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A meta-analysis: association between Beta-2 adrenergic receptor Arg16Gly polymorphism and asthma in China

Abstract

For different populations, the association studies between the beta-2 adrenergic receptor (ADRB2) Arg16Gly mutation and asthma are conflict. This study was designated to evaluate ADRB2 Arg16Gly polymorphism and asthma in Chinese population. Systemic assessment was performed based on the data from PubMed, Embase, Web of Science, the Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI) up to January 2019. Odds ratios (ORs) with their 95% confidence intervals (95% CIs) were calculated using STATA software. This meta-analysis included 6143 asthma patients and 5919 healthy persons from 34 studies. Overall, ADRB2 Arg16Gly polymorphism showed no significant influence on asthma in China. However, subgroup analyses according to geographic areas, age group and HWE in controls, only found a borderline significant effect for southern Chinese under the homozygotes genetic model (OR = 0.82, 95%CI = 0.68-1.00, P = 0.046). This meta-analysis suggests that ADRB2 Arg16Gly polymorphism is not be related to the development of asthma in China.

Keywords:
ADRB2 Arg16Gly; polymorphism; asthma; meta-analysis; Chinese

1 Introduction

Asthma is a kind of allergic disease of the respiratory tract, and has become a global public health problem in recent years (To et al., 2012To, T., Stanojevic, S., Moores, G., Gershon, A. S., Bateman, E. D., Cruz, A. A., & Boulet, L. P. (2012). Global asthma prevalence in adults: findings from the cross-sectional world health survey. BMC Public Health, 12(1), 204. http://dx.doi.org/10.1186/1471-2458-12-204. PMid:22429515.
http://dx.doi.org/10.1186/1471-2458-12-2...
). The prevalence of asthma is 0.2-21.0% wordwide, which is still increased, especially in developing countries such as China (To et al., 2012To, T., Stanojevic, S., Moores, G., Gershon, A. S., Bateman, E. D., Cruz, A. A., & Boulet, L. P. (2012). Global asthma prevalence in adults: findings from the cross-sectional world health survey. BMC Public Health, 12(1), 204. http://dx.doi.org/10.1186/1471-2458-12-204. PMid:22429515.
http://dx.doi.org/10.1186/1471-2458-12-2...
; Pearce et al., 2007Pearce, N., Ait-Khaled, N., Beasley, R., Mallol, J., Keil, U., Mitchell, E., & Robertson, C., (2007). Worldwide trends in the prevalence of asthma symptoms: phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax, 62(9), 758-766. http://dx.doi.org/10.1136/thx.2006.070169. PMid:17504817.
http://dx.doi.org/10.1136/thx.2006.07016...
; Yangzong et al., 2012Yangzong, Y., Shi, Z., Nafstad, P., Haheim, L. L., Luobu, O., & Bjertness, E. (2012). The prevalence of childhood asthma in China: a systematic review. BMC Public Health, 12(1), 860. http://dx.doi.org/10.1186/1471-2458-12-860. PMid:23050953.
http://dx.doi.org/10.1186/1471-2458-12-8...
). So far, numerous reports demonstrated that multiple genetic variations are involved in asthma. Among these genetic variations, the polymorphisms in beta-2 adrenergic receptor (ADRB2) have been most evaluated in asthma. For instance, single nucleotide polymorphisms of ADRB2 in the coding gene region including Arg16Gly (A46G, rs1042713), Gln27Glu (C79G, rs1042714), Thr164Ile (C491T, rs1800888) and Arg19Cys (T-47C, rs1042711) have proven the influence of ADRB2 activation on the small airways, suggesting the effective therapy of ADRB2 agonists in asthma (Pignatti 2004Pignatti, P. F. (2004). Trends in pharmacogenomics of drugs used in the treatment of asthma. Pharmacological Research, 49(4), 343-349. http://dx.doi.org/10.1016/j.phrs.2003.04.002. PMid:15202513.
http://dx.doi.org/10.1016/j.phrs.2003.04...
; Gao et al., 2004Gao, J. M., Lin, Y. G., Qiu, C. C., Liu, Y. W., Ma, Y., & Liu, Y. (2004). Beta2-adrenergic receptor gene polymorphism in Chinese Northern asthmatics. Chinese Medical Sciences Journal, 19(3), 164-169. PMid:15506640.). Notably, the mutation of the Arg16Gly located at the ADRB2 gene has been extensively examined in studies on ADRB2 polymorphisms in asthma. The potential relationships on ADRB2 Arg16Gly polymorphism and asthma risk among Chinese people being remain conflicting. To our knowledge, it had lower statistical effect on the result than using a meta-analysis while the sample sizes in the individual studies are small. Therefore, this meta-analysis was performed to understand the importance of ADRB2 Arg16Gly polymorphism for asthma risk in Chinese population.

2 Materials and methods

2.1 Data collection

To evaluate the associations between ADRB2 Arg16Gly polymorphism and asthma risk, PubMed, Embase, Web of Science, the Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI) prior to January 2019 were searched using terms: (“asthma” or “asthmatic”) and (“beta-2 adrenergic receptor” or “ADRB2” or “b2-AR”) and “polymorphism” and (“Chinese” or “China”). The search had no restriction in language or publication status.

Inclusion standards: (1) studies examining the relationship between ADRB2 Arg16Gly polymorphism and asthma, (2) study design with the case-control, (3) sufficient data of genotype frequency, (3) Chinese individuals. Exclusion standards: (1) overlapped literatures, (2) unextractable data, (3) not a case-control design, (4) abstract or reviews. The potentially relevant studies and extracted data from the identified publications, including first author’s name, publication year, geographic areas, age group, sample size, and available genotype information from ADRB2 Arg16Gly polymorphism were screened by the investigators.

2.2 Statistical analysis

Data were analyzed by STATA version 12 (StataCorp LP, College Station, TX, USA). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and analyzed by Z-test. The model of G versus A, GG versus AA, GG versus (AA+AG) and (GG+AG) versus AA were examined with the asthma risk, respectively. Heterogeneity and Hardy-Weinberg equilibrium (HWE) were evaluated by I-squared based on Q and the df. When Pheterogeneity< 0.1 or I2 > 50%, a random-effects meta-analysis model was performed to estimate the pooled ORs; if not, a fixed-effects model was used. Pooled ORs were collected for the sensitivity assay. A p-value < 0.05 showed the significant change.

3 Results

3.1 Characteristics of obtained reports

Through research, a total of 232 published articles assessing ADRB2 polymorphisms together with asthma were found. In total, 34 studies (Gao et al., 2000Gao, G., Wang, S., & Zhang, J. (2000). Study on beta 2 adrenergic receptor genetic polymorphisms in asthmatics in the people of the Han nationality of northern China. Zhonghua Jie He He Hu Xi Za Zhi, 23(2), 93-97. PMid:11778498.; Liao et al., 2001Liao, W., Li, W. M., Zhao, C. M., Guang, L. X., Yin, X. J., Ai, Y. P., & Xi, M. (2001). Preliminary Study on the relationship between b2-adrenergic receptors genetic polymorphisms and asthma in children of Han nationality of Chongqing. Journal of Third Military Medical University, 23, 968-971.; Xing et al., 2001Xing, J., Wang, C., Liu, J. Z., Yan, M., Huang, K. W., & Xiao, B. (2001). Association of receptor gene polymorphisms with asthma in Northern Chinese Han Population. Zhonghua Nei Ke Za Zhi, 40, 340-342.; Wang et al., 2001Wang, Z., Chen, C., Niu, T., Wu, D., Yang, J., Wang, B., Fang, Z., Yandava, C. N., Drazen, J. M., Weiss, S. T., & Xu, X. (2001). Association of asthma with beta(2)-adrenergic receptor gene polymorphism and cigarette smoking. American Journal of Respiratory and Critical Care Medicine, 163(6), 1404-1409. http://dx.doi.org/10.1164/ajrccm.163.6.2001101. PMid:11371409.
http://dx.doi.org/10.1164/ajrccm.163.6.2...
; Dai et al., 2002Dai, L. M., Wang, Z. L., Zhang, Y. P., Li, W., Zhao, Z. H., & Liu, L. (2002). Association of beta2 receptor gene polymorphisms with lung function in asthma patients. Zhonghua Jie He He Hu Xi Za Zhi, 25, 554-555.; Leung et al., 2003Leung, T. F., Tang, N. L., Chan, I. H., Li, A. M., Ha, G., Lam, C. W., & Fok, T. F. (2003). Distribution in allele frequencies of predisposition-to-atopy genotypes in Chinese children. Pediatric Pulmonology, 34(6), 419-424. http://dx.doi.org/10.1002/ppul.10210. PMid:12422339.
http://dx.doi.org/10.1002/ppul.10210...
; Lin et al., 2003Lin, Y. C., Lu, C. C., Shen, C. Y., Lei, H. Y., Guo, Y. L., & Su, H. J. (2003). Roles of genotypes of beta2-adrenergic receptor in the relationship between eosinophil counts and lung function in Taiwanese adolescents. The Journal of Asthma, 40(3), 265-272. http://dx.doi.org/10.1081/JAS-120018323. PMid:12807170.
http://dx.doi.org/10.1081/JAS-120018323...
; Wang et al., 2004Wang, W., Wufuer, H. M. T. L., Shabiti, Y. L. H. M. J., Xiang, Y. B., & Abula, A. B. L. K. M. (2004). Association between the genetic polymorphisms of b2-adrenergic receptor gene and the asthma susceptibility and clinical phenotypes in Uygur population. Journal of Cardiovascular and Pulmonary Diseases, 23, 147-152.; Gao et al., 2004Gao, J. M., Lin, Y. G., Qiu, C. C., Liu, Y. W., Ma, Y., & Liu, Y. (2004). Beta2-adrenergic receptor gene polymorphism in Chinese Northern asthmatics. Chinese Medical Sciences Journal, 19(3), 164-169. PMid:15506640.; Cui et al., 2007Cui, L. Y., Liu, X. H., Gao, L. X., & Fan, D. S. (2007). Study on the Association between b2-adrenergic Receptor Genetic polymorphisms and asthma in the population of Inner Mongolia. Chinese journal of Clinical Medicin, 14, 477-481.; Ye et al., 2011Ye, X. W., Feng, D. X., Zhang, X. Y., Yu, H., & Xu, M. (2011). Study on the Relationship between b2-adrenergic Receptor Genetic polymorphisms and asthma a in Miao Nationality. The Journal of Medical Research, 40, 83-85.; Zhang et al., 2008Zhang, X. Y., Zhao, W. L., Gui, Q., He, N. H. (2008). Relationship between genetic polymorphisms of b2-adrenergic receptor and childhood asthma. Journal of Clinical Pediatrics, 26, 399-402.; Yang et al., 2012Yang, Z., Zhang, H., Wang, W., Yin, Y., Wang, J., Zhang, L., Wu, Y. F., & Jiang, F. (2012). Effect of b2-adrenergic receptor polymorphisms on childhood asthma and therapeutic efficacy of long acting b2-agonist. Journal of Clinical Pediatrics, 30, 739-743.; Feng et al., 2004Feng, D. X., Ye, X. W., Zhang, X. Y., Yu, H., Diao, X. Y., Zhang, X. R., & Luo, R. R. (2004). Study on b2-adrenergic Receptor Genetic Polymorphisms and Asthma. Journal of Modern Clinical Medical Bioengineering, 10, 5-7.; He et al., 2012He, X. Q., Li, F. X., Tan, J. Y., & Yang, X. X. (2012). Association of single nucleotide polymorphisms of ADRB2 Arg16Gly with asthma in southern Chinese population. Immunological Journal, 28, 687-690, 702.; Xie et al., 2008Xie, Y., Yang, Z. Z., Chai, B. C. (2008). Relationship of Genetic Polymorphisms of b2 -Adrenergic Receptor and Asthma in Children in Shanghai Area. Journal of Applied Clinical Pediatrics, 23, 272-273.; Liu et al., 2009Liu, L., Fang, L. Z., & Dai, L. M. (2009). Combination Effect of Gene Polymorphisms in 16 Position of b2-adenergic Receptor and Cigarette Smoking on Asthma in Chinese Han Individuals. Medical Recapitulate, 15, 1247-1250.; Shi & Zhou 2008Shi, X. H., & Zhou, J. P. (2008). Association of IL-13 and beta2 receptor gene polymorphisms with asthma. Shandong Yiyao, 48, 119-121.; Tuerxun et al., 2007Tuerxun, K. L. B. N., Shabiti, Y. L. H. M., Wang, W., & Wufuer, H. M. T. L. (2007). Study on the b2AR polymorphism in asthmatic abnormal black savda patients. Xinjiang Yike Daxue Xuebao, 30, 945-948.; Zheng et al., 2012Zheng, B. Q., Wang, G. L., Yang, S., Lu, Y. Q., Liu, R. J., & Li, Y. (2012). Study of genetic susceptibility in 198 children with asthma. Zhongguo Dang Dai Er Ke Za Zhi, 14(11), 811-814. PMid:23146724.; Fu et al., 2011Fu, W. P., Zhao, Z. H., Zhong, L., Sun, C., Fang, L. Z., Liu, L., Zhang, J. Q., Wang, L., Shu, J. K., Wang, X. M., & Dai, L. M. (2011). Relationship between polymorphisms in the 5′ leader cistron, positions 16 and 27 of the adrenergic β2 receptor gene and asthma in a Han population from southwest China. Respirology (Carlton, Vic.), 16(8), 1221-1227. http://dx.doi.org/10.1111/j.1440-1843.2011.02028.x. PMid:21801278.
http://dx.doi.org/10.1111/j.1440-1843.20...
; Qiu et al., 2010Qiu, Y. Y., Zhang, X. L., Qin, Y., Yin, K. S., & Zhang, D. P. (2010). Beta(2)-adrenergic receptor haplotype/polymorphisms and asthma susceptibility and clinical phenotype in a Chinese Han population. Allergy and Asthma Proceedings, 31(5), 91-97. http://dx.doi.org/10.2500/aap.2010.31.3371. PMid:20929600.
http://dx.doi.org/10.2500/aap.2010.31.33...
; Chan et al., 2008Chan, I. H., Tang, N. L., Leung, T. F., Huang, W., Lam, Y. Y., Li, C. Y., Wong, C. K., Wong, G. W., & Lam, C. W. (2008). Study of genegene interactions for endophenotypic quantitative traits in Chinese asthmatic children. Allergy, 63(8), 1031-1039. http://dx.doi.org/10.1111/j.1398-9995.2008.01639.x. PMid:18691306.
http://dx.doi.org/10.1111/j.1398-9995.20...
; Wang et al., 2009Wang, J. Y., Liou, Y. H., Wu, Y. J., Hsiao, Y. H., & Wu, L. S. (2009). An association study of 13 SNPs from seven candidate genes with pediatric asthma and a preliminary study for genetic testing by multiple variants in Taiwanese population. Journal of Clinical Immunology, 29(2), 205-209. http://dx.doi.org/10.1007/s10875-008-9256-6. PMid:18931892.
http://dx.doi.org/10.1007/s10875-008-925...
; Pan et al., 2005Pan, Y. P., Zhou, S. L., Kuang, J. L., Rao, W. H. (2005). Study on the relationship between the genetic polymorphisms of β2-adrenergic receptor gene and asthma. Acta academiae Med Jiangxi, 45, 44-47.; Liu et al., 2006Liu, X. H., Cui, L. Y., Li, D. W., Gao, L. X., & Pan, D. S. (2006). Study on β2-adrenergic receptor genetic polymorphisms in asthmatics. Chin J Pract Inter Med, 26, 1526-1529.; Qiu & Yin 2008Qiu, Y. Y., & Yin, K. S. (2008). Relationship between bata2-adrenergic receptor haplotype/polymorphisms and bronchial asthma in the elderly. Shiyong Laonian Yixue, 22, 105-107.; Hua et al., 2008Hua, L., Bao, Y. X., Lv, J., Dong, X. Y., Jin, Z. Q., Tong, Q. T., & Zhang, H. B. (2008). Association of single nucleotide polymorphisms in IL-13 and β2-adrenoreceptor genes with children asthma. J Clin Pediatr, 26, 30-32.; Li et al., 2009Li, H., Xiaoyan, D., Quanhua, L., Jie, L., & Yixiao, B. (2009). Single-nucleotide polymorphisms in genes predisposing to asthma in children of Chinese Han nationality. Journal of Investigational Allergology & Clinical Immunology, 19(5), 391-395. PMid:19862939.; Chen et al., 2014Chen, H. F., Zhang, D. P., Qiu, Y. Y., & Xiao, Y. L. (2014). Association between ADRB2 gene polymorphisms/haplotype and asthma in a Chinese Han population. Acta Univ Med Nanjing, 34, 323-329.; Liu et al., 2014Liu, Z. Q., Jiao, Y., Liu, C. J., Zhang, H. C., & Hu, B. R. (2014). Association between polymorphisms and haplotypes of the beta-2 adrenergic receptor gene and asthma in a Chinese Han population. International Journal of Clinical and Experimental Medicine, 7(10), 3812-3817. PMid:25419437.; Hua et al., 2016Hua, L., Zuo, X. B., Bao, Y. X., Liu, Q. H., Li, J. Y., Lv, J., Fang, D. Z., Lin, Q., Bao, J., & Ji, R. X. (2016). Four-locus gene interaction between IL13, IL4, FCER1B, and ADRB2 for asthma in Chinese Han children. Pediatric Pulmonology, 51(4), 364-371. http://dx.doi.org/10.1002/ppul.23322. PMid:26613553.
http://dx.doi.org/10.1002/ppul.23322...
; Tian et al., 2016Tian, M., Liang, H., Qin, Q. Z., Zhang, W. X., & Zhang, S. S. (2016). ADRB2 polymorphisms in allergic asthma in Han Chinese children. International Forum of Allergy & Rhinology, 6(4), 367-372. http://dx.doi.org/10.1002/alr.21673. PMid:26633084.
http://dx.doi.org/10.1002/alr.21673...
; Guo et al., 2016Guo, X., Zheng, H., Mao, C., Guan, E., & Si, H. (2016). An association and meta-analysis study of 4 SNPs from beta-2 adrenergic receptor (ADRB2) gene with risk of asthma in children. Asian Pacific Journal of Allergy and Immunology, 34(1), 11-20. PMid:26994621.) were used in this report, which met our inclusion criteria. The publication years between 2000 and 2016 were chosen for this meta-analysis. At the end, 6143 asthma cases and 5919 healthy controls for assessing the relation between ADRB2 Arg16Gly polymorphism and asthma risk among Chinese were included in this analysis study (Table 1).

Table 1
Characteristics of studies included in the meta-analysis.

3.2 Meta-analysis

The overall estimated ORs for all studies combined were 0.99, 0.96, 1.02, and 0.95 for contrast of allele (G vs. A), contrast of homozygotes (GG vs. AA), recessive (GG vs. AG+AA) and dominant models (GG+AG vs. AA), respectively (Table 2, Figure 1), these associations were not statistically significant (P>0.05). Next, we performed subgroup analyses according to geographic areas, age group and HWE in controls. Only a borderline significant effect for Southern Chinese was found under the homozygotes genetic model (OR = 0.82, 95%CI = 0.68-1.00, P = 0.046). There was no publication bias for the meta-analyses (t = 1.69, P=0.101; Figures 2 and 3). Sensitivity analysis in Table 2 indicated that the data used in this study were relatively stable and credible based on the fixed-effects model and the random-effects model.

Table 2
Association of the ADRB2 Arg16Gly polymorphism and asthma risk.
Figure 1
Forest plots of all selected studies regarding the association between ADRB2 Arg16Gly polymorphism and asthma risk within the Chinese population under the allele model.
Figure 2
Publication bias assessment of ADRB2 Arg16Gly polymorphism and asthma risk with Begg's funnel plot.
Figure 3
Egger's linear regression for the Begg's funnel plot.

4 Discussion

Many articles had been published to analyze the relation in ADRB2 Arg16Gly polymorphism and asthma, however, no comprehensive exact conclusion was obtained. In a previous study, ADRB2 Arg/Gly16 showed a significant association with asthma in Asian population (Xie et al., 2014Xie, H., Cheng, Y., Huo, Y., Huang, G., & Su, J. (2014). Association between β2-adrenoceptor gene polymorphisms and asthma risk: an updated meta-analysis. PLoS One, 9(7), e101861. http://dx.doi.org/10.1371/journal.pone.0101861. PMid:24992184.
http://dx.doi.org/10.1371/journal.pone.0...
). The subgroup analysis based on the age showed that, compared to the other genotypes, Gly16 had recessive protective functions for children (Thakkinstian et al., 2005Thakkinstian, A., McEvoy, M., Minelli, C., Gibson, P., Hancox, B., Duffy, D., Thompson, J., Hall, I., Kaufman, J., Leung, T. F., Helms, P. J., Hakonarson, H., Halpi, E., Navon, R., & Attia, J. (2005). Systematic review and meta-analysis of the association between {beta}2-adrenoceptor polymorphisms and asthma: a HuGE review. American Journal of Epidemiology, 162(3), 201-211. http://dx.doi.org/10.1093/aje/kwi184. PMid:15987731.
http://dx.doi.org/10.1093/aje/kwi184...
). Individual study could generate diverse results as the variability in region and individual in different populations, or due to the limit of cases. Furthermore, a unique culture and lifestyle from diverse ethnic group resulted in the different genetic trait. To avoid these limits, we performed this study to further survey the relation about ADRB2 Arg16Gly polymorphism and asthma in Chinese populations.

Analyses of 34 publications including 6143 asthma cases and 5919 healthy controls provided the evidence that ADRB2 Arg16Gly polymorphism was not an important risk factor for asthma in Chinese. Subgroup analysis suggested that only a borderline significant effect for southern Chinese was found under the homozygotes genetic model. No association between ADRB2 Arg16Gly polymorphism and the risk of asthma was found in other subgroups. Therefore, this meta-analysis indicated that there may be no connection between ADRB2 Arg16Gly polymorphism and asthma in China. These findings were also found in other meta-analyses, which showed that ADRB2 Arg16Gly gene polymorphism was not related to asthma in the children and general populations (Guo et al, 2016Guo, X., Zheng, H., Mao, C., Guan, E., & Si, H. (2016). An association and meta-analysis study of 4 SNPs from beta-2 adrenergic receptor (ADRB2) gene with risk of asthma in children. Asian Pacific Journal of Allergy and Immunology, 34(1), 11-20. PMid:26994621.; Liang et al., 2014Liang, S. Q., Chen, X. L., Deng, J. M., Wei, X., Gong, C., Chen, Z. R., & Wang, Z. B. (2014). Beta-2 adrenergic receptor (ADRB2) gene polymorphisms and the risk of asthma: a meta-analysis of case-control studies. PLoS One, 9(8), e104488. http://dx.doi.org/10.1371/journal.pone.0104488. PMid:25111792.
http://dx.doi.org/10.1371/journal.pone.0...
; Khan et al., 2018Khan, I., Ul-Haq, Z., Shaheen, A., Zaman, M., Ahmad, N., Abbasi, R., & Siraj, S. (2018). Association of arg16gly and gln27glu, b2-adrenergic receptor gene polymorphism with asthma. A systematic review and meta-analysis of case control studies. JPMA. The Journal of the Pakistan Medical Association, 68(1), 90-97. PMid:29371726.).

Most importantly, ADRB2 Arg16Gly polymorphism may vary greatly between different races, but this study mainly focused on Chinese population. In the meta-analysis, heterogeneity is often observed among genetic association studies. Although subgroup analysis was done according to geographic areas, ages and HWE in controls, the heterogeneity was not effectively decreased. Therefore, other factors may be the potential reasons for their heterogeneity. Additionally, the following deficiencies need to be mentioned: First, significant heterogeneity still existed in the subgroup analysis, thus might introduce some bias. Secondly, we cannot perform some other subgroup analyses such as sex, and asthma phenotype due to the limitation of data. Thirdly, the risks for asthma are multifactorial and complicated, and only genetic variation is often difficult to determine the cause-effect relationships of asthma.

5 Conclusion

This meta-analysis proves that ADRB2 Arg16Gly polymorphism is not related to in development of asthma in China. However, due to some limitations exited in this study, further studies are needed to validate the interactions between ADRB2 Arg16Gly polymorphism and asthma susceptibility based on more information.

  • Practical Application: This meta-analysis proves that ADRB2 Arg16Gly polymorphism is not related to in development of asthma in China.

References

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    » http://dx.doi.org/10.1111/j.1398-9995.2008.01639.x
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  • Cui, L. Y., Liu, X. H., Gao, L. X., & Fan, D. S. (2007). Study on the Association between b2-adrenergic Receptor Genetic polymorphisms and asthma in the population of Inner Mongolia. Chinese journal of Clinical Medicin, 14, 477-481.
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  • Guo, X., Zheng, H., Mao, C., Guan, E., & Si, H. (2016). An association and meta-analysis study of 4 SNPs from beta-2 adrenergic receptor (ADRB2) gene with risk of asthma in children. Asian Pacific Journal of Allergy and Immunology, 34(1), 11-20. PMid:26994621.
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  • Hua, L., Zuo, X. B., Bao, Y. X., Liu, Q. H., Li, J. Y., Lv, J., Fang, D. Z., Lin, Q., Bao, J., & Ji, R. X. (2016). Four-locus gene interaction between IL13, IL4, FCER1B, and ADRB2 for asthma in Chinese Han children. Pediatric Pulmonology, 51(4), 364-371. http://dx.doi.org/10.1002/ppul.23322 PMid:26613553.
    » http://dx.doi.org/10.1002/ppul.23322
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Publication Dates

  • Publication in this collection
    01 Feb 2021
  • Date of issue
    Jul-Sep 2021

History

  • Received
    06 May 2020
  • Accepted
    30 July 2020
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