Wang IgE-mediated immunologic mechanisms are known to play a key role by triggering the release of mediators that are responsible for allergic symptoms. Transendothelial migration of inflammatory cells and their activation within the reactive tissue are characteristic features, which represent the result of a complex network of interactions between various mediators, cytokines, chemokines, and adhesion molecules. It has been suggested that an imbalance of Th1 and Th2 cells, especially Th2 cells, plays an important role in regulating IgE synthesis and cell recruitment at the sites of inflammation. In allergic rhinitis, many studies have demonstrated that mucosal inflammation is characterized by the tissue infiltration of T-lymphocytes (CD4+ T cells and CD25+ T cells) in the submucosa and epithelium (Durham et al 1992; Varney et al 1992). During past decades, the prevalence of allergic rhinitis has increased, especially in developed and industrialized countries. The complete etiology for the development and expression of atopic disease is not yet understood. Several putative factors have been proposed such as changes in lifestyle; increase in exposure to allergens, pollution, and irritants (smoke, gas, etc); changes in diet responsible for the diminution of protective nutrient intake; decrease in infections; and stress (Bousquet 2001). Thus, interaction between environmental factors and individual susceptibility is essential. This paper reviews recent understanding of the pathogenic mechanisms, which are influenced by a complex immune procedure, including interaction of multiple genes, interaction of environmental and genetic factors, and population heterogeneity. Understanding the etiology of allergic rhinitics will lead to the development of genetically oriented diagnosis and more effective environmental control measures. The genetic characters of allergic rhinitis A genetic background in terms of a family history of atopic disease has been the strongest risk factor for the development of allergic symptoms, irrespective of the varying prevalence and environmental risk factors in different societies. The most convincing evidence for genetic effect in the development of atopy is derived from twin studies. The earliest study by Edfors-Lubs, dating back to 1971, showed the hereditary character of allergic rhinitis in twins (Edfors-Lubs 1971). Later, Hopp and colleagues (1984) found a greater concordance of allergic manifestations in monozygotic than dizygotic twins in terms of correlation 116 coefficient of serum total IgE (0.82 vs 0.52), skin test response (0.82 vs 0.46), and bronchial reactivity to inhaled methacholine (0.67 vs 0.34). Atopy is a key condition in the development of allergic diseases, particularly with the IgE-mediated mechanism. It is a disorder with strong familial tendency, usually starting in childhood or adolescence, when patients become sensitized and produce IgE antibodies in response to ordinary allergens (Johannson et al 2004). The complex mechanisms of inheritance, from genetic predisposition of atopy to atopic (allergic) diseases, are still incompletely understood (Figure 1). Some studies suggest that the pathogenesis of allergic diseases is complex and may be caused by a contribution of genetic and environmental factors, especially at the stage of allergen sensitization. In the area of human genetic study, many candidate genes have been identified using position cloning and linkage analysis techniques (Moffatt and Cookson 1999; Peden 2002; Toda and Ono 2002). The genome-wide search approach has shown an association between certain phenotypes of allergic diseases (rhinitis and/or asthma) with markers on more than 14 pairs of chromosomes (ie, chromosome 1, 2, 3, 5, 6, 7, 9, 11, 12, 13, 14, 16, 17, 19, and more). Some of these genes are involved in the specific immune response (ie, HLA-D, TCR, CD14, toll-like receptor, STAT6) and Th1/Th2 cell differentiation; others are genes coding the (total) IgE response or functions of the IgE receptors (ie, IL-4, IL-4R, FcεRIβ, FcepsilonRI) and genes involved in the inflammatory process (TNF-γ, IFN-γ, IL-3) (Cookson et al 1989; Marsh et al 1994; Barnes et al 1996; Noguchi et al 1997, 1998b; Baldini et al 1999; Deichmann et al 1999; Shek et al 2001; Nisiyama et al 2004; Park et al 2004; Weidinger et al 2004; Pykalainen et al 2005). However, studies on association of allergic manifestations with candidate gene polymorphisms have yielded conflicting results. Limited sample size with insufficient statistical power is always a critical methodological issue, which is often neglected in some of the case-control or population- based studies. Various ethnic background influences the outcome of genetic epidemiological studies. There is the presence of a large difference in allele distribution of several allergy- related gene (eg, IL-4 and IL-4-R gene) polymorphisms among various ethnic populations. For the IL-4 gene, a C to T polymorphism at IL-4/-590 was reported to be associated with serum total IgE level (Rosenwasser et al 1995), development of asthma (Noguchi et al 1998a), and atopic dermatitis (Kawashima et al 1998). It seems that T allele Therapeutics and Clinical Risk Management 2005:1(2)