br Acknowledgments br Introduction Psoriatic skin lesions ar

Acknowledgments
Introduction Psoriatic skin lesions are characterized by histological evidence of inflammation, abnormal keratinocyte proliferation/terminal differentiation, and dermal angiogenesis. Although the etiology of psoriasis remains unknown, it is clear that an interaction among genetic susceptibility variants, the immune system, and environmental factors contribute to the development of the chronic inflammatory process. Human β-defensins (hBDs) are a family of small, secreted antimicrobial peptides. In addition to antibacterial and antiviral effects, β-defensins have been shown to be involved in the immunological reactions that protect the host from various pathogens. The expression of hBD-1 is generally constitutive, and the level of hBD-2 is thought to be induced by proinflammatory cytokines and bacteria. Histologically, hBDs are expressed by epithelial prostaglandin synthase of the skin, gut, respiratory tissue, and urogenital tissue. In addition to epithelial cells, the expression of hBD-1 and hBD-2 have also been found in human monocytes, macrophages, and dendritic cells (DCs). HBDs are encoded by DEFB genes in three main gene clusters: two on chromosome 20 and one on chromosome 8p23.1. Of the eight β-defensin genes at 8p23.1, not including DEFB1 (encoding the protein hBD-1) but including DEFB4 (encoding the protein hBD-2), SPAG11, DEFB103 (encoding the protein hBD-3), DEFB104 (encoding the protein hBD-4), DEFB105, DEFB106, and DEFB107, are on a large repeat unit that varies in copy number. In humans, up to 12 copies of this repeat have been found, and three to five copies per diploid genome are more prevalent. HBD-2, hBD-3, and hBD-4 have been demonstrated to stimulate keratinocytes to release interleukin (IL) IL-8, IL-18, and IL-20, which are all proinflammatory cytokines that have an established role in the pathogenesis of psoriasis. Recently, Hollox et al found an association between higher copy number variations (CNVs) for DEFBs on chromosome 8p23.1 and risk of psoriasis in a Caucasian population. However, the relationship of DEFBs CNVs and psoriasis, until now, remains unclear in the Chinese population. Further, the role of the DEFB1 gene as a potential modifier in psoriasis has not previously been studied. Three singe nucleotide polymorphisms (SNPs) at positions c.-20G>A (rs11362), c.-44C>G (rs1800972), and c.-52G>A (rs1799946) in the 5\'-untranslated region of DEFB1 gene have been described to influence the hBD-1 expression or function. Recent studies in the Mexican, Egyptian, and Korean populations have identified an association between DEFB1 SNPs and the susceptibility of atopic dermatitis, which shares with psoriasis the similar phenotypes of dry, scaly skin and disturbed epidermal differentiation. We, therefore, consider it to be important to investigate the relevance of the SNPs of the DEFB1 gene and the CNVs of the DEB4 genes in patients with psoriasis among the Taiwanese population.
Methods
Results Table 1 lists the characteristics of the cases and control participants. There was no significant difference between the two groups with regard to gender, age, hypertension, diabetes, smoking, and BMI. The distributions of the DEFB4 genomic copy number in the study population, shown in Figure 1, exhibited a range of 2–11 per genome, with a median number of five copies. The difference in overall DEFB4 genomic copy number distribution between psoriasis patients and control participants was insignificant, as determined with the Kolmogorov–Smirnov test (p = 0.657). The proportions of control individuals who carried a number of copies less than the median (< 5) or greater than median (≥ 5) were 42.9% and 57.1%, respectively. In the patients with psoriasis, the frequency of distribution of the subgroup (38.8% and 61.2%) did not significantly differ from that of the control group (p = 0.411; Figure 2). Individuals with a copy number ≥ 5 had an insignificantly higher risk of psoriasis than did individuals with a copy number < 5 (odds ratio = 1.18, 95% confidence interval = 0.79–1.77). The average number of copies per genome in psoriasis patients was slightly greater than that of the control participants (5.14 ± 2.01 vs. 5.02 ± 1.75), but the difference did not reach statistical significance (p = 0.520). In the logistic regression analysis with the DEFB4 CNVs as an integer variable, they were also not associated with psoriasis after adjusting for age, sex, smoking, diabetes, hypertension, and BMI (odds ratio = 1.03, 95% confidence interval = 0.89–1.19, p = 0.720). Additionally, comparison between the disease subgroup (i.e., early/late onset and severity of psoriasis) among psoriasis patients, revealed no significant difference in the frequencies of the carriers with a copy number ≥ 5 (data not shown).