In total, 28 SNPs revealed association with GD (</span>P < 0.05), with strongest SNP associations at rs179247 (chi(2) = 32.45, P = 8.90 x 10(-8), OR = 1.53, 95% CI = 1.32-1.78) and rs12101255 (chi(2) = 30.91, P = 1.95 x 10(-7), OR = 1.55, 95% CI = 1.33-1.81), both located in intron 1 of the TSHR.
Seven different recurrent mutations [p.G488R (n=13), p.A649E (n=3), p.R885Q (n=3), p.I1080T (n=2), and p.A1206T (n=2) in DUOX2; p.Y138X (n=9) in DUOXA2; and p.R450H (n=5) in TSHR) were identified as the mutations underlying CH.
Seven different recurrent mutations [p.G488R (n=13), p.A649E (n=3), p.R885Q (n=3), p.I1080T (n=2), and p.A1206T (n=2) in DUOX2; p.Y138X (n=9) in DUOXA2; and p.R450H (n=5) in TSHR) were identified as the mutations underlying CH.
He needed levothyroxine (l-T4) replacement therapy to keep serum TSH levels within normal limits; l-T4 dose of 2.01-2.65 μg/kg/day corresponded to the dose taken by children homozygous for R450H-TSHR and by children with permanent congenital hypothyroidism.
Frequency and clinical implication of the R450H mutation in the thyrotropin receptor gene in the Japanese population detected by Smart Amplification Process 2.
Clinical significance of heterozygous carriers associated with compensated hypothyroidism in R450H, a common inactivating mutation of the thyrotropin receptor gene in Japanese.
The TSHR alleles rs179247-G, rs12101261-C, and rs4903964-G were negatively correlated with GD, whereas the rs2284722-A and rs17111394-C alleles were positively correlated with GD.
With respect to haplotypes based on SNPs at the TSHR rs2300525 and rs17111394 loci, the CC haplotype was positively correlated with GD risk (OR = 1.32, 95%CI = 1.08-1.60, <i>P</i> = 0.006).