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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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Meta-analysis of the association between rs1042714 and GD measured by allele frequency data. OR (black squares) and 95% CI (bar) are shown for each study. The pooled ORs and their 95% CIs are represented by the shaded diamonds. Summary ORs are given for each ethnic group as well as all groups combined. The symbol n indicates the total number of C alleles, and N indicates the total number of C plus G alleles. A) DerSimonian-Laird OR meta-analysis (random effects) of the three studies; B) Mantel-Haenszel OR meta-analysis (fixed effects) of the two European studies.
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Figure 2: Meta-analysis of the association between rs1042714 and GD measured by allele frequency data. OR (black squares) and 95% CI (bar) are shown for each study. The pooled ORs and their 95% CIs are represented by the shaded diamonds. Summary ORs are given for each ethnic group as well as all groups combined. The symbol n indicates the total number of C alleles, and N indicates the total number of C plus G alleles. A) DerSimonian-Laird OR meta-analysis (random effects) of the three studies; B) Mantel-Haenszel OR meta-analysis (fixed effects) of the two European studies.

Mentions: A meta-analysis for rs1042714 was conducted combining the initial findings from the Polish populations, the data set from the study of WTCCC et al. and the result of present study, including a total of 1,728 GD patients and 2,491 control samples. The forest plots for the allele model are shown in Figure 2. The p-value for Q-test is just above the significance level (P = 0.12, Figure 2A), whereas the I2 statistic suggested there was significant heterogeneity among the studies (I2 = 53.1%, Figure 2A). Since only three studies were included in our meta-analysis, we chose the result of I2 statistic as measurement of heterogeneity. Then the pooled OR was calculated by random effects approaches using DerSimonian and Laird methods[20]. The pooled OR was 1.13 but the confidence interval spanned unity (95% CI, 0.95 to 1.36), which indicated the combined data did not show significant association for rs1042714 with GD. A sensitivity analysis showed that the present study in Chinese population was the main cause of the heterogeneity. When only the two European studies (including 1300 cases and 1801 controls) were combined, the heterogeneity was no longer significant (I2 = 5.9%, Figure 2B), and the result demonstrated significant association by fixed effect (OR = 1.18, 95% CI, 1.06 to 1.32; P = 0.002, Figure 2B).


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)

Meta-analysis of the association between rs1042714 and GD measured by allele frequency data. OR (black squares) and 95% CI (bar) are shown for each study. The pooled ORs and their 95% CIs are represented by the shaded diamonds. Summary ORs are given for each ethnic group as well as all groups combined. The symbol n indicates the total number of C alleles, and N indicates the total number of C plus G alleles. A) DerSimonian-Laird OR meta-analysis (random effects) of the three studies; B) Mantel-Haenszel OR meta-analysis (fixed effects) of the two European studies.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Meta-analysis of the association between rs1042714 and GD measured by allele frequency data. OR (black squares) and 95% CI (bar) are shown for each study. The pooled ORs and their 95% CIs are represented by the shaded diamonds. Summary ORs are given for each ethnic group as well as all groups combined. The symbol n indicates the total number of C alleles, and N indicates the total number of C plus G alleles. A) DerSimonian-Laird OR meta-analysis (random effects) of the three studies; B) Mantel-Haenszel OR meta-analysis (fixed effects) of the two European studies.
Mentions: A meta-analysis for rs1042714 was conducted combining the initial findings from the Polish populations, the data set from the study of WTCCC et al. and the result of present study, including a total of 1,728 GD patients and 2,491 control samples. The forest plots for the allele model are shown in Figure 2. The p-value for Q-test is just above the significance level (P = 0.12, Figure 2A), whereas the I2 statistic suggested there was significant heterogeneity among the studies (I2 = 53.1%, Figure 2A). Since only three studies were included in our meta-analysis, we chose the result of I2 statistic as measurement of heterogeneity. Then the pooled OR was calculated by random effects approaches using DerSimonian and Laird methods[20]. The pooled OR was 1.13 but the confidence interval spanned unity (95% CI, 0.95 to 1.36), which indicated the combined data did not show significant association for rs1042714 with GD. A sensitivity analysis showed that the present study in Chinese population was the main cause of the heterogeneity. When only the two European studies (including 1300 cases and 1801 controls) were combined, the heterogeneity was no longer significant (I2 = 5.9%, Figure 2B), and the result demonstrated significant association by fixed effect (OR = 1.18, 95% CI, 1.06 to 1.32; P = 0.002, Figure 2B).

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