Balkan Journal of Medical Genetics

ASSOCIATION OF THE MTHFR C677T (rs1801133) POLYMORPHISM WITH IDIOPATHIC MALE INFERTILITY IN A LOCAL PAKISTANI POPULATION
Irfan M, Ismail M, Azhar Beg M, Shabbir A, Rashid Kayani A, Kaukab Raja G
*Corresponding Author: Muhammad Irfan, M.Phil., Department of Zoology, Pir Mehr Ali Shah Arid Agriculture University Rawalpindi, Pakistan. Tel: +92-344-551-8382. Email: muhammadirfan11@gmail.com
page: 51

DISCUSSION

Spermatogenesis is a complex process involving about 2000 genes and various non genetic factors. The gene mutations and disrupted expression may distort maturation of spermatocytes. DNA methylation ensures the regulated expression of genes. However, DNA methylation is done only in the presence of methionine. A homocysteine is converted into methionine by MTHFR through transferring a methyl group from methylenetetrahyfrofolate [8]. Therefore, a mutation in the MTHFR such as C677T may reduce methylation of DNA [11]. In addition, a reduced conversion of homocysteine into methionine may lead to hyper-homocysteinemia, and cause DNA and cell membrane damages, testicular arterial sclerosis, and impairment of spermatogenesis [11,15-17]. However, results of most of the molecular epidemiological studies on association of MTHFR 677CT polymorphism and male infertility remain controversial. A total of 20 of 41 studies showed association of the polymorphism with male infertility. Out of four [18-21] studies carried out on African populations, only one ([18] showed a signiﬁcant association of the 677T with infertility in Egyptian men. Furthermore, a study on Moroccan infertile men showed a protective role of the MTHFR 677T polymorphism [22]. Comparatively, more than half the number of Asian studies (14 out of 22) [22-32,36-38,41-42] expressed this association, while only a few Caucasian studies (six out of 15) [44-47,50-51] exhibited it. Similarly, all the studies [22-28] except one [29] reported a signiﬁcant association of the 677T anomaly with male infertility. Seven studies on Indian populations reported contrasting observations to each other [30-36]. Four Indian studies [30-33] showed a signiﬁ-cant association of mutant genotypes with infertility, while three studies [34-36] showed no statistically signiﬁcant difference of 677 C>T variants between infertile and fertile males. Dhillon et al. [35] explained the variations in results that their study included a majority of OAT patients in comparison to the majority of azoospermic cases in the study by Singh et al. [29]. Gupta et al. [30] included both azoospermic and OAT individuals, showing a signiﬁcant association of mutant alleles and genotypes with infertility. It was reported that the three Indian populations studied were not ethnically different [30]. Three [36-38] of ﬁve [36- 40] other Asian studies showed signiﬁcantly higher mutant genotypes in infertile groups than fertile groups of Iranian men. Similarly, studies carried out on Korean infertile men also had contrasting results [41-43]. Moreover, in Caucasian populations, few studies reported that the polymorphism in MTHFR was a risk of male infertility [44-48]. However, other studies inferred that the mutant genotype is not such a risk [49-58]. Moreover, few studies gave contrasting conclusions for the same population [47,48]. Therefore, the differences in the results could be attributed to other factors such as variations in recruitment of subjects, sample size, ethnicity and geographic factors (Tables 3 and 4). The results are also dependent on the reproductive health (testicular, hormonal, and epididymal, etc.), general health (infections, surgeries, fever and antibodies, etc.) and lifestyle factors (clothing, occupation, smoking, caffeine intake, etc.), which were not addressed while selecting subjects in many of the previous studies. There were eight studies [18,22,23,26,27,31,37,49] that showed association of 677T with male infertility and seven studies [20,39,40,50-52,58] that lack association and did not mention criteria of selection of infertile men. Furthermore, nine studies [23,24,26-28,32,37,38,47] showing association and eight studies [19,28,34,39,40,48,50,57] that showed no association, did not mention selection criteria of fertile men as a control group (data not shown). In addition, the MTHFR C677T association with male infertility was also affected by folate supplementation, usually prescribed in infertility. The status of folate and supplementation is not mentioned in the previous studies except four [34,36,42,55]. Although a single study that took folate levels as a factor of infertility in Caucasian men also found no association of 677T with male infertility, we can assume, depending on the socioeconomic and health facilities that the Caucasians may have comparatively more chances of folate supplementation than Asians, thus lowering the association of 677T with infertility [42,59,60]. The previous studies described that 35.0% of the Pakistani population is folate deﬁcient (61) and no organized folate supplementation program is currently working for the general population.

Number 27 VOL. 27 (2), 2024	Number 27 VOL. 27 (1), 2024
Number 26 Number 26 VOL. 26(2), 2023 All in one	Number 26 VOL. 26(2), 2023
Number 26 VOL. 26, 2023 Supplement	Number 26 VOL. 26(1), 2023
Number 25 VOL. 25(2), 2022	Number 25 VOL. 25 (1), 2022
Number 24 VOL. 24(2), 2021	Number 24 VOL. 24(1), 2021
Number 23 VOL. 23(2), 2020	Number 22 VOL. 22(2), 2019
Number 22 VOL. 22(1), 2019	Number 22 VOL. 22, 2019 Supplement
Number 21 VOL. 21(2), 2018	Number 21 VOL. 21 (1), 2018
Number 21 VOL. 21, 2018 Supplement	Number 20 VOL. 20 (2), 2017
Number 20 VOL. 20 (1), 2017	Number 19 VOL. 19 (2), 2016
Number 19 VOL. 19 (1), 2016	Number 18 VOL. 18 (2), 2015
Number 18 VOL. 18 (1), 2015	Number 17 VOL. 17 (2), 2014
Number 17 VOL. 17 (1), 2014	Number 16 VOL. 16 (2), 2013
Number 16 VOL. 16 (1), 2013	Number 15 VOL. 15 (2), 2012
Number 15 VOL. 15, 2012 Supplement	Number 15 Vol. 15 (1), 2012
Number 14 14 - Vol. 14 (2), 2011	Number 14 The 9th Balkan Congress of Medical Genetics
Number 14 14 - Vol. 14 (1), 2011	Number 13 Vol. 13 (2), 2010
Number 13 Vol.13 (1), 2010	Number 12 Vol.12 (2), 2009
Number 12 Vol.12 (1), 2009	Number 11 Vol.11 (2),2008
Number 11 Vol.11 (1),2008	Number 10 Vol.10 (2), 2007
Number 10 10 (1),2007	Number 9 1&2, 2006
Number 9 3&4, 2006	Number 8 1&2, 2005
Number 8 3&4, 2004	Number 7 1&2, 2004
Number 6 3&4, 2003	Number 6 1&2, 2003
Number 5 3&4, 2002	Number 5 1&2, 2002
Number 4 Vol.3 (4), 2000	Number 4 Vol.2 (4), 1999
Number 4 Vol.1 (4), 1998	Number 4 3&4, 2001
Number 4 1&2, 2001	Number 3 Vol.3 (3), 2000
Number 3 Vol.2 (3), 1999	Number 3 Vol.1 (3), 1998
Number 2 Vol.3(2), 2000	Number 2 Vol.1 (2), 1998
Number 2 Vol.2 (2), 1999	Number 1 Vol.3 (1), 2000
Number 1 Vol.2 (1), 1999	Number 1 Vol.1 (1), 1998

About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact