在CLUE II研究中，免疫反应和肥胖相关基因变异与良性前列腺增生的关联。
Association of variants in genes related to the immune response and obesity with BPH in CLUE II.
作者信息
Lopez D S, Peskoe S B, Tsilidis K K, Hoffman-Bolton J, Helzlsouer K J, Isaacs W B, Smith M W, Platz E A
机构信息
1] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA [2] Division of Epidemiology, University of Texas School of Public Health, Houston, TX, USA [3] Division of Urology, University of Texas Medical School, Houston, TX, USA.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
出版信息
Prostate Cancer Prostatic Dis. 2014 Dec;17(4):353-8. doi: 10.1038/pcan.2014.36. Epub 2014 Sep 16.
BACKGROUND
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.
METHODS
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.
RESULTS
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).
CONCLUSIONS
SNPs in genes related to immune response and obesity, especially in combination, may be associated with BPH.
背景
慢性炎症和肥胖可能促使良性前列腺增生（BPH）及其相关下尿路症状（LUTS）的发生或进展。与这些状态相关的基因变异对BPH的影响尚未得到广泛研究。因此，我们评估了免疫反应基因（IL1B、IL6、IL8、IL10、TNF、CRP、TLR4和RNASEL）以及参与肥胖的基因（包括胰岛素调节相关基因LEP、ADIPOQ、PPARG和TCF7L2）中的17个单核苷酸多态性（SNP）与BPH的关联。
方法
从2000年回复邮寄问卷的成年男性CLUE II队列参与者中选取BPH病例（N = 568）和年龄频率匹配的对照（N = 568）。BPH定义为接受BPH手术、使用BPH药物或有症状的BPH（美国泌尿外科学会症状指数评分⩾15）。对照为未接受BPH手术、未使用BPH药物且症状评分为⩽7的男性。使用逻辑回归估计年龄调整后的比值比（OR）和95%置信区间（CI）。
结果
没有一个候选SNP与BPH有统计学显著关联。然而，我们不能排除CRP rs1205（1082C>T）、ADIPOQ rs1501299（276C>A）、PPARG rs1801282（-49C>G）和TCF7L2 rs7903146（47833T>C）可能存在的弱关联。在对风险等位基因进行汇总后，与携带⩽1个风险等位基因的男性相比，携带⩾4个风险等位基因的男性患BPH的风险增加（OR，1.78；95%CI，1.10 - 2.89；P（趋势）= 0.006）。
结论
与免疫反应和肥胖相关基因中的SNP，尤其是联合起来，可能与BPH有关。
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