Journal Article
Research Support, Non-U.S. Gov't
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Polymorphisms in the ADRB2 gene and Graves disease: a case-control study and a meta-analysis of available evidence.

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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