Association Between TAB2 Gene Polymorphisms and Susceptibility to Cryptorchidism in Han Chinese Population in Southwest China

SU Min, LI Zhi-long, SONG Ya-ping, WANG Yan-yun, ZHOU Bin, LI Qin

Abstract

To conduct preliminary investigation into the correlation between transforming growth factor beta-activated protein kinase 1-binding protein 2 (TAB2) gene and the incidence of cryptorchidism in Han Chinese population in Southwest China.  Methods  A total of 259 patients with cryptorchidism and 355 healthy controls from Southwest China were enrolled for the study. Polymerase chain reaction-restriction fragment length polymorphism method was used to analyze the genotype of the 3 tag single nucleotide polymorphisms (SNPs) of TAB2 gene, i.e., rs237028, rs521845 and rs652921. The Chi-square test was used to analyze the relationship between the genotype frequency of the three tag SNPs and the incidence of cryptorchidism.  Results  The distribution of the 3 tag SNPs’ alleles and genotypes were in agreement with the Hardy-Weinberg equilibrium, and the genotype results of polymerase chain reaction-restriction fragment length polymorphism assay were consistent with those of Sanger sequencing. The frequency of the G allele at TAB 2 rs237028 was significantly higher in the cryptorchidism group than that in the control group (30.9% vs. 25.6%, P=0.04, OR=1.31, 95% CI: 1.01-1.70). In the dominant model, the risk of cryptorchidism was significantly higher in AG/GG genotype carriers (P=0.006, OR=1.57, 95% CI: 1.14-2.17). In the cryptorchidism group, the TC/CC genotype frequency of the rs652921 locus were significantly higher than that of the control group (75.3% vs. 67.0%, P=0.03, OR=1.50, 95% CI: 1.05-2.14). Correlation between rs521845 and susceptibility to cryptorchidism was not observed in the Han Chinese population.  Conclusion  The AG/GG genotype of rs237028 locus and the TC/CC genotype of rs652921 locus of the TAB2 gene may be associated with increased risks of cryptorchidism in Han Chinese population in southwest China.

 

Keywords: Cryptorchidism, TAB2 gene, Single nucleotide polymorphism, Polymerase chain reaction, Susceptibility

 

Full Text:

PDF


References


FAN Y S， HU Y J， YANG W X. TGF-β superfamily: How does it regulate testis development? Mol Biol Rep，2012，39(4): 4727–4741.

CHEN P， PU Y， ZHOU B， et al. Association between two single nucleotide polymorphisms of interleukin-27 gene and increased cryptorchidism risk. Andrologia，2016，48(2): 193–197.

ELDER J S. Surgical management of the undescended testis: Recent advances and controversies. Eur J Pediatr Surg，2016，26(5): 418–426.

GOEL P， RAWAT J D， WAKHLU A， et al. Undescended testicle: An update on fertility in cryptorchid men. Indian J Med Res，2015，141(2): 163–171.

KAFTANOVSKAYA E M， NEUKIRCHNER G， HUFF V， et al. Left-sided cryptorchidism in mice with Wilms' tumour 1 gene deletion in gubernaculum testis. J Pathol，2013，230(1): 39–47.

WEISS K， APPLEGATE C， WANG T， et al. Familial TAB2 microdeletion and congenital heart defects including unusual valve dysplasia and tetralogy of fallot. Am J Med Genet A，2015，167a(11): 2702–2706.

CHENG A， NEUFELD-KAISER W， BYERS P H， et al. 6q25.1 (TAB2) microdeletion is a risk factor for hypoplastic left heart: A case report that expands the phenotype. BMC Cardiovasc Disord，2020，20(1): 137.

ENGWERDA A， LEENDERS E， FRENTZ B， et al. TAB2 deletions and variants cause a highly recognisable syndrome with mitral valve disease, cardiomyopathy, short stature and hypermobility. Eur J Hum Genet， 2021，29(11): 1669–1676.

HANSON J， BREZAVAR D， HUGHES S， et al. TAB2 variants cause cardiovascular heart disease, connective tissue disorder, and developmental delay. Clin Genet，2022，101(2): 214–220.

XU Z， TAYLOR J A. SNPinfo: Integrating GWAS and candidate gene information into functional SNP selection for genetic association studies. Nucleic Acids Res， 2009， 37(Suppl 2): W600−W605[2022-01-14]. https://doi.org/10.1093/nar/gkp290.

UNTERGASSER A， CUTCUTACHE I， KORESSAAR T， et al. Primer3--new capabilities and interfaces. Nucleic Acids Res， 2012， 40(15): e115[2022-01-14]. https://doi.org/10.1093/nar/gks596.

DUPONT W D， PLUMMER W D， Jr. Power and sample size calculations for studies involving linear regression. Control Clin Trials， 1998，19(6): 589–601.

ZHANG D， MA M， PU Y， et al. Genetic association between IL-21 polymorphisms and cryptorchidism in a Chinese Han population. Genet Test Mol Biomarkers，2016，20(5): 261–264.

VIRTANEN H E， BJERKNES R， CORTES D， et al. Cryptorchidism: classification, prevalence and long-term consequences. Acta Paediatr， 2007，96(5): 611–616.

HUANG X， SHEN C， ZHANG Y， et al. Associations between TAB2 gene polymorphisms and epithelial ovarian cancer in a Chinese Population. Dis Markers， 2019， 2019: 8012979[2022-01-14]. https://doi. org/10.1155/2019/8012979.

ZHENG L H， ZHAO Y H， FENG H L， et al. Endocrine resistance in breast cancer. Climacteric，2014，17(5): 522–528.

YANG G， WANG B， SUN D， et al. Genetic association study between TAB2 polymorphisms and noise-induced-hearing-loss in a Han Chinese population. PLoS One， 2021， 16(5): e0251090[2022-01-14]. https://doi. org/10.1371/journal.pone.0251090.

THIENPONT B， ZHANG L， POSTMA A V， et al. Haploinsufficiency of TAB2 causes congenital heart defects in humans. Am J Hum Genet， 2010，86(6): 839–849.

SHEN C， ZHONG Y， HUANG X， et al. Associations between TAB2 gene polymorphisms and dilated cardiomyopathy in a Chinese population. Biomark Med，2020，14(6): 441–450.

CHEN J， YUAN H， XIE K， et al. A novel TAB2 nonsense mutation (p.S149X) causing autosomal dominant congenital heart defects: A case report of a Chinese family. BMC Cardiovasc Disord，2020，20(1): 27.

MICALE L， MORLINO S， CARBONE A， et al. Loss-of-function variants in exon 4 of TAB2 cause a recognizable multisystem disorder with cardiovascular, facial, cutaneous, and musculoskeletal involvement. Genet Med，2022，24(2): 439–453.

ZHU S， PAN W， SONG X， et al. The microRNA miR-23b suppresses IL-17-associated autoimmune inflammation by targeting TAB2, TAB3 and IKK-α. Nat Med，2012，18(7): 1077–1086.

XIA Z P， SUN L， CHEN X， et al. Direct activation of protein kinases by unanchored polyubiquitin chains. Nature，2009，461(7260): 114–119.


Refbacks

  • There are currently no refbacks.