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

Abstract

BACKGROUNDChronic inflammation and obesity may contribute to the genesis or progression of benign prostatic hyperplasia (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, RNASEL) and genes involved in obesity, including insulin regulation (LEP, ADIPOQ, PPARG, TCF7L2), with BPH.METHODSBPH 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 (OR) and 95% confidence intervals (CI) were estimated using logistic regression.RESULTSNone 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; Ptrend=0.006).CONCLUSIONSNPs in genes related to immune response and obesity, especially in combination, may be associated with BPH.

A genetic variant nearGATA3implicated in inherited susceptibility and etiology of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS)

“…The demographic information of the study populations is shown in Table . The detailed characteristics of the CLUE II study population and Finnish population have been described in previous studies …”

“…The detailed characteristics of the CLUE II study population and Finnish population have been described in previous studies. 17,19,20 To initially identify candidate genetic variants in the form of SNPs that may be associated with BPH/LUTS, we performed GWAS Fig. S1).…”

“…The characteristics of the study population from CLUE II were described in a previous publication . Briefly, this was a community cohort with 32 898 volunteers who were recruited in Washington County, MD from May through October 1989.…”

“…The characteristics of the study population from CLUE II were described in a previous publication. 17 Briefly, this was a community cohort with 32 898 volunteers who were recruited in Washington Index ≥15 (high-moderate to severe symptoms). A total of 568 men met these criteria, as well as a group of age-and race-paired control men (n = 568) who were also included.…”

Disparities in pancreatic cancer care and research in Native Americans: Righting a history of wrongs

“…41 Although some individuals of NA/AN descent were included, they ultimately comprised 1.3% of the non-African American cohort, or 300 individuals. The inclusion of even fewer NA/ANs is seen in other large historical cohort studies, such as the CLUE II cohort, which was 98.8% White, 42 or the National Institutes of Health-American Association of Retired Persons Diet and Health Study, which was 99% White, Hispanic, and African American, with the remaining 1% labeled as Asian/other. 43 A full list of population-level studies in the United States that have not included NA/AN populations is outside the scope of this article.…”