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Polymorphisms in the ADRB2 gene and Graves disease: a case-control study and a meta-analysis of available evidence.

Chu X, Dong Y, Shen M, Sun L, Dong C, Wang Y, Wang B, Zhang K, Hua Q, Xu S, Huang W - BMC Med. Genet. (2009)

Bottom Line: However, significant association was found from the combined data of Caucasian population with a fixed effects model (OR = 1.18, 95% CI, 1.06 to 1.32; P = 0.002; I2 = 5.9%).Our study indicated that the ADRB2 gene did not exert a substantial influence on GD susceptibility in Han Chinese population, but contributed to a detectable GD risk in Caucasian population.This inconsistency resulted largely from between-ethnicity heterogeneity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China. chux@chgc.sh.cn

ABSTRACT

Background: The beta-2-Adrenergic receptor (ADRB2) gene on chromosome 5q33.1 is an important immunoregulatory factor. We and others have previously implicated chromosomal region 5q31-33 for contribution to the genetic susceptibility to Graves disease (GD) in East-Asian populations. Two recent studies showed associations between the single nucleotide polymorphism (SNP) rs1042714 in the ADRB2 gene and GD. In this study, we aimed to fully investigate whether the ADRB2 gene conferred susceptibility to GD in Chinese population, and to perform a meta-analysis of association between ADRB2 and GD.

Methods: Approximately 1 kb upstream the transcription start site and the entire coding regions of the ADRB2 gene were resequenced in 48 Han Chinese individuals to determine the linkage disequilibrium (LD) patterns. Tag SNPs were selected and genotyped in a case-control collection of 1,118 South Han Chinese subjects, which included 428 GD patients and 690 control subjects. A meta-analysis was performed with the data obtained in the present samples and those available from prior studies.

Results: Fifteen SNPs in the ADRB2 gene were identified by resequencing and one SNP was novel. Ten tag SNPs were investigated further to assess association of ADRB2 in the case-control collection. Neither individual tag SNP nor haplotypes showed association with GD in Han Chinese population (P > 0.05). Our meta-analysis of the ADRB2 SNP rs1042714 measured heterogeneity between the ethnic groups (I2 = 53.1%) and no association to GD was observed in the overall three studies with a random effects model (OR = 1.13, 95% CI, 0.95 to 1.36; P = 0.18). However, significant association was found from the combined data of Caucasian population with a fixed effects model (OR = 1.18, 95% CI, 1.06 to 1.32; P = 0.002; I2 = 5.9%).

Conclusion: Our study indicated that the ADRB2 gene did not exert a substantial influence on GD susceptibility in Han Chinese population, but contributed to a detectable GD risk in Caucasian population. This inconsistency resulted largely from between-ethnicity heterogeneity.

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Linkage disequilibrium (LD) plots of the fifteen SNPs in ADRB2 identified from 48 subjects. We constructed the plots with the Haploview program [15], and r2 (×100) values were depicted in the diamonds. Blocks were determined using the default method of Gabriel et al [16].
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Figure 1: Linkage disequilibrium (LD) plots of the fifteen SNPs in ADRB2 identified from 48 subjects. We constructed the plots with the Haploview program [15], and r2 (×100) values were depicted in the diamonds. Blocks were determined using the default method of Gabriel et al [16].

Mentions: Fifteen polymorphisms were identified through the resequencing of ADRB2 for 48 individuals (Table 1), all of which were SNPs; one SNP (-332) located at position -332 upstream from the ADRB2 transcription initiation site was novel when compared with dbSNP Build 128. The nonsynonymous SNP rs1800888 at nt 491 (+491 C→T, 164 Thr→Ile) in the coding region was found not to be polymorphic in these 48 Chinese individuals. Among the fifteen SNPs, twelve SNPs had minor allele frequencies (MAF) great than 5% (Table 1), with frequencies ranging from 5.2% (rs1042711, rs1801704 and rs1042714) to 38.9% (rs1042719). The frequencies of the fifteen SNPs in 48 individuals were in Hardy-Weinberg equilibrium (P > 0.05, Table 1). The linkage disequilibrium (LD) structure among the SNPs was examined by program Haploview 4.0 (Figure 1). The LD between rs11959427 and rs1042714 (D' = 1, r2 = 0.82) is similar to a previous report by Japanese researchers [6], but much stronger than that in the Polish study [7].


Polymorphisms in the ADRB2 gene and Graves disease: a case-control study and a meta-analysis of available evidence.

Chu X, Dong Y, Shen M, Sun L, Dong C, Wang Y, Wang B, Zhang K, Hua Q, Xu S, Huang W - BMC Med. Genet. (2009)

Linkage disequilibrium (LD) plots of the fifteen SNPs in ADRB2 identified from 48 subjects. We constructed the plots with the Haploview program [15], and r2 (×100) values were depicted in the diamonds. Blocks were determined using the default method of Gabriel et al [16].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2666670&req=5

Figure 1: Linkage disequilibrium (LD) plots of the fifteen SNPs in ADRB2 identified from 48 subjects. We constructed the plots with the Haploview program [15], and r2 (×100) values were depicted in the diamonds. Blocks were determined using the default method of Gabriel et al [16].
Mentions: Fifteen polymorphisms were identified through the resequencing of ADRB2 for 48 individuals (Table 1), all of which were SNPs; one SNP (-332) located at position -332 upstream from the ADRB2 transcription initiation site was novel when compared with dbSNP Build 128. The nonsynonymous SNP rs1800888 at nt 491 (+491 C→T, 164 Thr→Ile) in the coding region was found not to be polymorphic in these 48 Chinese individuals. Among the fifteen SNPs, twelve SNPs had minor allele frequencies (MAF) great than 5% (Table 1), with frequencies ranging from 5.2% (rs1042711, rs1801704 and rs1042714) to 38.9% (rs1042719). The frequencies of the fifteen SNPs in 48 individuals were in Hardy-Weinberg equilibrium (P > 0.05, Table 1). The linkage disequilibrium (LD) structure among the SNPs was examined by program Haploview 4.0 (Figure 1). The LD between rs11959427 and rs1042714 (D' = 1, r2 = 0.82) is similar to a previous report by Japanese researchers [6], but much stronger than that in the Polish study [7].

Bottom Line: However, significant association was found from the combined data of Caucasian population with a fixed effects model (OR = 1.18, 95% CI, 1.06 to 1.32; P = 0.002; I2 = 5.9%).Our study indicated that the ADRB2 gene did not exert a substantial influence on GD susceptibility in Han Chinese population, but contributed to a detectable GD risk in Caucasian population.This inconsistency resulted largely from between-ethnicity heterogeneity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China. chux@chgc.sh.cn

ABSTRACT

Background: The beta-2-Adrenergic receptor (ADRB2) gene on chromosome 5q33.1 is an important immunoregulatory factor. We and others have previously implicated chromosomal region 5q31-33 for contribution to the genetic susceptibility to Graves disease (GD) in East-Asian populations. Two recent studies showed associations between the single nucleotide polymorphism (SNP) rs1042714 in the ADRB2 gene and GD. In this study, we aimed to fully investigate whether the ADRB2 gene conferred susceptibility to GD in Chinese population, and to perform a meta-analysis of association between ADRB2 and GD.

Methods: Approximately 1 kb upstream the transcription start site and the entire coding regions of the ADRB2 gene were resequenced in 48 Han Chinese individuals to determine the linkage disequilibrium (LD) patterns. Tag SNPs were selected and genotyped in a case-control collection of 1,118 South Han Chinese subjects, which included 428 GD patients and 690 control subjects. A meta-analysis was performed with the data obtained in the present samples and those available from prior studies.

Results: Fifteen SNPs in the ADRB2 gene were identified by resequencing and one SNP was novel. Ten tag SNPs were investigated further to assess association of ADRB2 in the case-control collection. Neither individual tag SNP nor haplotypes showed association with GD in Han Chinese population (P > 0.05). Our meta-analysis of the ADRB2 SNP rs1042714 measured heterogeneity between the ethnic groups (I2 = 53.1%) and no association to GD was observed in the overall three studies with a random effects model (OR = 1.13, 95% CI, 0.95 to 1.36; P = 0.18). However, significant association was found from the combined data of Caucasian population with a fixed effects model (OR = 1.18, 95% CI, 1.06 to 1.32; P = 0.002; I2 = 5.9%).

Conclusion: Our study indicated that the ADRB2 gene did not exert a substantial influence on GD susceptibility in Han Chinese population, but contributed to a detectable GD risk in Caucasian population. This inconsistency resulted largely from between-ethnicity heterogeneity.

Show MeSH
Related in: MedlinePlus