Immunization Associated with Erectile Dysfunction Based on Cross-Sectional and Genetic Analyses

<div><p>Erectile dysfunction (ED) is a global disease affecting a large number of people. Some studies have found a relationship between low-grade inflammation and ED. We hypothesized that the immune system might play a key role in the outcome of ED. Five immune agents (C3, C4, IgA, IgM, and IgG) were collected based on the Fangchenggang Area Male Health and Examination Survey (FAMHES), using methods of a traditional cross-sectional analysis. Our results repeated the significant association between ED and metabolic syndrome, obesity, and so forth. However, there seemed to be no positive relation between the tested indexes and ED risk in the baseline analysis (C3: <i>P</i> = 0.737; C4: <i>P</i> = 0.274; IgA: <i>P</i> = 0.943; IgG: <i>P</i> = 0.069; IgM: <i>P</i> = 0.985). Then, after adjusting for age and multivariate covariates, a potentially significant association between ED and IgG was discovered (<i>P</i> = 0.025 and <i>P</i> = 0.034, respectively). Meanwhile, in order to describe the development of ED on a gene level, SNP–set kernel-machine association test (SKAT) was applied with the known humoral immune genes involved. The outcomes suggested that PTAFR (binary <i>P</i> value: 0.0096; continuous <i>P</i> value: 0.00869), IL27 (0.0029; 0.1954), CD37 (0.0248; 0.5196), CD40 (0.7146; 0.0413), IL7R (0.1223; 0.0222), PSMB9 (0.1237; 0.0212), and CXCR3 (0.0849; 0.0478) might be key genes in ED, especially IL27, when we restricted the family-wise error rate (FWER) to 0.5. Our study shows that IgG and seven genes (PTAFR, CD37, CD40, IL7R, PSMB9, CXCR3, and especially IL27) might be key factors in the pathogenesis of ED, which could pave the way for future gene and immune therapies.</p></div

By comparing the P-value of each test to the distribution of the minimum P-values obtaining from 1000 permuted data sets Family wise error rate (FWER) was applied with the SKAT in binary and continuous group.

<p>By comparing the P-value of each test to the distribution of the minimum P-values obtaining from 1000 permuted data sets Family wise error rate (FWER) was applied with the SKAT in binary and continuous group.</p

Association between immune substances and IIEF-5 score of ED in the multivariate regression analysis.

<p>Association between immune substances and IIEF-5 score of ED in the multivariate regression analysis.</p

Characteristics of the eligible samples in this analysis for IgG and erectile dysfunction.

<p>Characteristics of the eligible samples in this analysis for IgG and erectile dysfunction.</p

The tendency of the morbidity of erectile dysfunction (ED) along with age growth.

<p>* X-axis stands for ages with 10 years range difference. * There are two Y-axes. On the left, the axis stands for the counts of ED or no-ED patients. As for the right one, it represents the morbidity of ED in different age brackets.</p

The significant association for the genes of humoral immunity and ED.

<p>The significant association for the genes of humoral immunity and ED.</p

Association between immune substances and ED in the multivariate logistic regression analysis.

<p>Association between immune substances and ED in the multivariate logistic regression analysis.</p

Subgroup analysis of association between ED and FT, BT in the univariate binary logistic models.

<p>TT = total testosterone, FT = free testosterone, BT = bioavailable testosterone, SHBG = sex hormone-binding globulin, BP = blood pressure, HDL-C = high-density lipoprotein cholesterol.</p

Characteristics of the analysis sample at baseline in FAMHES^*.

†<p>Age was present as median values (25–75th percentile); sex hormones including TT, BT and SHBG were logarithmically transformed in the following analysis and reported as back-transformed arithmetic mean values ± SD (standard deviation).</p>*<p>FAMHES =  the Fangchenggang Area Male Health and Examination Survey, TT = total testosterone, FT = free testosterone, BT = bioavailable testosterone, SHBG = sex hormone-binding globulin, BP = blood pressure, HDL-C = high-density lipoprotein cholesterol. TT and FT values divide by 3.467 can be converted to ng/ml.</p

Association between testosterone and ED in the multivariate regression analysis ^†.

†<p>Multivariate adjusted for age, smoking status, alcoholic drinking, hypertriglyceridemia, hyperglycemia, elevated BP, low HDL-C and central obesity. Linear regression is conducted using the IIEF-5 score as a continuous variable, whereas the binary logistic regression is conducted using ED defined as a dichotomous variable using a cut-off point of IIEF-5<22. ED = erectile dysfunction; IIEF-5 = 5-item International Index of Erectile Function; TT = total testosterone; FT = free testosterone; BT = bioavailable testosterone; BP = blood pressure, HDL-C = high-density lipoprotein cholesterol.</p