Mutation analysis of the WNT4 gene in Han Chinese women with premature ovarian failure

BACKGROUND: The WNT4 gene plays an important role in female sex determination and differentiation. It also contributes to maintaining of the ovaries and the survival of follicles. METHODS: We sequenced the coding region and splice sites of WNT4 in 145 Han Chinese women with premature ovarian failure (POF) and 200 healthy controls. RESULTS: Only one novel variation, in Exon 2 (195C > T), was detected among the women with POF. However, this synonymous variation did not result in a change in amino acid sequence (65 Asp > Asp). No further variants were found in any of the samples. CONCLUSION: Although we cannot provide any evidence that it is a possible disease-causing gene, this study is the first attempt to investigate the possible role of WNT4 in Han Chinese women with POF

Polymorphisms in the Presumptive Promoter Region of the SLC2A9 Gene Are Associated with Gout in a Chinese Male Population

BACKGROUND: Glucose transporter 9 (GLUT9) is a high-capacity/low-affinity urate transporter. To date, several recent genome-wide association studies (GWAS) and follow-up studies have identified genetic variants of SLC2A9 associated with urate concentrations and susceptibility to gout. We therefore investigated associations between gout and polymorphisms and haplotypes in the presumptive promoter region of GLUT9 in Chinese males. METHODOLOGY/PRINCIPAL FINDINGS: The approximately 2000 bp presumptive promoter region upstream of the start site of exon 1 of GLUT9 was sequenced and subjected to genetic analysis. A genotype-phenotype correlation was performed and polymorphisms-induced changes in transcription factor binding sites were predicted. Of 21 SNPs identified in GLUT9, five had not been previously reported. Two of the SNPs (rs13124007 and rs6850166) were associated with susceptibility to gout (p = 0.009 and p = 0.042, respectively). The C allele of rs13124007 appeared to be the risk allele for predisposition to gout (p = 0.006, OR 1.709 [95% CI 1.162-2.514]). For rs6850166, an increased risk of gout was associated with the A allele (p = 0.029, OR 1.645 [95% CI 1.050-2.577]). After Bonferroni correction, there was statistically difference in rs13124007 allele frequencies between gout cases and controls (P = 0.042). Haplotype analyses showed that haplotype GG was a protective haplotype (p = 0.0053) and haplotype CA was associated with increased risk of gout (p = 0.0326). Genotype-phenotype analysis among gout patients revealed an association of rs13124007 with serum triglycerides levels (P = 0.001). The C to G substitution in polymorphism rs13124007 resulted in a loss of a binding site for transcription factor interferon regulatory factor 1 (IRF-1). CONCLUSIONS/SIGNIFICANCE: Polymorphisms rs13124007 and rs6850166 are associated with susceptibility to gout in Chinese males

Mutation analysis of the WNT4 gene in Han Chinese women with premature ovarian failure

Abstract Background The WNT4 gene plays an important role in female sex determination and differentiation. It also contributes to maintaining of the ovaries and the survival of follicles. Methods We sequenced the coding region and splice sites of WNT4 in 145 Han Chinese women with premature ovarian failure (POF) and 200 healthy controls. Results Only one novel variation, in Exon 2 (195C > T), was detected among the women with POF. However, this synonymous variation did not result in a change in amino acid sequence (65 Asp > Asp). No further variants were found in any of the samples. Conclusion Although we cannot provide any evidence that it is a possible disease-causing gene, this study is the first attempt to investigate the possible role of WNT4 in Han Chinese women with POF.</p

Association analysis between <it>HOXD9</it> genes and the development of developmental dysplasia of the hip in Chinese female Han population

Abstract Background Developmental dysplasia of the hip (DDH) is a congenital or acquired deformation or misalignment of the hip joint which affects mainly females. We hypothesized that HOXD9 gene could be regulated in acetabular size or shape and related in DDH developing. Methods Two hundred and nine Chinese Han female DDH patients and 173 ethnic, age matched healthy female controls were genotyped for HOXD9 two tag SNPs using sequenom method. Results One of the two tag SNPs, rs711822, was not shown significantly differences in genotypic or allelic distribution between case and control group. Comparing the genotypic distribution of rs711819, there was significant differences between DDH patients group and control group (χ2 = 7.54, df =2, P =0.023), and the association to DDH developing reached significance (P =0.045, OR =1.79, 95 % CI: 1.01-3.17 by dominant mode). Conclusion In conclusion, the association between one tag SNP of HOXD9 gene and the development of DDH reach significant in our study population, this result indicate the positive correlation between HOXD9 gene and DDH developing. Further study in larger sample size and different population as well as functional studies will help to understand the pathogenesis of DDH.</p

Demographic and clinical characteristics (Mean±SD) of the study population.

<p>Demographic and clinical characteristics (Mean±SD) of the study population.</p

The haplotype association among all 21 SNPs in the GLUT9 gene.

<p>The haplotype association among all 21 SNPs in the GLUT9 gene.</p

The associations in the distributions of genotypes and allele frequency for two polymorphisms (rs13124007 and rs6850166) in the GLUT9 gene in cases and controls.

<p>The associations in the distributions of genotypes and allele frequency for two polymorphisms (rs13124007 and rs6850166) in the GLUT9 gene in cases and controls.</p

Association between the polymorphisms (rs13124007 and rs6850166) and characteristics among gout patients.

<p>*The major allele was referred to as allele 1 and the minor allele as allele 2.</p>#<p>Hypertension was defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg or receiving antihypertensivedrug treatment in a patient with a history of hypertension.</p> <p>Diabetes was defined on the basis of fasting blood glucose ≥7.0 mmol/l (126 mg/dl) or non-fasting blood glucose ≥11.1 mmol/l(200 mg/dl) and/or treatment of diabetes.</p>&<p>Obesity is defined as a BMI of 30 and above by World Health Organization (WHO).</p

Genotype distribution and allele frequencies of promoter of the human GLUT9 gene in cases and controls.

*<p>Novel SNP not reported in public database before.</p>#<p>The major allele was referred to as allele 1 and the minor allele as allele 2.</p