Objective:To explore the correlation between rs231775 polymorphism of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) gene and autoimmune thyroid disease (AITD) of Uygur in Xinjiang Uygur Autonomous Region.Methods:A total of 382 Uygur patients with AITD [including 328 Hashimoto's thyroiditis (HT) patients and 54 Graves' disease (GD) patients] diagnosed in the People's Hospital of Xinjiang Uygur Autonomous Region from January 2017 to December 2018 were selected as the case group, and 383 Uygur health physical examiners in the same period were selected as the control group. The whole blood genomic DNA of the study subjects was extracted, and the Sequenom-mass spectrometry analysis platform was used to determine the genotyping of CTLA4 gene single nucleotide polymorphism (SNP) locus rs231775 and analyze the genetic model, and the correlation between rs231775 polymorphism and AITD under different genetic models was compared. The logistic regression analysis model was used to analyze the influencing factors of AITD. And the thyroid function index of different genotype population was compared.Results:In the case group and the control group, the differences of CTLA4 gene rs231775 alleles (A: 41.88%, 49.35%; G: 58.12%, 50.65%) and genotype frequencies (AA: 17.80%, 23.24%; AG: 48.17%, 52.22%; GG: 34.03%, 24.54%) were statistically significant (χ 2=8.586, 9.260, P < 0.05). Compared with the control group, the genotype frequency of rs231775 in HT group, the alleles and genotype frequencies of rs231775 in GD group were significantly different (χ 2=5.997, 11.130, 10.210, P < 0.05). Under the additive and dominant models, the CTLA4 gene rs231775 was correlated with AITD [odds ratio ( OR)=0.67, 0.55, 0.63] and HT ( OR=0.69, 0.62, 0.67, P < 0.05); and correlated with GD under the additive, dominant and recessive genetic models ( OR=0.53, 0.23, 0.44, 0.34, P < 0.05). The logistic regression analysis showed that genotype, gender, age, thyroid stimulating hormone (TSH) and free thyroxine (FT 4) were independent influencing factors of AITD ( P < 0.05). Among all the subjects, the level of thyroglobulin antibody(TgAb) in the population with the recessive genotype (GG) at the rs231775 of the CTLA4 gene was higher than that in the dominant genotype (AA+AG) population ( P < 0.05). Conclusion:The CTLA4 gene rs231775 polymorphism is significantly related to AITD of Uygur in Xinjiang Uygur Autonomous Region, and the level of TgAb in GG genotype is higher than that in other genotypes.

Objective:To investigate the correlation of multiple single nucleotide polymorphisms(SNPs)of thyroid peroxidase(TPO)and thyroglobulin(Tg)genes with Hashimoto′s thyroiditis(HT).Methods:Based on the gene mutation sites obtained from the second-generation sequencing of the target region of the previous autoimmune thyroid disease cases in our research group, the representative sites were selected for confirming in the expanded samples. A total of 301 Uyghur patients with HT and 383 controls were selected to determine the genotypes of representative SNPs(rs4927631, rs2071400, rs2071403, rs2403883, rs4236899, rs4736434, rs180195)using MassArry Sequenom platform. Correlation analysis and linkage analysis were performed with SPSS 21.0 software.Results:(1)The SNP rs4927631 gene frequency and genotype of TPO gene were significantly different between the case and control groups. The SNP rs2071403 gene frequency of TPO gene revealed statistically different between the case and control groups.(2)With analysis under different genetic models, the rs4927631 and rs2071403 of TPO gene were associated with HT under the additive model(AA/GG)and dominant model( P<0.05). The rs180195 of Tg gene was associated with HT in a recessive model( P<0.05). (3)All subjects were grouped according to the dominant genotype(AA+ GA)and recessive genotype(GG)of the TPO gene rs2071403, and mean age, gender distribution, proportion of those with higher TSH, and lower FT 4 were compared between two groups. Only thyroid peroxidase antibody(TPOAb) level displayed a statistical difference( P<0.05). This was the case for the patients with HT after grouped according to the above method( P<0.05). Conclusion:The rs4927631 and rs2071403 loci of TPO gene are associated with the pathogenesis of HT in Xinjiang Uygur.

Objective To investigate the relationship between thyrotropin(TSH)and urine iodine in pregnant women of Han and Uygur ethnic groups in People′s Hospital of Xinjiang Uygur Autonomous Region. Methods A total of 1568 pregnant who completed screening of TSH and urine iodine in People′s Hospital of Xinjiang Uygur Autonomous Region hospital from August 2014 to December 2017 were included in the study, 956 cases were Han and the other 612 were Uygur. Basic clinical data, serum TSH, thyroid peroxidase autoantibody (TPOAb), and urine iodine levels were retrospectively analyzed. Results (1) General results:The median urine iodine level was 162.6μg/L(53.4-539.3μg/L), and the distribution of urine iodine classification was iodine deficiency 42.9％(672/1568), iodine appropriate 36.7％(576/1568), iodine slightly high 17.1％(268/1568)and iodine excess 3.3％(52/1568)respectively.(2)The median urine iodine levels of Han and Uygur pregnant women were 169.1μg/L(54.6-583.4μg/L)and 156.3μg/L (53.1-539.3μg/L)respectively, and the difference was statistically significant(P<0.05).The distribution of urine iodine status in pregnancy between Han and Uygur was significantly different, which were 40.9％(391/956)vs. 45.9％(281/612)in iodine deficiency, 35.4％(338/956)vs. 38.9％(238/612)in iodine appropriate, 20.2％(193/956) vs. 12.3％(75/612) in iodine slightly high and 3.6％(34/956) vs. 2.9％(18/612)in iodine excess.(3)High serum TSH level proportion was significantly higher in Uygur ethnic group, early pregnancy, thyroid peroxidase antibody positive and anti-thyroglobulin antibody positive group when compared with Han, late pregnancy, thyroid peroxidase antibody negative and anti-thyroglobulin antibody negative groups (all P<0.05). There were no significant differences in different age groups and iodine nutrition groups(P>0.05).(4)There was no correlation between urinary iodine and TSH levels in all pregnant women(P>0.05),neither in Han or Uygur group. When further stratified by gestational age, age, and antibody level, there was a positive correlation between urine iodine and serum TSH level in Han pregnant women>30 years old(P<0.05), and there was a negative correlation in the third trimester in Uygur (P<0.05). When serum antibody level, gestational week and age were controlled. There was no correlation between urine iodine and serum TSH level in neither group. Conclusions (1)In Han and Uygur pregnant women, the median urine iodine level and the distribution of urine iodine classification between two ethnic groups are significantly different.(2)The correlation between urine iodine and serum TSH is not identified in Han or Uygur pregnant women.

Objective To establish a reference range for specific thyroid function during pregnancy and to explore the influencing factors of hypothyroxinemia during pregnancy.Methods A retrospective analysis of 2 996 cases of thyroid function in the pregnant women who were with single pregnancy and without thyroid diseases and family history of those diseases.Results (1) Establish a unified reference range for specific thyroid function during pregnancy;the early,middle,and late trimesters thyrotropin (TSH) ranges were 0.02-6.39,0.16-6.23,0.64-6.59 mU/L,respectively,while free thyroxine (FT4) ranges were 11.32-23.00,9.39-18.92,8.54-16.73 pmol/L respectively.The specific reference ranges of Han and Uygur pregnant women were established separately.There was no difference in the detection rates of various thyroid diseases when using their respective reference ranges and the unified reference range of the hospital (P ＞ 0.05).(2) The detection rate of various thyroid diseases (except subclinical hyperthyroidism) of our subjects with China guideline reference range was significantly higher than the reference range with the hospital (P＜0.05).(3) The detection rates of hypothyroxinemia in all pregnant women with FT4 cut points of P2.5 and P5 were 4.3％ and 7.4％,respectively,of which the Han population was 4.3％ and 7.1％,respectively,and the Uygur population was 4.3％ and 7.9％,respectively.(4) Comparing the mean age,gestational age,median urine iodine,and thyroid antibody positive rate between the hypothyroxinemia group and the control group,only the mean age and gestational age were different (P＜0.05);Logistic binary regression analysis showed that age was the risk factor for hypothyroxinemia during pregnancy (OR =1.035,95％ CI 1.006-1.066,P ＜ 0.05).Conclusions The Han and Uygur pregnant women in this area both can use the thyroid reference range of our hospital during pregnancy.The establishment of thyroid reference range may avoid over-diagnosis of thyroid disease during pregnancy.Age is a possible influencing factor of hypothyroxinemia during pregnancy.

Objective:To observe the dynamic changes of thyroid hormone levels and thyroid autoimmune antibodies in pregnant women in Xinjiang Uygur Autonomous Region during pregnancy, and to investigate the significance of repeated screening of thyroid function in different gestational ages.Methods:A retrospective study was carried out of pregnant women who completed thyroid function screening in Clinic, People's Hospital of Xinjiang Uygur Autonomous Region from January 2015 to December 2017, and the test results of thyroid stimulating hormone (TSH), free thyroxine (FT 4), free triiodothyronine (FT 3), thyroid peroxidase antibody (TPOAb), and anti-thyroglobulin antibody (TGAb) were collected and analyzed of their changes during pregnancy. Pregnant women were divided into 2 different gestational age groups by the age limit of 30, the changes of thyroid dysfunction rate with pregnancy were analyzed, and the clinical significance of repeated screening in different pregnancy stages was discussed. Results:Changes of thyroid-related indicators with pregnancy: first, second, and third trimesters were 404,725, and 767 cases, respectively; TSH level in the third trimester (2.76 mU/L) was significantly higher than those in the first and second trimesters (2.55, 2.36 mU/L, P < 0.05), there was no significant difference between the first trimester and the second trimester ( P > 0.05); the FT 4 and FT 3 levels decreased gradually with pregnancy ( P < 0.05); the positive rate of TPOAb was significantly higher in the first and second trimesters than that in the third trimester ( P < 0.05), there was no significant difference between the first trimester and the second trimester ( P > 0.05); the positive rate of TGAb decreased gradually with pregnancy ( P < 0.05). Comparison of abnormal rate of TSH in different gestational ages: the first, second, and third trimesters were 352, 664, 735 cases, respectively; the abnormal rate of TSH in the overall study was statistically significant at different stages of pregnancy (χ 2=31.627, P < 0.05), the first trimester was significantly higher those in the second and third trimesters ( P < 0.05). In pregnant women aged ≥30 years old, the abnormal rate of TSH in the first trimester was significantly higher than those in the second and third trimesters ( P < 0.05); in pregnant women aged < 30 years old, the abnormal rate of TSH in the first trimester was significantly higher than that in the third trimester ( P < 0.05). There were no significant differences in the abnormal rate of TSH in the first, second, and third trimesters between the < 30 years old group and ≥30 years old group ( P > 0.05). Comparison of abnormal rate of FT 4 in different gestational ages: there were no significant differences in the FT 4 abnormal rate among different pregnancy groups in the overall, < 30, ≥30 years old groups (P > 0.05). In early pregnancy, the abnormal rate of FT 4 in the ≥30 years old group was higher than that in the < 30 years old group ( P < 0.05); in second and third trimesters, there were no significant differences between the two age groups ( P > 0.05). Conclusions:Screening for thyroid function in the first trimester of pregnancy is important for women of different ages. Except for women with abnormal thyroid function who have not been treated during the first trimester, the rest may not need to be screened again. Pregnant women aged ≥30 years old may have a higher risk of thyroid dysfunction than those < 30 years old.