No abstract

Somatic mutations in mitochondrial DNA (mtDNA) have been demonstrated in various tumors. Mitochondrial D-loop is a non-coding region in the mitochondrial genome, which has essential transcription and replication elements, and alterations in this region may affect both these processes. The D-loop has a poly-C tract (PCT) located between 303 and 315 nucleotides known as D310, which has been identified as a frequent hot spot mutation region in human neoplasia. In the present study, 77 pairs of breast tumor and adjacent non-tumorous tissue samples were analyzed by polymerase chain reaction-single-strand conformational polymorphism, restriction fragment length polymorphism, and sequencing to evaluate the frequency of D310 (PCT) mutations and its association with clinicopathologic parameters of breast cancer. Alterations were detected in 25 of 77 (32.5 %) breast cancer samples; these included 7/25 (28 %) cases with heteroplasmy. This is the first study from Asian Indian breast cancer (BC) patients indicating a relatively high frequency of D310 mutations, suggesting that mtDNA instability at D310 may be a common characteristic of BC. However, 66.7 % of the alterations were observed in stage II BC, indicating that this may be a more important change for early progression of the disease rather than its initiation.

Endometriosis and fibroids are estrogen-dependent benign pathologies of the uterus, which account for infertility and pelvic pain along with dysmenorrhea in women. Suppression of the disease and recurrence after discontinuing hormone therapy strongly suggests that these are responsive to hormones, especially estrogen, which acts via its receptor. A T/C SNP in intron 1 and exon 2 boundary of estrogen receptor (ER) α gene recognized by PvuII enzyme has been associated with several female pathologies like breast cancer, osteoporosis, endometriosis and fibroids in various ethnic groups. The aim of the present study was to assess this ER α T/C polymorphism in endometriosis and fibroid patients from Asian Indian population. Genomic DNA was isolated from 367 women, who included 110 cases of endometriosis, 142 cases of uterine fibroids and 115 healthy age matched women volunteers. PCR was carried out to amplify ER α gene followed by restriction digestion with Pvu II. Results indicate a significant association of C allele with both endometriosis [OR = 2.6667, 95% CI = 1.4166 to 5.0199; p < 0.05] and fibroids [2.0833, 95% CI = 1.1327 to 3.8319; p < 0.05]. Further studies are needed in larger population to establish ER α C allele as a risk marker for endometriosis and fibroids in Asian Indian women. Ethnicity, race, diet etc may play a role in susceptibility to endometriosis and fibroids and further studies are warranted in this area.

Diabetes is gradually getting the status of a global epidemic, with India projected as the capital of type 2 diabetes mellitus (T2DM). Nephropathy is an important complication of diabetes and a major cause of end-stage renal disease. Studies from different parts of the world have given controversial results regarding the association of methylene tetrahydrofolate reductase (MTHFR) gene variation with T2DM and diabetic nephropathy (DN). This case-control study assessed the association of MTHFR C677T mutation in T2DM and DN cases. Genotyping of MTHFR was carried out for 236 T2DM cases with diabetes diagnosed for >8 years, having either normoalbuminuria (n=100) or established DN (n=136). One hundred age- and sex-matched healthy individuals with normal blood sugars and no family history of T2DM were selected as controls. This first report from India gives a highly significant odds ratio of 4.0423 (95% confidence interval=1.8753-8.7133), indicating that the MTHFR 677T allele confers a fourfold risk of developing DM in our population. The frequency of the T allele in both the DM and DN groups was similar (i.e., 0.16 and 0.11, respectively), showing no association with the initiation or progression of DN. Individuals with a family history of diabetes or with risk factors such as obesity, hypertension, and impaired glucose tolerance should be screened for MTHFR C677T mutation and may be prescribed folic acid, vitamin B6, and vitamin B12 to assess if this helps in delaying the onset of diabetes.