Abstract:
:Thyroid-stimulating hormone (TSH) is a sensitive indicator of thyroid function. High and low TSH levels reflect hypothyroidism and hyperthyroidism, respectively. Even within the normal range, small differences in TSH levels, on the order of 0.5-1.0 mU/l, are associated with significant differences in blood pressure, BMI, dyslipidemia, risk of atrial fibrillation and atherosclerosis. Most of the variance in TSH levels is thought to be genetically influenced. We conducted a genome-wide association study of TSH levels in 1346 Chinese Han individuals. In the replication study, we genotyped four candidate SNPs with the top association signals in an independent isolated Chinese She cohort (n = 3235). We identified a novel serum TSH susceptibility locus within XKR4 at 8q12.1 (rs2622590, Pcombined = 2.21 × 10(-10)), and we confirmed two previously reported TSH susceptibility loci near FOXE1 at 9q22.33 and near CAPZB at 1p36.13, respectively. The rs2622590_T allele at XKR4 and the rs925489_C allele near FOXE1 were correlated with low TSH levels and were found to be nominally associated to patients with papillary thyroid carcinoma (PTC) (OR = 1.41, P= 0.014 for rs2622590_T, and OR = 1.61, P= 0.030 for rs925489_C). The rs2622590 and rs925489 genotypes were also correlated with the expression levels of FOXE1 and XKR4, respectively, in PTC tissues (P = 2.41 × 10(-4) and P= 0.02). Our findings suggest that the SNPs in XKR4 and near FOXE1 are involved in the regulation of TSH levels.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Zhan M,Chen G,Pan CM,Gu ZH,Zhao SX,Liu W,Wang HN,Ye XP,Xie HJ,Yu SS,Liang J,Gao GQ,Yuan GY,Zhang XM,Zuo CL,Su B,Huang W,Ning G,Chen SJ,Chen JL,Song HD,China Consortium for Genetics of Autoimmune Thyroid Disease.doi
10.1093/hmg/ddu250subject
Has Abstractpub_date
2014-10-15 00:00:00pages
5505-17issue
20eissn
0964-6906issn
1460-2083pii
ddu250journal_volume
23pub_type
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