Evaluating the Impact of rs4025935, rs71748309, rs699947, and rs4646994 Genetic Determinants on Polycystic Ovary Syndrome Predisposition—A Case-Control Study
Abstract
1. Introduction
2. Methodology
2.1. Study Participants and Criteria
2.2. Biochemical Serum Profile: For the First Phase, We Determined Biochemical Serum Profiles of the Patients, Such as HbA1c, Fasting Glucose, Insulin, Serum Lipids, and Hormones
2.3. Extraction and Qualitative Assessment of Genomic DNA
2.4. Genotyping of VEGF rs4646994 I/D, VEGF rs699947 C/A, GSTM1 rs4025935, and GSTT1 rs71748309 Genes
2.5. Preparation of PCR Cocktail
2.6. PCR Program
2.7. PCR Product Visualization in Gels
2.8. VEGF-rs699947 (-2578) C>A Genotyping
Multiplex PCR for GSTT1 and GSTM1 (rs4025935 and rs71748309) Genotyping
3. Results
4. Discussion
Comparative Association of VEGF rs699947 C>A Genotypes in PCOS Patients
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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ARMS-Primers for VEGF-rs699947 C>A | |||||
---|---|---|---|---|---|
Gene | Allele | Sequence | PCR Product | Annealing Temperature | References |
VEGF Fo | 5-CCTTTTCCTCATAAGGGCCTTAG-3 | 353 bp | 58.1 °C | [20,30] | |
VEGF Ro | 5-AGGA AGC AGCT TGGAA AAA TTC-3 | ||||
VEGF FI | A allele | 5-TAGG CCA GAC CCTG GCAA-3 | 149bp | ||
VEGF RI | C allele | 5-GTC TGA TTA TCCA CCC AGAT CG-3 | 243bp | ||
MS-Primers for VEGF rs4646994 I/D | |||||
VEGF F | D-allele | 5′-GCTGAGAGTGGGGCTGACTAGGTA-3′ | 211 bp | 58.8 °C | [31] |
VEGF R | I-allele | 5′-GTTTCTGACCTGGCTATTTCCAGG-3′ | 229 bp | ||
GSTT1 and GSTM1 (rs4025935 and rs71748309) Multiplex PCR Primers for Genotyping | |||||
GSTT1 F | GSTT1 | 5′-TTCCTTACTGGTCCTCACATCTC-3′ | 480 bp | 60 °C | [14] |
GSTT1 R | 5′-TCA CGG GAT CAT GGC CAG CA-3′ | ||||
GSTM1 F | GSTM1 | 5′-GAA CTC CCT GAA AAG CTA AAG C-3′ | 215 bp | ||
GSTM1 R | 5′-GTT GGG CTC AAA TAT ACG GTG G-3′ | ||||
CYP1A1F | CYP1A1 | 5′-GAA CTG CCA CTT CAG CTG TCT-3′ | 312 bp | ||
CYP1A1R | 5′-CA G CTG C AT T T GG AA G T G C TC-3′ |
Characteristic | Controls J | Cases J | p K |
---|---|---|---|
FBG (mmol/L) G | 4.60 ± 0.66 | 7.60 ± 5.16 | <0.0020 |
Age Y | 28.55 ± 4.99 | 29.20 ± 6.10 | 0.420 |
BMI (kg/m2) G | 29.10 ± 4.05 | 27.11 ± 5.90 | <0.004 |
HDL (mmol/L) G | 1.73 ± 0.89 | 1.78 ± 0.91 | <0.0032 |
LDL (mmol/L) G | 2.98 ± 0.70 | 4.98 ± 1.90 | <0.0024 |
Cholesterol (mmol/L) G | 3.80 ± 0.60 | 5.23 ± 0.81 | <0.0023 |
Triglycerides (mmol/L) G | 1.78 ± 0.65 | 3.58 ± 1.41 | <0.0471 |
Luteinizing hormone (mIU/mL) M | 0.09 (0.09–1.90) | 3.65(0.75–9.10) | <0.0040 |
Testosterone (ng/dL) M | 14.90 (6.80–13.55) | 60.15 (46.80–70.30) | <0.0040 |
Estradiol (pmol/L) M | 334.70 ± 249.49 | 386.66 ± 336.79 | 0.169 |
Progesterone (ng/mL) M | 15.55 (3.10–18.10) | 18.30 (2.40–33.10) | <0.0040 |
HOMA-IR G | 4.00 ± 0.82 | 6.00 ± 5.88 | <0.0030 |
Free Insulin (mU/mL) G | 7.90 ± 2.99 | 14.39 ± 5.97 | <0.0021 |
FSH (mIU/mL) M | 0.89 (0.11–5.21) | 4.10 (3.15–6.11) | <0.0040 |
Variables | Controls (125) | PCOS (125) | |||||
---|---|---|---|---|---|---|---|
GSTT1 genotype frequency in case and control groups | |||||||
GSTT1 (+) | 95 (76%) | 54 (43.2%) | |||||
GSTT1 (−) | 30 (24%) | 71 (56.8%) | |||||
Genotype frequencies of GSTM1 in case and control groups | |||||||
GSTM1(+) | 80 (64%) | 50 (40%) | |||||
GSTM1(−) | 45 (36%) | 75 (60%) | |||||
Genotype frequencies of GSTT1/GSTM1 in case and control groups | |||||||
GSTT1 (−) GSTM1 (−) | 42 (33.6%) | 25 (20%) | |||||
GSTT1 (+) GSTM1 (+) | 33 (26.4%) | 31 (24.8%) | |||||
GSTT1 (+) GSTM1 (−) | 30 (24%) | 54 (43.2%) | |||||
GSTT1 (−) GSTM1 (+) | 20 (16%) | 15 (12%) | |||||
Association of GSTM1/GSTT1 null genotypes with PCOS risk | |||||||
Association of GSTT1 (+) and GSTT1 (−) genotypes with PCOS risk | |||||||
Variables | N = 125 | N = 125 | OR (95% CI) | RR (95% CI) | p value | ||
GSTT1 (+) | 95(76%) | 54 (43.2%) | Ref. 1.00 | Ref. 1.00 | |||
GSTT1 (−) | 30 (24%) | 71 (56.8%) | 4.16 (2.4215 to 7.1589) | 2.14 (1.5532 to 2.9665) | 0.0001 | ||
Association of GSTM1 (+) and GSTM1 (−) genotypes with PCOS risk | |||||||
Variables | N = 125 | N = 125 | OR (95% CI) | RR (95% CI) | |||
GSTM1 (+) | 80 (64%) | 50 (40%) | Ref. 1.00 | Ref. 1.00 | |||
GSTM1 (−) | 45 (36%) | 75 (60%) | 2.66 (1.5992 to 4.4466) | 1.64 (1.2552 to 2.1454) | 0.0002 | ||
Association of GSTT1 (+) GSTM1 (+) and GSTT1 (−) GSTM1 (−) genotypes with PCOS risk | |||||||
Variables | N = 125 | N = 125 | OR (95% CI) | RR (95% CI) | p value | ||
GSTT1 (−) GSTM1 (−) | 42 (33.6%) | 25 (20%) | Ref. 1.00 | Ref. 1.00 | |||
GSTT1 (+) GSTM1 (+) | 33 (26.4%) | 31 (24.8%) | 1.57 (0.7863 to 3.1678) | 1.08 (0.7959 to 1.4820) | 0.19 | ||
Association of GSTT1 (+) GSTM1 (+) and GSTT1 (−) GSTM1 (−) genotypes with PCOS risk | |||||||
Variables | N = 125 | N = 125 | OR (95% CI) | RR (95% CI) | p value | ||
GSTT1 (+) GSTM1 (+) | 33 (21.81%) | 31 (38.18%) | Ref. 1.00 | Ref. 1.00 | |||
GSTT1 (−) GSTM1 (−) | 42 (29.09%) | 25(30%) | 0.63 (0.3157 to 1.2719) | 0.82 (0.6088 to 1.1113) | 0.199 | ||
Association of GSTT1 (+) GSTM1 (−) and GSTT1 (−) GSTM1 (−) genotypes with PCOS risk | |||||||
Variables | N = 125 | N = 125 | OR (95% CI) | RR (95% CI) | p value | ||
GSTT1 (+) GSTM1 (−) | 30 (24%) | 54 (43.2%) | Ref. 1.00 | Ref. 1.00 | |||
GSTT1 (−) GSTM1 (+) | 20 (16%) | 15 (12%) | 0.41 (0.1864 to 0.9316) | 0.62 (0.4165 to 0.9378) | 0.003 |
Subjects | N= | I | ID | D | Df | X2 | I | D | p-Value |
---|---|---|---|---|---|---|---|---|---|
Cases | 125 | 32(25.5%) | 50(40%) | 43(32%) | 2 | 11.38 | 0.58 | 0.52 | 0.0034 |
Controls | 125 | 38(30.4%) | 67(53.6%) | 20(16%) | 0.65 | 0.35 | |||
Association of VEGF-rs699947 C>A gene variation in PCOS cases and controls | |||||||||
Subjects | N= | CC | CA | AA | Df | X2 | C | A | p value |
Cases | 125 | 45(36%) | 54(43.2%) | 26(20.8%) | 2 | 7.58 | 0.58 | 0.42 | 0.020 |
Controls | 125 | 63(50.4%) | 49(39.2%) | 13(10.4%) | 0.70 | 0.30 |
Genotypes | Controls | PCOS Cases | OR (95% CI) | Risk Ratio (RR) | p-Value |
---|---|---|---|---|---|
(N = 125) | (N = 125) | ||||
Codominant inheritance model | |||||
VEGF-(II) | 38 | 32 | 1 (ref.) | 1 (ref.) | |
VEGF-(ID) | 67 | 50 | 0.88 (0.4883 to 1.6084) | 0.94 (0.7266 to 1.2368) | 0.69 |
VEGF-(DD) | 20 | 43 | 2.55 (1.2566 to 5.1874) | 1.71 (1.1223 to 2.6054) | 0.009 |
Dominant inheritance model | |||||
VEGF-(II) | 38 | 32 | 1 (ref.) | 1 (ref.) | |
VEGF-(ID+DD) | 87 | 93 | 1.26 (0.7297 to 2.2084) | 1.12 (0.8636 to 1.4606) | 0.390 |
Recessive inheritance model | |||||
VEGF-(I+ID) | 105 | 82 | 1 (ref.) | 1 (ref.) | |
VEGF-(D) | 20 | 43 | 2.75 (1.5048 to 5.0367) | 1.76 (1.2052 to 2.5957) | 0.001 |
Additive inheritance model (Allele) | |||||
VEGF-(I) | 143 | 112 | 1 (ref.) | 1 (ref.) | |
VEGF-(D) | 107 | 136 | 1.62 (1.1390 to 2.3121) | 1.27 (1.0653 to 1.5226) | 0.007 |
Genotypes | Healthy Controls | PCOS Cases | OR (95% CI) | Risk Ratio (RR) | p-Value |
---|---|---|---|---|---|
(n = 125) | (n = 125) | ||||
Codominant inheritance model | |||||
VEGF-(CC) | 63 | 45 | 1 (ref.) | 1 (ref.) | |
VEGF-(CA) | 49 | 54 | 1.54 (0.8955 to 2.6580) | 1.22 (0.947 to 1.586) | 0.11 |
VEGF-(AA) | 13 | 26 | 2.80 (1.2992 to 6.0344) | 1.75 (1.092 to 2.804) | 0.008 * |
Dominant inheritance model | |||||
VEGF-(CC) | 63 | 45 | 1 (ref.) | 1 (ref.) | |
VEGF-(CA + AA) | 62 | 80 | 1.80 (1.0888 to 2.9971) | 1.33 (1.0451 to 1.7079) | 0.022 * |
Recessive inheritance model | |||||
VEGF-(CC + CA) | 112 | 99 | 1 (ref.) | 1 (ref.) | |
VEGF-(AA) | 13 | 26 | 2.26 (1.1029 to 4.6418) | 1.59 (1.0036 to 2.5266) | 0.025 * |
Additive inheritance model (Allele) | |||||
VEGF-(C) | 175 | 144 | 1 (ref.) | 1 (ref.) | |
VEGF-(A) | 75 | 106 | 1.71 (1.1877 to 2.483) | 1.32 (1.0842 to 1.6167) | 0.004 * |
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Almotairi, R.; Mir, R.; Almasoudi, K.S.; Husain, E.; Mtiraoui, N. Evaluating the Impact of rs4025935, rs71748309, rs699947, and rs4646994 Genetic Determinants on Polycystic Ovary Syndrome Predisposition—A Case-Control Study. Life 2025, 15, 558. https://doi.org/10.3390/life15040558
Almotairi R, Mir R, Almasoudi KS, Husain E, Mtiraoui N. Evaluating the Impact of rs4025935, rs71748309, rs699947, and rs4646994 Genetic Determinants on Polycystic Ovary Syndrome Predisposition—A Case-Control Study. Life. 2025; 15(4):558. https://doi.org/10.3390/life15040558
Chicago/Turabian StyleAlmotairi, Reema, Rashid Mir, Kholoud S. Almasoudi, Eram Husain, and Nabil Mtiraoui. 2025. "Evaluating the Impact of rs4025935, rs71748309, rs699947, and rs4646994 Genetic Determinants on Polycystic Ovary Syndrome Predisposition—A Case-Control Study" Life 15, no. 4: 558. https://doi.org/10.3390/life15040558
APA StyleAlmotairi, R., Mir, R., Almasoudi, K. S., Husain, E., & Mtiraoui, N. (2025). Evaluating the Impact of rs4025935, rs71748309, rs699947, and rs4646994 Genetic Determinants on Polycystic Ovary Syndrome Predisposition—A Case-Control Study. Life, 15(4), 558. https://doi.org/10.3390/life15040558