Polymorphisms in the TFAM and PGC1-α genes and their association with polycystic ovary syndrome among South Indian women

• Published in: Gene Vol. 641; pp. 129 - 136
• Main Authors: Reddy, Tumu Venkat, Govatati, Suresh, Deenadayal, Mamata, Shivaji, Sisinthy, Bhanoori, Manjula
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.01.2018
• Subjects: Adult; alleles; biogenesis; Case-Control Studies; DNA, Mitochondrial - genetics; DNA-Binding Proteins - genetics; Female; Gene Frequency - genetics; Genetic Association Studies; Genetic Predisposition to Disease - genetics; Genotype; genotyping; Humans; India; luteinizing hormone; mitochondria; Mitochondria - genetics; mitochondrial DNA; Mitochondrial Proteins - genetics; Mitochondrial transcription factor A; mtDNA copy number; pathophysiology; patients; Peroxisome proliferator activated receptor gamma coactivator-1 alpha; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - genetics; peroxisome proliferator-activated receptors; Polycystic ovary syndrome; Polycystic Ovary Syndrome - genetics; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide - genetics; quantitative polymerase chain reaction; restriction fragment length polymorphism; reverse transcriptase polymerase chain reaction; risk; Single nucleotide polymorphism; Transcription Factors - genetics; women; TFs; NRF; D; G; OXPHOS; Mitochondrial transcription factor A; Peroxisome proliferator activated receptor gamma coactivator-1 alpha; SNPs; FSH; GG; SS; Polycystic ovary syndrome; CI; PGC-1α; PCR-RFLP; GS; mtDNA copy number; NRs; PCOS; IIRC; ROS; LD; MCN; TFAM; Single nucleotide polymorphism; LH
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2017.10.010

We investigated the link between polymorphisms in genes involved in mitochondrial biogenesis, mitochondrial transcription factor A (TFAM) and Peroxisome proliferator activated receptor gamma coactivator-1 alpha (PGC-1α) and further studied the role of these genes on the pathophysiology of polycystic ovary syndrome (PCOS). This case-control study was carried out in 118 PCOS cases and 110 controls. In the present study we genotyped three polymorphisms of PGC1-α gene (rs8192678-Gly482Ser, rs13131226 and rs2970856) and polymorphism of TFAM gene (rs1937-+35G/C) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. In addition, to better understand genetic contributions to the pathophysiology of PCOS, mtDNA copy number (MCN) was quantified using a qRT-PCR assay in the subjects. The results revealed that the distribution of genotypes and allele frequency of the PGC-1α Gly482Ser polymorphism in PCOS patients was statistically significant from those of the control group respectively (OR-2.488; 95% CI-1.0673 to 5.7998; P=0.047), (OR-1.6091; 95% CI-1.0955 to 2.3634; P=0.015) indicating that the presence of ‘A’ allele might confer risk to PCOS. Patients with the ‘AA’ genotype showed significantly lower levels of MCN compared with patients with other genotypes. In addition, patients carrying CT genotype of PGC1-α rs2970856 demonstrated significantly higher levels of LH (P=0.030) than TT and CC genotypes. In conclusion, our study indicates that carriers of the PGC-1α rs8192678 ‘Ser’ allele have increased risk of developing PCOS. •The study showed significant differences in the distribution of the genotypes and alleles of the PGC1-α rs8192678 (G/A) SNP.•Patients with AA genotype showed lower levels of MCN compared to patients with GA and GG genotypes of rs8192678 (G/A) SNP.•The ‘Ser’ allele of rs8192678 SNP appears to be a risk factor for the development of PCOS.•Higher levels of LH is observed in patients with the PGC1-α rs2970856 CT genotype when compared to other genotypes.