Abstract
Fumarate hydratase (FH) gene is reported to have specific involvement in syndromic uterine tumors, but its role in nonsyndromic forms is still unclear. Hence, the present study has aimed to screen the role of promoter methylation status and mutations in exon 2 and 7 regions of FH gene in the genesis of nonsyndromic uterine leiomyomas. Leiomyoma and myometrium tissues were collected from 85 hysterectomized uterine specimens. DNA from each of the biopsy was subjected to PCR, methylation-specific restriction assay, and DNA sequencing. In silico analysis was carried out to identify the impact of sequence variants on the protein structure. Chi-square (chi (2)) test was used to compare the promoter methylation proportions of leiomyoma and myometrium tissues. No sequence variants were observed in exon 2 region, but three novel heterozygous germ line sequence variants, i.e., c.1010A > C, c.1021 G > A, and c.1066 T > C in exon 7 region of the FH gene were detected in 14/85 (16.5 %) of the cases examined. In silico analysis results showed that c.1010A > C and c.1021 G > A mutations damage the structure and function of FH, whereas c.1066 T > C mutation is mostly tolerant or neutral. No significant difference of FH promoter methylation status between the leiomyoma (11.76 %) and myometrium (5.88 %) tissues was observed (P = 0.176). Therefore, it is concluded that somatic mutations in FH do not show pronounced effect in nonsyndromic uterine leiomyomas compared to that of their syndromic counterparts. However, higher frequency of FH mutations in leiomyoma cases raises the need to conduct larger number of prospective case-control and family-based studies to assess them as risk markers to nonsyndromic leiomyomas.