Association of TCF7L2 Gene Variant (rs12255372) with Polycystic Ovary Syndrome and its Effect Modification of the Disease Phenotype.

Polycystic ovary syndrome (PCOS) and type-2 diabetes mellitus (T2DM) share common genetic features. Transcription factor 7-like-2 (TCF7L2) is consistently studied T2DM susceptibility locus. However, limited studies on TCF7L2 have failed to demonstrate any link with the PCOS risk. Therefore, we investigated the association of TCF7L2 polymorphic variant (rs12255372) with the PCOS risk. We recruited 120 PCOS cases, diagnosed as per Rotterdam 2003 criteria, and an equal number of age-matched controls. Besides a detailed clinical assessment, subjects underwent biochemical and hormonal profiling. Genotyping for rs12255372 was done by PCR-RFLP. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs) of genotype-phenotype correlations. The PCOS cases reported fewer menstrual cycles per year and exhibited signs of hyperandrogenism. The heterozygous genotype of rs12255372 was strongly associated with the PCOS risk (OR = 2.00; 95%CI: 1.07-3.76). Unlike controls, only 3 cases harbored TT genotype, and the PCOS risk persisted in the dominant model (GT + TT) as well. Moreover, we found a synergistic effect modification by the variant genotype in the subjects who had family histories of T2DM, hirsutism, or menstrual irregularities. We report a significant association of the TCF7L2 polymorphic variant rs12255372 with the PCOS risk.

Nanobioremediation: A sustainable approach towards the degradation of sodium dodecyl sulfate in the environment and simulated conditions.

Nanotechnology has gained huge importance in the field of environmental clean-up today. Due to their remarkable and unique properties, it has shown potential application for the remediation of several pesticides and textile dyes. Recently it has shown positive results for the remediation of sodium dodecyl sulfate (SDS). One of the highly exploited surfactants in detergent preparation is anionic surfactants. The SDS selected for the present study is an example of anionic linear alkyl sulfate. It is utilized extensively in industrial washing, which results in the high effluent level of this contaminant and ubiquitously toxic to the environment. The present review is based on the research depicting the adverse effects of SDS in general and possible strategies to minimizing its effects by bacterial degradation which are capable of exploiting the SDS as an only source of carbon. Moreover, it has also highlighted that how nanotechnology can play a role in the remediation of such recalcitrant pesticides.

Implications of risk conferred by 5p15.33 loci genetic variants; human telomerase reverse transcriptase rs2736098 and rs2736100 in predisposition of bladder cancer.

Background: The polymorphic variations of human telomerase reverse transcriptase (hTERT) gene play an important role in predisposition to carcinogenesis. The current study aimed to elucidate the genetic predisposition to bladder cancer in two important variants, rs2736098 and rs2736100 of hTERT gene. Materials and methods: Confirmed 130 patients of bladder cancer and 200 healthy controls were genotyped by PCR-RFLP to determine different variants of hTERT rs2736098 and rs2736100. Results: hTERT rs2736098 homozygous variant AA genotype frequency was observed to significantly differ 2-fold between cases and controls (26.15% vs. 13.5%) (p = 0.02). In addition, rare 'A' allele significantly differed among two groups (cases: 47% versus controls: 39%: p = 0.03). hTERT rs2736098 was observed to be presented significantly more in high stage tumors (p = 0.02). hTERT rs2736100 genotype AA or variant allele A showed no significant difference between cases and controls. Haplotype CA displayed significantly different pattern of frequency as 0.5 in cases as compared to 0.16 in controls (p < 0.0001). Combination of variant A/G haplotype frequency implicated more in cases than in controls (0.34 vs. 0.14, p = 0.001). Conclusions: It is concluded that hTERT rs2736098 polymorphic variant has a vital role to confer a strong risk to bladder cancer in our population. Further, hTERT haplotypes CA and AG inhTERT could prove to be a promising tool to screen the risk for bladder cancer.

Effect of steroid hormone receptor gene variants PROGINS (Alu insertion) and PGR C/T (rs1042839) as a risk factor for recurrent pregnancy loss in Kashmiri population (North India).

AIM: To unveil and evaluate the association and analyze the incidence and pattern of PGR gene polymorphisms (PROGINS insertion and PGR exon 5-C/T polymorphism) in recurrent pregnancy loss (RPL) couples of Kashmir. METHODS: In this study, analyses of PGR gene polymorphisms in RPL couples were genotyped by amplification-refractory mutation system polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism. RESULTS: Molecular analysis of PGR gene polymorphisms indicated that the genotypic and allelic frequencies of PROGINS insertion and PGR exon 5 C/T polymorphisms of female group in cases and controls to be significantly different and poses risk in predisposition to RPL. Moreover, haplotype analysis in female group revealed that P1P2/CC and P1P2/CT genotype are significantly associated with RPL. CONCLUSION: Our data indicate that the PROGINS insertion and exon 5-C/T polymorphism can act as useful genetic markers in the female group, but needs to be replicated in further studies including various other single nucleotide polymorphisms of PGR gene relevant to pregnancy loss which may contribute to novel therapeutic targets with improved conclusions.

Family history of menstrual irregularity or diabetes mellitus enhances the susceptibility to polycystic ovary syndrome among subjects harboring rs7903146 genetic variant of TCF7L2.

Purpose: TCF7L2 mediated Wnt signaling cascade regulates glucose homeostasis by orchestrating expression, processing, and hepatic clearance of insulin. Type 2 diabetes mellitus (T2DM) and polycystic ovary syndrome (PCOS) significantly overlap in pathophysiological features with insulin resistance as a central driver. While TCF7L2 is the most potent T2DM locus, studies on the association of TCF7L2 with PCOS are limited and inconclusive. Therefore, in addition to expression profiling, the association of TCF7L2 polymorphic variant rs7903146 with PCOS was evaluated. Methods: Using Rotterdam-2003 criteria for the diagnosis, 120 PCOS cases, and 120 age-matched controls were recruited. Subjects underwent clinical, biochemical, and hormonal assessment, followed by genotyping for rs7903146, carried out by PCR-RFLP and TCFL2 expression profiling by qRT-PCR. Genotype-phenotype correlation analysis was performed to evaluate any such associations. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were computed by conditional logistic regression. Results: Higher odds of developing PCOS were observed in the women having a family history (FH) of either T2DM (OR = 3.86, 95% CI:1.90 - 7.83), hirsutism (OR = 4.74. 95%CI: 1.91 - 17.21) or menstrual irregularities (MI) (OR = 3.07, 95%CI: 1.61 - 8.54). The genotypes of rs7903146 did not confer any risk for developing PCOS (OR = 0.46;95%CI: 0.15 - 2.03). However, the elevated risk was seen in the subjects who harbored the variant allele and had FH of either T2DM (OR = 6.71; 95%CI: 1.89 - 23.78) or MI (OR = 9.71; 95% CI:1.89 - 23.78). Conclusion: TCF7L2 polymorphic variant rs7903146 is not independently linked to PCOS risk, but modulates the risk in the subjects having a family history of either T2DM or MI. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01050-y.

Analysis of MNS16A VNTR polymorphic sequence variations of the TERT gene and associated risk for development of bladder cancer.

BACKGROUND: The MNS16A variable number tandem repeat (VNTR) polymorphism of the human telomerase reverse transcriptase (hTERT) gene acts as a regulator of hTERT promoter activity and has been shown to have a role in the predisposition toward various cancers. The current study aimed to investigate the association between MNS16A VNTR alleles and genetic predisposition to bladder cancer in the Kashmir region of northern India. MATERIALS AND METHODS: A total of 130 patients with bladder cancer and 170 age- and gender-matched healthy controls were included in this study. Primer-specific polymerase chain reaction was used to genotype the different variants of VNTR alleles of the MNS16A VNTR polymorphism. RESULTS: Short allele VNTR-243 (SS) genotype frequency significantly differed between cases (9.23%) and controls (3.52%) (OR = 3.08 [95% CI = 1.10-8.61], p = 0.042). The VNTR-243 short allele (S) was found significantly more frequent in bladder cancer cases (28.46%) than controls (20.88%) (OR = 1.50 [95% CI = 1.03-2.19], p = 0.034). Likewise, the long allele (LL) hTERT MNS16A genotype was distributed more frequently in low stage disease versus high stage disease (60.29% vs. 39.70%) (OR = 0.79 [95% CI = 0.39-1.60], p = 0.595). CONCLUSION: The MNS16A VNTR short allele (S) was associated with a higher risk for bladder cancer in our population as compared to long alleles.