MTHFR-c 677C>T polymorphism and male infertility: An analysis in a cohort of Pakistani men / Polimorfismo MTHFR-c 677C>T e infertilidad masculina: un análisis en una cohorte de hombres pakistaníes

Objective: To analyze existence of an association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with male infertility. Materials and methods: A case–control study was conducted from June 2017 to August 2018 in which 88 infertile and 40 fertile were recruited. Polymerase chain reaction (PCR) – restriction fragment length polymorphism (RFLP) assay was carried out to study the allelic frequency of C677T polymorphism. The differences in allelic and genotypic frequencies of C677T locus between fertile and infertile groups were evaluated by the Pearson chisquare test. A logistic regression model was used to calculate Odds ratios and 95% confidence intervals, p value<0.05 was considered significant. The Hardy–Weinberg equilibrium was tested using HWE software. Results: In infertile subjects, frequency distribution of CC allele was (60.2%), the CT allele was (30.7%) the TT allele was (9.1%) and in the fertile controls the frequency was CC allele (75%), CT allele (20%) and TT allele (5%) respectively. Analysis revealed MTHFR 677 CC genotype associated significantly with male infertility (p<.046, OR=2.385; 95% CI=1.014–5.608); Frequency of CT (30.7%) and TT (9.1) genotypes were higher in infertile men as compared to CT (20%) TT (5%) in fertile controls but statistically these were not significantly different (p=0.097; OR=0.455; CI=0.179–1.153 and p=0.431; OR=0.526; CI=0.107–2.599 respectively). Significant association of age and BMI with MTHFR genotypes and infertility was observed. Conclusion: Our results showed that MTHFR C677T polymorphism is not a risk factor for male infertility in our Pakistani population. (AU)

Objetivo: Observar el efecto del polimorfismo C677T en metilenetetrahidrofolato reductasa (MTHFR) en la infertilidad masculina. Materiales y métodos: Se realizó un estudio de casos y controles desde junio de 2017 hasta agosto de 2018 en el que se reclutaron 88 infértiles y 40 fértiles. Se llevó a cabo el ensayo reacción en cadena de la polimerasa (PCR) - polimorfismo de longitud de fragmento de restricción (RFLP) para estudiar la frecuencia alélica del polimorfismo C677T. La prueba de chi-cuadrado de Pearson se utilizó para estimar las diferencias en las frecuencias alélicas y genotípicas del locus C677T entre fértiles e infértiles. Los cocientes de probabilidad se obtuvieron mediante el análisis de regresión logística con intervalos de confianza del 95%, siendo significativo un valor de p<0,05. Se aplicó el equilibrio Hardy-Weinberg (HWE). Resultados: En sujetos infértiles, la distribución de frecuencia del alelo CC fue del 60,2%, la del alelo CT, del 30,7%, la del alelo TT, del 9,1%, y en los controles fértiles la frecuencia fue alelo CC fue del 75%, la del alelo CT, del 20%, y la del alelo TT, del 5%, respectivamente. El análisis reveló el genotipo CC MTHFR 677 asociado significativamente con infertilidad en los hombres (p<0,046, OR=2,385; IC95%: 1,014-5,608). La frecuencia de los genotipos CT (30,7%) y TT (9,1) fue mayor en hombres infértiles en comparación con CT (20%) y TT (5%) en controles fértiles, pero estadísticamente estos no fueron significativamente diferentes (p=0,097, OR=0,455; IC95%: 0,179-1,153, y p=0,431, OR=0,526; IC95%: 0,107-2,599, respectivamente). Se observó asociación significativa de edad e IMC con genotipos MTHFR e infertilidad. Conclusión: Nuestros resultados mostraron que el polimorfismo MTHFR C677T no está asociado con la infertilidad por factor masculino en nuestra población pakistaní. (AU)

MTHFR-c 677C>T polymorphism and male infertility: An analysis in a cohort of Pakistani men.

OBJECTIVE: To analyze existence of an association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with male infertility. MATERIALS AND METHODS: A case-control study was conducted from June 2017 to August 2018 in which 88 infertile and 40 fertile were recruited. Polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) assay was carried out to study the allelic frequency of C677T polymorphism. The differences in allelic and genotypic frequencies of C677T locus between fertile and infertile groups were evaluated by the Pearson chisquare test. A logistic regression model was used to calculate Odds ratios and 95% confidence intervals, p value<0.05 was considered significant. The Hardy-Weinberg equilibrium was tested using HWE software. RESULTS: In infertile subjects, frequency distribution of CC allele was (60.2%), the CT allele was (30.7%) the TT allele was (9.1%) and in the fertile controls the frequency was CC allele (75%), CT allele (20%) and TT allele (5%) respectively. Analysis revealed MTHFR 677 CC genotype associated significantly with male infertility (p<.046, OR=2.385; 95% CI=1.014-5.608); Frequency of CT (30.7%) and TT (9.1) genotypes were higher in infertile men as compared to CT (20%) TT (5%) in fertile controls but statistically these were not significantly different (p=0.097; OR=0.455; CI=0.179-1.153 and p=0.431; OR=0.526; CI=0.107-2.599 respectively). Significant association of age and BMI with MTHFR genotypes and infertility was observed. CONCLUSION: Our results showed that MTHFR C677T polymorphism is not a risk factor for male infertility in our Pakistani population.

Association of polymorphism c.-124G>A and c.-16 C>T in the promoter region of human INHA gene with altered sperm parameters; A pilot study.

OBJECTIVE: The objective of this was to demonstrate the association of Inhibin α (INHα) c.-124G>A and INHα-c.-16 C>T polymorphisms with altered sperm parameters in a selected male population of Karachi, Pakistan. STUDY DESIGN & SETTINGS: In this pilot study, male subjects were stratified on the basis of the WHO criteria for altered sperm parameters; 83 (cases-altered sperm parameters) and 30 (controls-normal sperm parameters) subjects were included for analysis of INHα-c.124G>A polymorphism and 88 (cases) and 38 (controls) were analysed for INHα -c-16 C>T polymorphism. Genotyping of INHα-c.-124G>A and INHα-c.-16 C>T was performed by PCR-RFLP, genotype distribution in Hardy-Weinberg equilibrium was evaluated by binary logistic regression model. RESULTS: For the c.-124G>A polymorphism in INHα gene, frequency of the three major genotypes in controls was: GG: 80.0%, GA: 20.0% and AA: 0% and in cases was: GG: 59.0%, GA: 30.2% and AA: 10.8%. The GG genotype was significantly associated with male infertility (P < .045, OR = 2.776, 95% CI = 1.025-7.513) while the GA genotype was not significantly associated with infertility (P < .290 OR = 0.580, 95% CI = 0.211-1.593). Frequency of mutant AA genotype was 10.8% in cases (altered sperm parameters) and absent (0%) in normal sperm parameter (controls). The frequencies of three major genotypes CC, CT and TT did not show any significant difference between cases and controls (P > .05). CONCLUSION: The results from our study exhibited a significant association of c.-124G>A polymorphism in the INHα gene promoter region with male infertility in the Pakistani population. A significant association of c.-16 C>T polymorphism with male infertility, however, was not observed. Further large-scale studies should be conducted to confirm this association.