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AB200. Association of rs3129878 and rs498422in the HLA region with non-obstructive azoospermia in the Han Chinese population

ABSTRACT: Objective The previous genome-wide association study (GWAS) of non-obstructive azoospermia (NOA) in the Han Chinese populations identified two NOA-risk loci (rs498422 and rs3129878) within the HLA region, and provided strong evidence for the genetic influence of male infertility. A further case-control study found that only rs3129878 remained to be significantly associated with NOA in the Japanese population. Therefore, we conducted the association study to further validate whether the risk of NOA caused by these two SNPs was still existed in an independent Han Chinese male population, consisting of 550 NOA cases and 555 normal controls. Design A case-control study of the NOA susceptibility genes within the HLA region associations. Materials and methods These two SNPs were analyzed in 550 NOA patients and 555 controls of Chinese origin using direct sequencing. Then, the genotype and allele distributions of them were further analyzed using the online software SHEsis (http://analysis.bio-x.cn). Results The association studies strongly supported the significant association ofrs498422 and rs3129878 with NOA for both genotype and allele distributions (P=0.047 and P=1.87×10, respectively). Conclusions In our replication study of Chinese samples, we provided genetic evidence for the contribution of these two NOA-risk SNPs within the HLA genes region in predicting males at high risk of NOA in Han Chinese population. Considering genetic differences among populations, future validating studies in independent samples are suggested.

SUBMITTER: Zou S

PROVIDER: S-EPMC4708476 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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AB186. Association study between polymorphisms of PRMT6, PEX10, SOX5, and non-obstructive azoospermia in the Han Chinese population

Project description:A previous genomewide association study of non-obstructive azoospermia (NOA) in the Han Chinese population identified three risk loci (rs12097821, rs2477686, and rs10842262) and provided strong evidence for a genetic influence in male infertility. However, recently, a follow-up study of these single nucleotide polymorphism (SNP) loci in the Japanese population showed that none of them were significantly associated with NOA. Therefore, we conducted an association study, consisting of 550 NOA cases and 555 normal controls, to further validate whether the risk of those three SNPs still existed in an independent Han Chinese male population. The association studies did not support the association of rs12097821 and rs2477686 with NOA for both genotype and allele distributions, but rs10842262 in the SOX5 gene was significantly associated with NOA (chi square =9.31; P=0.0095 and chi square =9.27; P=0.0023, respectively). Our study provides genetic evidence for SOX5 polymorphism in NOA, contributing to predicting males at high risk of NOA in Han Chinese population. Considering genetic differences among populations, future validating studies in independent samples are suggested

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Association Between Polymorphisms in the Angiotensin-Converting Enzyme Gene and Non-Obstructive Azoospermia in the Chinese Han Population from Northeast China.

Project description:BACKGROUND Genetic defects are commonly observed in infertile males, although the majority of cases remain idiopathic. In recent years, the relationship between single-nucleotide polymorphisms (SNPs) and male infertility has received increasing attention. The objective of this study was to explore the relationship between non-obstructive azoospermia (NOA) and single-nucleotide polymorphisms in the angiotensin-converting enzyme gene (ACE) using ligase detection reaction (LDR)-PCR. MATERIAL AND METHODS A retrospective study was performed and we screened 4 ACE SNPs (rs4316, rs4331, rs4343, and rs4362) in 121 NOA cases and 256 control subjects by LDR-PCR. The relationship between SNPs and NOA was analyzed. RESULTS ACE SNPs were in Hardy-Weinberg equilibrium (P=0.089 for rs4331, P=0.089 for rs4343, P=0.089 for rs4316, and P=0.381 for rs4362). The allelic and genotypic frequencies of the 4 SNPs were not significantly different between cases and controls (P=0.123 for rs4331, P=0.123 for rs4343, P=0.123 for rs4316, and P=0.179 for rs4362). Haplotype analysis showed the existence of 3 haplotypes, TGAC, CAGT, and TGAT, which showed statistical significance of 0.889, 0.889, and 0.781, respectively, between cases and controls. CONCLUSIONS No significant association was found between ACE SNPs rs4316, rs4331, rs4343, or rs4362 and NOA in the Chinese Han population of Northeast China.

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Novel Hemizygous Mutations of <i>TEX11</i> Cause Meiotic Arrest and Non-obstructive Azoospermia in Chinese Han Population.

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X chromosome-wide identification of SNVs in microRNA genes and non-obstructive azoospermia risk in Han Chinese population.

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Association of ESX1 gene variants with non-obstructive azoospermia in Chinese males.

Project description:Genetic factors are one of the most important causes of non-obstructive azoospermia (NOA). ESX1 is an X-linked testis-biased expressed gene, and a potential biomarker for testicular sperm retrieval in NOA patients, yet few systematic studies have investigated its association with NOA. Here, we performed selected exonic sequencing in a large cohort of Chinese males, and four novel missense mutations (including one compound mutation), one novel synonymous mutation of ESX1 unique to NOA patients were identified. We analyzed the effects of ESX1 mutations on cyclin A degradation and cell cycle progression by immunoprecipitation assay and flow cytometry, and found that the compound mutant p.[P365R; L366V] ESX1 compromised the stabilizing effect of ESX1 on polyubiquitinated cyclin A, thereby causing the failure of M phase arrest in cells. Further studies showed that the deleterious effect of the compound mutations on ESX1 protein function was attributed to p.P365R but not p.L366V alteration. The novel ESX1 mutation p.P365R might confer high risk for NOA in Han Chinese population, probably via affecting cell cycle control.

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Association of single nucleotide polymorphisms in the USF1, GTF2A1L and OR2W3 genes with non-obstructive azoospermia in the Chinese population.

Project description:To research the association between the single nucleotide polymorphisms (SNPs) of three spermatogenesis-related genes (USF1, GTF2A1L and OR2W3) and non-obstruction azoospermia (NOA).We investigated 361 NOA cases and 368 controls from the Chinese Han population, and we used Sequenom iplex technology to analyze the candidate 9 SNPs from the USF1, GTF2A1L and OR2W3 genes.In this study, we found that the variant rs2516838 of USF1 was associated with NOA susceptibility (P?=?0.020, OR?=?1.436), and the haplotype TCG of the variants rs1556259, rs2516838, and rs2774276 of USF1 conferred an increased risk of NOA (P?=?0.019, OR?=?1.436). Furthermore, we found that the rs11204546 genotype of OR2W3 and the rs11677854 genotype of GTF2A1L were correlated with the FSH level in the patients (P?=?0.004 and P?=?0.018, respectively).Our results provided a new insight into susceptibility of USF1 variant with male infertility. Clinically, the SNPs (rs11204546 of OR2W3 and rs11677854 of GTF2A1L ) might be additional valuable molecular predictive markers for assessing the treatment of NOA patients.

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Genetic study of Hormad1 and Hormad2 with non-obstructive azoospermia patients in the male Chinese population.

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2018-09-30 | GSE119367 | GEO

The association of <i>HLA/KIR</i> genes with non-small cell lung cancer (adenocarcinoma) in a Han Chinese population.

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