SIRT1 Gene Single Nucleotide Polymorphisms and Female Infertility: A
Cross Sectional Study In Pakistan
Aim & Objective: Silent information Regulators (SIRT1) gene stimulates
the expression of antioxidants and repairs damaged cells. It affects the
mitochondrial activity within the oocytes to overcome the oxidant
stress. We aimed to assess an association of SIRT1 polymorphism (Tag
SNPs rs10509291 and rs12778366) with fertility, and assess serum levels
of follicle stimulating hormone (FSH), luteinizing hormone (LH),
estradiol, progesterone, manganese superoxide (MnSOD) and SIRT1.
Material and Methods: In this cross-sectional study, 207 fertile and 135
infertile subjects between the ages of 18-45 year were recruited.
Polymerase chain reaction (PCR) was performed; products were
electrophoresed in a 2% agarose gel. Descriptive analysis of continuous
variables was expressed as mean ± standard deviation. Mann-Whitney test
was performed for comparison of groups, p value <0.001 was
considered significant. Single Nucleotide Polymorphism (SNP) data was
analyzed by applying chi-squared statistics. Results: All subjects were
age matched (p = 0.896). SIRT1 levels were significantly lower in
infertile females when compared with fertile subjects
(p<0.001). AA (rs10509291) and CC (rs12778366) variant
frequency was higher in the infertile than fertile subjects
(p<0.01). Similarly, the frequency of A allele (rs10509291)
and C allele (rs12778366) was higher in infertile subjects
(p<0.001). Infertile females (29%) showed existence of SNP
rs10509291 while 49% demonstrated genetic variation of rs12778366.
MnSOD and SIRT1 levels were found to be lower in these subjects.
Conclusion: Presence of SIRT1 genetic variants (rs10509291 and
rs12778366) apparently disturbs the expression of SIRT1 deteriorating
mitochondrial antioxidant function within the oocytes, instigating
oxidative stress within. Their probable effect on modulating oocyte
maturation may be the cause of infertility in females.