain 40. The consistent induction of interferon-related genes in all three NHMEC strains suggests that, in addition to hormonal effects, TAM exposure may enhance immune response, through interferon induction, in normal breast tissue. RNA was extracted from three cell strains (NHMEC 98016, 98040 and 99005) and exposed on three separate occasions to 10 uM TAM. Comparisons were made using 16 arrays with 8 dye swaps for cell strain NHMEC 99005, 9 arrays with 4 dye swaps for NHMEC 98016, and 12 arrays with 6 dye swaps for NHMEC 98040.

Dataset Information

Association of variants in genes related to the immune response and obesity with BPH in CLUE II.

Publications

Association of variants in genes related to the immune response and obesity with BPH in CLUE II.

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