A Case-Control Study of the Relationship Between Genetic Polymorphism and Cretinism in Xinjiang

Abstract

Jia Huang,1,2,* Haiyan Wu,2,* Guiqiang Zhao,3 Yan Ma,1 Yunping An,4 Li Sun,5 Fuye Li,1 Shengling Wang2 1Department of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, 830054, People’s Republic of China; 2Division of Endemic Disease Prevention, Xinjiang Uygur Autonomous Region Center for Disease Control and Prevention, Urumqi, Xinjiang, 830002, People’s Republic of China; 3Infection Management Department, Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University, Urumqi, Xinjiang, 830000, People’s Republic of China; 4Kashgar District Center for Disease Control and Prevention, Kashgar, Xinjiang, 844000, People’s Republic of China; 5Ingisha County Center for Disease Control and Prevention, Kashgar, Xinjiang, 844500, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shengling Wang, Department of Division of Endemic Disease Prevention, Center for Disease Control and Prevention of Xinjiang Uighur Autonomous Region, No. 380 of Jianquan Road, Urumqi, Xinjiang, 830002, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected] Fuye Li, Department of Public Health, Xinjiang Medical University, No. 393 Xinyi Road, Urumqi, Xinjiang, 830054, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]: Cretinism is a subtype of congenital hypothyroidism, an endocrine disorder resulting from inadequate thyroid hormone production or receptor deficiency. Genetic abnormalities play a major role in the development of thyroid dysfunction.Methods: We recruited 183 participants with cretinism and 119 healthy participants from the Xinjiang Uyghur Autonomous Region and randomly selected 29 tag single nucleotide polymorphisms (tSNPs) in TSHB, PAX8, TPO, NKX2-5, and TSHR in all participants. We compared genotype and allele frequencies between cases and controls utilizing the chi-squared test, logistic regression analysis, and haplotype analysis.Results: Using the chi-squared test, a single SNP was found to be associated with cretinism (recessive model: rs3754363, OR = 0.46, 95% CI = 0.27– 0.80, P = 0.00519; genotype model: P = 0.01677). We stratified neurological, myxedematous, and mixed type and determined that another SNP was associated with a higher risk when comparing myxedematous type to the neurological type (rs2277923).Conclusion: rs3754363 has a statistically significant protective effect on people with cretinism, while rs2277923 may play a greater role in promoting the development of neurocretinism.Keywords: chi-squared test, cretinism, NKX2-5, SNPs

Keywords

• chi-squared test
• cretinism
• nkx2-5
• snps