Dataset Information

Genetic association between PAX2 and mullerian duct anomalies in Han Chinese females.

ABSTRACT:

Purpose

The study aims to investigate the genetic association between paired box gene 2 (PAX2) and mullerian duct anomalies (MDA) in Chinese Han females.

Methods

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to identify the genotypes of three tag single nucleotide polymorphisms (SNPs) in PAX2 in 362 MDA cases and 406 controls.

Results

We found that one tag SNP (rs12266644) of PAX2 was associated with susceptibility to MDA. The genotype distributions of the SNP rs12266644 have a statistically significant difference in the MDA patients and controls with a p value = 0.008. In the dominant model, we also observed that the GT + TT genotype increased the risk for MDA (p = 0.015, OR = 1.637, 95 % CI = 1.096-2.443).

Conclusion

The polymorphism rs12266644 of PAX2 might be a risk factor for MDA in Chinese Han females.

SUBMITTER: Xu Z

PROVIDER: S-EPMC5330971 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Publications

Genetic association between PAX2 and mullerian duct anomalies in Han Chinese females.

Xu Zuying Z Wu Shinan S Xing Qiong Q Wang Xi X Xiang Huifen H Xu Yuping Y Wang Jing J He Xiaojin X Wang Binbin B Cao Yunxia Y

Journal of assisted reproduction and genetics 20161008 1

<h4>Purpose</h4>The study aims to investigate the genetic association between paired box gene 2 (PAX2) and mullerian duct anomalies (MDA) in Chinese Han females.<h4>Methods</h4>Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to identify the genotypes of three tag single nucleotide polymorphisms (SNPs) in PAX2 in 362 MDA cases and 406 controls.<h4>Results</h4>We found that one tag SNP (rs12266644) of PAX2 was associated with susceptibility to M ...[more]

PMID: 27722936

Similar Datasets

Project description:BackgroundMüllerian duct anomalies (MDAs) are congenital developmental disorders that present as a series of abnormalities within the reproductive tracts of females. Genetic factors are linked to MDAs and recent advancements in whole-exome sequencing (WES) provide innovative perspectives in this field. However, relevant mechanism has only been investigated in a restricted manner without clear elucidation of respective observations.MethodsOur previous study reported that 2 of 12 patients with MDAs harbored the CHD1L variant c.348-1G>C. Subsequently, an additional 85 MDAs patients were recruited. Variants in CHD1L were screened through the in-house database of WES performed in the cohort and two cases were identified. One presented with partial septate uterus with left renal agenesis and the other with complete septate uterus, duplicated cervices and longitudinal vaginal septum. The pathogenicity of the discovered variants was further assessed by molecular dynamics simulation and various functional assays.ResultsUltimately, two novel heterozygous CHD1L variants, including a missense variant c.956G>A (p.R319Q) and a nonsense variant c.1831C>T (p.R611*) were observed. The variants were absent in 100 controls. Altogether, the contribution yield of CHD1L to MDAs was calculated as 4.12% (4/97). All three variants were assessed as pathogenic through various functional analysis. The splice-site variant c.348-1G>C resulted in a 11 bp sequence skipping in exon 4 of CHD1L and led to nonsense mediated decay of its transcripts. Unlike WT CHD1L, the truncated R611* protein mislocalized to the cytoplasm, abolish the ability of CHD1L to promote cell migration and failed to interact with PARP1 owing to the loss of macro domain. The R319Q variant exhibited conformational disparities and showed abnormal protein recruitment behavior through laser microirradiation comparing with the WT CHD1L. All these variants impaired the CHD1L function in DNA damage repair, thus participating in MDAs.ConclusionsThe current study not only expands the mutational spectrum of CHD1L in MDAs but determines three variants as pathogenic according to ACMG guidelines with reliable functional evidence. Additionally, the impairment in DNA damage repair is an underlying mechanism involved in MDAs.

Dataset Information

Genetic association between PAX2 and mullerian duct anomalies in Han Chinese females.

Purpose

Methods

Results

Conclusion

Publications

Genetic association between PAX2 and mullerian duct anomalies in Han Chinese females.

Similar Datasets

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