<abstract xmlns="http://www.w3.org/1999/xhtml">The objective of this study was to compare the CYP 21A2 genetic profiles of couples with unexplained fertility problems (UFP) with genetic profiles of healthy controls (HCs). Furthermore, we analyzed associations between mutations in the <italic>CYP21A2</italic> gene and various clinical and laboratory parameters. Allele-specific polymerase chain reaction (PCR) was used in 638 probands with UFP and 200 HCs. Statistic analysis with χ2 was used to study the association of mutations with infertility. The effect of mutations on particular clinical and laboratory parameters was assessed with the analysis of variance (ANOVA) test. With regard to the <italic>CYP21A2</italic> gene, 0.6% of probands with UFP and 0.5% of HCs were positive for the c.290-13A/C>G mutation; 0.6% of probands with UFP and 1.5% of HCs were positive for the p.I172N mutation; there were no probands with UFP positive for the p.P30L mutation, whereas 0.5% of HCs were; and 0.2% of probands with UFP and 0.5% of HCs were found to have the p.V281L mutation. We found a significant association between c.290-13A/C>G mutation and the frequency of significant hormone deviations (χ2 = 6.997, <italic>p</italic> = 0.008). Similar association was also observed between the c.29013A/C>G mutation and the frequency of polycystic ovary syndrome (PCOS) (χ2 = 16.775, <italic>p</italic> = 0.000). Our findings indicate that no significant difference in the prevalence of CYP 21A2 mutations can be found in probands with UFP when compared with HCs without infertility history. The results also imply the significant association of the c.290-13A/ C>G mutation in the <italic>CYP21A2</italic> gene, not only with the frequency of PCOS, but also with the frequency of significant hormone deviations.</abstract>

The objective of this study was to compare the CYP 21A2 genetic profiles of couples with unexplained fertility problems (UFP) with genetic profiles of healthy controls (HCs). Furthermore, we analyzed associations between mutations in the CYP21A2 gene and various clinical and laboratory parameters. Allele-specific polymerase chain reaction (PCR) was used in 638 probands with UFP and 200 HCs. Statistic analysis with χ2 was used to study the association of mutations with infertility. The effect of mutations on particular clinical and laboratory parameters was assessed with the analysis of variance (ANOVA) test. With regard to the CYP21A2 gene, 0.6% of probands with UFP and 0.5% of HCs were positive for the c.290-13A/C>G mutation; 0.6% of probands with UFP and 1.5% of HCs were positive for the p.I172N mutation; there were no probands with UFP positive for the p.P30L mutation, whereas 0.5% of HCs were; and 0.2% of probands with UFP and 0.5% of HCs were found to have the p.V281L mutation. We found a significant association between c.290-13A/C>G mutation and the frequency of significant hormone deviations (χ2 = 6.997, p = 0.008). Similar association was also observed between the c.29013A/C>G mutation and the frequency of polycystic ovary syndrome (PCOS) (χ2 = 16.775, p = 0.000). Our findings indicate that no significant difference in the prevalence of CYP 21A2 mutations can be found in probands with UFP when compared with HCs without infertility history. The results also imply the significant association of the c.290-13A/ C>G mutation in the CYP21A2 gene, not only with the frequency of PCOS, but also with the frequency of significant hormone deviations.

Detection of mutations in the <italic>CYP21A2</italic> gene: genotype-phenotype correlation in Slovenian couples with conceiving problems

Laboratory of Medical Genetics, University Clinical Centre Maribor, Maribor,

Medical Faculty, University of Maribor, Maribor,

Balkan Journal of Medical Genetics

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Detection of mutations in the  gene: genotype-phenotype correlation in Slovenian couples with conceiving problems

The objective of this study was to compare the CYP 21A2 genetic profiles of couples with unexplained fertility problems (UFP) with genetic profiles of healthy...

Parameters/Clinical Indicator	n	%
A thyroid disease	19	6.1
Hor	40	12.5
Est	22	6.9
Prog	3	0.9
An autoimmune disease	6	1.9
PCOS	18	5.6
BMI	44	13.8

	Males		Females		χ²	p Value
Mutations	n	%	n	%
c.290-13A/C>G	2	0.6	2	0.6	0.043	0.979
p.I172N	2	0.6	2	0.6	1.389	0.499
p.P30L	0	0.0	0	0.0	0.000	0.000
p.V281L	1	0.3	0	0.0	1.405	0.495
Total	5	1.6	4	1.3	2.254	0.324

Mutations	Probands (n=638) (%)	Controls (n=200) (%)	χ²	p Value
c.290-13A/C>G	4 (0.6)	1 (0.5)	0.043	0.836
p.I172N	4 (0.6)	3 (1.5)	1.389	0.239
p.P30L	0 (0.0)	1 (0.5)	3.183	0.074
p.V281L	1 (0.2)	1 (0.5)	0.749	0.387
Total	9 (1.4)	6 (3.0)	2.167	0.141

	Total	Males	Females
n (probands)	638	319	319
Mean age	32.9	33.8	32.0
Age range (years)	21-44	23-44	21-44

Clinical Parameters	c.290-13A/C>G (χ²;pvalue)	p.I172N (χ²;pvalue)	p.P30L (χ²;pvalue)	p.V281L (χ²;pvalue)
A thyroid disease	0.257; 0.613	0.257; 0.613	‒;	0.064; 0.801
Hor	0.581; 0.446	0.581; 0.446	‒;	6.997; 0.008
Est	0.300; 0.584	0.300; 0.584	‒;	0.074; 0.785
Prog	0.038; 0.845	0.038; 0.845	‒;	0.010; 0.922
An autoimmune disease	0.078; 0.781	0.078; 0.781	‒;	0.019; 0.890
PCOS	0.242; 0.623	0.242; 0.623	‒;	16.775; 0.000
BMI	0.648; 0.421	0.648; 0.421	‒;	0.161; 0.689

Detection of mutations in the CYP21A2 gene: genotype-phenotype correlation in Slovenian couples with conceiving problems

Article Category: Original Article

Published Online: Jul 09, 2016

Page range: 25 - 32

DOI: https://doi.org/10.1515/bjmg-2015-0082

Keywords
gene, genetics, infertility, mutations, unexplained infertility problems (UFP), healthy controls (HCs)

© 2016 Walter de Gruyter GmbH, Berlin/Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Number and percentage of female probands with the deviation of laboratory parameters from the reference value and the presence of the clinical indicators.

Number and percentage of mutations discovered in the male and females probands.

The c.290-13A/C>G, p.I172N, p.P30L and p.V281L mutation frequencies in couples with unexplained fertility problems and controls.

Ages, mean ages and age ranges of the male and female probands.

Comparison of clinical parameters of the entire group of female probands with the c.290-13A/C>G, p.I172N, p.P30L and p.V281L mutations and female probands without the c.290-13A/C>G, p.I172N, p.P30L and p.V281L mutations.

Detection of mutations in the CYP21A2 gene: genotype-phenotype correlation in Slovenian couples with conceiving problems

Article Category: Original Article

Published Online: Jul 09, 2016

Page range: 25 - 32

DOI: https://doi.org/10.1515/bjmg-2015-0082

Keywordsgene, genetics, infertility, mutations, unexplained infertility problems (UFP), healthy controls (HCs)

© 2016 Walter de Gruyter GmbH, Berlin/Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Number and percentage of female probands with the deviation of laboratory parameters from the reference value and the presence of the clinical indicators.

Number and percentage of mutations discovered in the male and females probands.

The c.290-13A/C>G, p.I172N, p.P30L and p.V281L mutation frequencies in couples with unexplained fertility problems and controls.

Ages, mean ages and age ranges of the male and female probands.

Comparison of clinical parameters of the entire group of female probands with the c.290-13A/C>G, p.I172N, p.P30L and p.V281L mutations and female probands without the c.290-13A/C>G, p.I172N, p.P30L and p.V281L mutations.

Keywords
gene, genetics, infertility, mutations, unexplained infertility problems (UFP), healthy controls (HCs)