Polymorphism as Biomarker Analysis of Genes TSHR, DIO1, FOXE1, and CAPZB in Hypothyroidism Patients.

Objective: The present research was done to explore the possible association of TSHR (rs1991517, rs12050077), DIO1 (rs2235544), FOXE1 (rs925489), and CAPZB (rs10917469) gene variants in hypothyroidism patients.

Design & methods: This study included 600 participants with hypothyroidism and a control. Genomic DNA was extracted from whole blood and amplified using polymerase chain reaction (PCR).

Results: The Homozygous genotype (CC) of SNP rs1991517 of the TSHR gene exhibited a significant association with hypothyroidism by 2-fold more risk of hypothyroidism. In comparison, in the combined genotype model, similar results were obtained with 2-fold more risk of hypothyroidism. In the rs12050077 variant of the TSHR gene, statistically significant results were observed with a 2-fold higher risk of hypothyroidism by homozygous mutant (AA), while a significant association with decreased risk of hypothyroidism was observed in heterozygous (GA). Its joint genotype model (GA+AA) showed a substantial decrease in the risk and played a protective role. In the DIO1 gene, a heterozygous mutant genotype (AC) of variant rs2235544, a significant association with 3-fold increased the risk of hypothyroidism was observed, and homozygous mutant genotype (CC) of the same SNP rs2235544 also showed significant association by decreasing the risk of hypothyroidism. In SNP rs925489 of gene FOXE1, heterozygous (CT) showed a significant association with hypothyroidism. joint genotype model of rs925489 showed a crucial significant association with hypothyroidism. In rs10917469 SNP of CAPZB gene in heterozygous mutant (AG), a significant association was observed but with a decreased risk of hypothyroidism. The joint genotype model of rs10917469 shows a significant association with hypothyroidism.

Conclusions: Association study of TSHR polymorphism (rs1991517, rs12050077), DIO1 polymorphism rs2235544, FOXE1 polymorphism rs925489, and CAPZB polymorphism rs10917469 with hypothyroidism showed that rs2235544 of DIO1 gene are associated with increasing risk of hypothyroidism.