Androgen Receptor CAG Repeat Polymorphism and Epigenetic Influence among the South Indian Women with Polycystic Ovary Syndrome

The present study was carried out to assess the role of androgen receptor CAG repeat polymorphism and X chromosome inactivation (XCI) pattern among Indian PCOS women and controls which has not been hitherto explored and also to test the hypothesis that shorter CAG alleles would be preferentially activated in PCOS. CAG repeat polymorphism and X chromosome methylation patterns were compared between PCOS and non-PCOS women. 250 PCOS women and 299 controls were included for this study. Androgen receptor CAG repeat sizes, XCI percentages, and clinical and biochemical parameters were measured. The mean CAG repeat number is similar between the cases (18.74±0.13) and controls (18.73±0.12). The obese PCOS women were significantly more frequent in the <18 and >20 CAG repeat category than the lean PCOS women, yielding a highly significant odds (p = 0.001). Among the women with non-random X-inactivation, alleles with <19 repeats were more frequently activated among cases than controls (p = 0.33). CAG repeat polymorphism by itself cannot be considered as a useful marker for discriminating PCOS. We observed a trend of preferential activation of the shorter allele among the PCOS cases with non random XCI pattern. In the obese PCOS women, this microsatellite variation may account for the hyperandrogenicity to a larger extent than the lean PCOS women

Live recombinant Lactococcus lactis vaccine expressing aerolysin genes D1 and D4 for protection against Aeromonas hydrophila in tilapia (Oreochromis niloticus)

Aims:  To evaluate a live recombinant Lactococcus lactis vaccine expressing aerolysin genes D1 (Lac-D1ae) and/or D4 (Lac-D4ae) in protection against Aeromonas hydrophila in tilapia (Oreochromis niloticus). Methods and Results:  The polymerase chain reaction (PCR)-amplified 250- and 750-bp sequences coding for domains D1 and D4 of aerolysin were individually cloned into pNZ8048 and electrotransformed into L. lactis. The recombinant vaccine candidates were then either orally fed or injected intraperitoneally into tilapia. The development of antibodies in sampled fish compared to control groups implied that the recombinant epitopes expressed in L. lactis were able to elicit an immunogenic response in tilapia. Interestingly, the lower doses of both Lac-D1ae and Lac-D4ae gave higher antibody levels over the study period. Fish immunized with Lac-D1ae and Lac-D4ae together showed the highest level of protection, and the mortality was reduced significantly compared to control strains in both modes of vaccination. Conclusions:  The recombinant L. lactis strain expressing D1 and D4 produced aerolysin-specific serum IgM in tilapia. Both D1 and D4 promoted 55–82% relative per cent survival (RPS) against Aeromonas infection through intraperitoneal injection, whereas the RPS following oral feeding of the vaccine was 70–100%. Significance and Impact of the Study:  The D1 and D4 regions of the aerolysin protein have been successfully identified as immunogenic regions that can elicit antibody production in tilapia and protect against challenge with Aer. hydrophila. A promising oral vaccine using L. lactis harbouring the D1 and D4 regions has been developed to control Aer. hydrophila

Odds ratio for the CAG allele categories (<18 or >20) VS (18–20) in the entire case cohort versus controls taking age and BMI as covariates.

<p>Odds ratio for the CAG allele categories (<18 or >20) VS (18–20) in the entire case cohort versus controls taking age and BMI as covariates.</p

Distribution (%) of PCOS cases and controls according to the qualitative categories of CAG repeats.

<p>χ2 = 2.18, df = 2, p = 0.336; χ2 = 0.212, df = 2, p = 0.899; χ2 = 0.513, df = 2, p = 0.773.</p

Qualitative distribution of CAG biallelic mean among Lean and Obese PCOS cases.

<p>(<b>a</b>) for the three categories,i.e, <18, 18–20 and >20, (<b>b</b>) for extreme CAG categories (<18 and >20) vs the middle range (18–20).</p

Androgenic characteristics among PCOS cases under different biallelic mean categories.

<p>Androgenic characteristics among PCOS cases under different biallelic mean categories.</p

X-inactivation patterns in PCOS cases and controls.

<p>X-inactivation patterns in PCOS cases and controls.</p

Distribution of CAG alleles in PCOS cases and controls.

<p>Distribution of CAG alleles in PCOS cases and controls.</p

Odds ratio for the CAG allele categories (<18 or >20) VS (18–20) in the case cohort (for lean versus obese PCOS cases) taking age as covariate.

<p>Odds ratio for the CAG allele categories (<18 or >20) VS (18–20) in the case cohort (for lean versus obese PCOS cases) taking age as covariate.</p

Distribution of CAG biallelic mean among Lean and Obese PCOS cases.

<p>Distribution of CAG biallelic mean among Lean and Obese PCOS cases.</p