ORIGINAL ARTICLES JAK-1 rs2780895 C-Related Genotype and Allele but Not JAK-1 rs10789166, rs4916008, rs2780885, rs17127114, and rs3806277 Are Associated with Higher Susceptibility to Asthma Yao-Yuan Hsieh, 1,2 Chi-Chen Chang, 2 Chin-Mu Hsu, 1,3 Lei Wan, 1,3 Shih-Yin Chen, 4 Wen-Hsin Lin, 5 and Fuu-Jen Tsai 3,4,6 Background: Asthma, one major respiratory consequence, might be caused by a complex interaction between multiple candidate genes and environmental factors. Herein, we aimed to investigate whether Janus kinase ( JAK)-1 gene polymorphisms are associated with asthma susceptibility. Materials and Methods: Patients were divided into two groups: (1) asthma (n = 117) and (2) nonasthma (n = 60). The JAK-1 polymorphisms (rs2780895, rs10789166, rs4916008, rs2780885, rs17127114, and rs3806277) were amplified by polymerase chain reaction and detected by electrophoresis after restriction enzyme (HpyCH4IV, Tsp45I, HpaII, XmnI, MspI, and HpaII) diges- tions. Genotypes, allelic frequencies, and association of haplotypes in both groups were compared. Results: JAK-1 rs2780895 gene polymorphism is associated with susceptibility to asthma. Distributions of JAK-1 rs2780895*CC/CT/TT and C/T allele in both groups are: (1) 80/4/16% and 82/18%; (2) 48/45/7% and 71/29%. Other 5 JAK-1 SNPs (rs10789166, rs4916008, rs2780885, rs17127114, and rs3806277) are not associated with asthma susceptibilities. Distributions of JAK-1 rs10789166*AA/AG/GG, rs4916008*CC/CT/TT, rs2780885*CC/ CT/TT, rs17127114*AA/AG/GG, rs3806277*AA/AG/GG in both groups are: (1) 50/40/10%, 42/49/9%, 50/ 40/10%, 9/37/54%, 8/35/57%; (2) 43/50/7%, 40/50/10%, 50/43/7%, 7/48/45%, 6/42/52%. Haplotype ana- lyses for JAK-1 gene polymorphisms (rs2780895-rs10789166-rs4916008-rs2780885-rs17127114-rs3806277) re- vealed that JAK-1 haplotypes are not associated with asthma susceptibilities. Conclusions: JAK-1 rs2780895 C-related genotype and allele are associated with higher susceptibility to asthma. JAK-1 rs10789166, rs4916008, rs2780885, rs17127114, and rs3806277 single-nucleotide polymorphisms are not associated with asthma devel- opment. Some JAK-related genetic variations might be associated with asthma pathogenesis, which deserve further surveys. Introduction A sthma, a major respiratory illness, has 6%–9% prevalence in the general population (Moorman et al., 2007). The incidence of asthma increased during the past de- cade (Woolcock and Peat, 1997). Asthma is caused by a complex interaction between multiple candidate genes and environmental factors. The increased incidence of asthma has been attributed to increased environment contamination and overusage of antibiotics as well as constitutional and genetic factors. Genetic studies suggested the functional role of some cytokines upon airway infection and hyperstimulation. However, the related molecular basis for this upper airway disorder remains unclear. The mechanistic roles of these cytokine-associated single-nucleotide polymorphisms (SNPs) have to be yet elucidated, especially in the context of the pathophysiology of asthma. Further, a basis for predicting asthma susceptibilities remains obscure. The Janus kinase ( JAK)/signal transducers and activators of transcription (STAT) cascade is essential for cytokines, growth factors, G-proteins, and hormones (Buslei et al., 2006). The STA of JAK-STAT pathway controls signal transduction 1 School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan. 2 Division of Infertility Clinic, Hsieh Yao-Yuan Womens’ Hospital, Taichung, Taiwan. 3 Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan. 4 Graduate Institute of Chinese Medical Science, China Medical University, China Medical University Hospital, Taichung, Taiwan. 5 School of Pharmacy Undergraduate Program Department of Medicine, China Medical University, Taichung, Taiwan. 6 Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan. GENETIC TESTING AND MOLECULAR BIOMARKERS Volume 15, Number 12, 2011 ª Mary Ann Liebert, Inc. Pp. 841–847 DOI: 10.1089/gtmb.2011.0002 841