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Background <p>Impaired angiogenesis and hypoxia may be involved in infertility, a serious reproductive disorder. <i>VEGF</i> and <i>HIF1A</i> regulate these processes; therefore, genetic variants in these genes serve as candidates for the assessment of infertility risk. The aim of the study was to investigate the association of three <i>VEGF</i> promoter [− 2578C/A (rs699947), − 2549I/D (rs35569394), − 460&#xa0;T/C (rs833061)] and three <i>HIF1A</i> exonic [g.C1772T (rs11549465), g.G1790A (rs11549467) and g.C111A] polymorphisms with infertility risk in patients from Punjab, North India.</p> Methods <p>In this case–control study, 193 clinically confirmed infertile patients and 213 age and gender matched healthy controls were investigated. <i>VEGF</i> − 2578C/A, − 460&#xa0;T/C, <i>HIF1A g.</i>C1772T, g.G1790A and g.C111A polymorphisms were genotyped using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR–RFLP) whereas genotyping of <i>VEGF</i>-2549I/D polymorphism was done using the direct-PCR.</p> Results <p><i>VEGF</i>-2549II genotype and I allele, <i>VEGF</i>-2578AA genotype and <i>VEGF</i>-460CC genotypes were significantly associated with increased risk to infertility. Analysis of the data under different genetic models revealed a significantly increased risk under co-dominant (<i>p</i> = 0.02), recessive (<i>p</i> = 0.02) and log additive model (<i>p</i> = 0.03) for <i>VEGF</i>-2549I/D polymorphism whereas <i>VEGF</i>-2578C/A polymorphism was associated with increased risk under co-dominant (<i>p</i> = 0.03) and recessive (<i>p</i> = 0.03) genetic models. <i>VEGF</i>-460&#xa0;T/C polymorphism was associated with increased risk under co-dominant (<i>p</i> = 0.04) and recessive model (<i>p</i> = 0.04) only. For <i>HIF1A</i> g.G1790A and <i>HIF1A</i> g.C111A polymorphisms, all the patients and controls had GG and CC genotypes respectively. There was no significant difference in the genotype frequency between patients and controls for <i>HIF1A</i> g.C1772T polymorphism.</p> Conclusion <p>This study suggests that <i>VEGF</i> − 2578C/A, − 2549I/D and − 460&#xa0;T/C polymorphisms were associated with increased risk of infertility in the patients from Punjab, North India.</p>

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VEGF and HIF1A polymorphisms and infertility risk in North-West Indians: a case- control study

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  • 发表日期：

    2025年9月10日

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  • Vasudha Sambyal,
  • Deepanshi Mahajan,
  • Kamlesh Guleria

摘要

Background

Impaired angiogenesis and hypoxia may be involved in infertility, a serious reproductive disorder. VEGF and HIF1A regulate these processes; therefore, genetic variants in these genes serve as candidates for the assessment of infertility risk. The aim of the study was to investigate the association of three VEGF promoter [− 2578C/A (rs699947), − 2549I/D (rs35569394), − 460 T/C (rs833061)] and three HIF1A exonic [g.C1772T (rs11549465), g.G1790A (rs11549467) and g.C111A] polymorphisms with infertility risk in patients from Punjab, North India.

Methods

In this case–control study, 193 clinically confirmed infertile patients and 213 age and gender matched healthy controls were investigated. VEGF − 2578C/A, − 460 T/C, HIF1A g.C1772T, g.G1790A and g.C111A polymorphisms were genotyped using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR–RFLP) whereas genotyping of VEGF-2549I/D polymorphism was done using the direct-PCR.

Results

VEGF-2549II genotype and I allele, VEGF-2578AA genotype and VEGF-460CC genotypes were significantly associated with increased risk to infertility. Analysis of the data under different genetic models revealed a significantly increased risk under co-dominant (p = 0.02), recessive (p = 0.02) and log additive model (p = 0.03) for VEGF-2549I/D polymorphism whereas VEGF-2578C/A polymorphism was associated with increased risk under co-dominant (p = 0.03) and recessive (p = 0.03) genetic models. VEGF-460 T/C polymorphism was associated with increased risk under co-dominant (p = 0.04) and recessive model (p = 0.04) only. For HIF1A g.G1790A and HIF1A g.C111A polymorphisms, all the patients and controls had GG and CC genotypes respectively. There was no significant difference in the genotype frequency between patients and controls for HIF1A g.C1772T polymorphism.

Conclusion

This study suggests that VEGF − 2578C/A, − 2549I/D and − 460 T/C polymorphisms were associated with increased risk of infertility in the patients from Punjab, North India.