rs743572 — CYP17A1 -34 T>C

CYP17A1 -34 T>C: Master Regulator of Steroid Hormone Production

The CYP17A1 gene encodes 17α-hydroxylase/17,20-lyase, a dual-function enzyme essential for synthesizing all steroid hormones except aldosterone. This enzyme sits at a critical junction in the steroid pathway¹¹ This enzyme sits at a critical junction in the steroid pathway
CYP17A1 converts pregnenolone and progesterone to their 17α-hydroxylated forms, which are then used to make cortisol, or cleaved to produce DHEA, the precursor for testosterone and estrogen. The rs743572 variant lies in the gene's promoter region, 34 base pairs upstream of the translation start site.

The Mechanism

This T>C substitution creates a binding site for the Sp1 transcription factor when the C allele is present. Sp1 is a transcriptional activator²² Sp1 is a transcriptional activator
The additional Sp1 binding site created by the C allele may increase CYP17A1 gene expression, leading to elevated enzyme levels and potentially higher androgen synthesis. The variant affects gene expression rather than protein structure, with downstream effects on the entire steroid hormone cascade.

Located in the 5' untranslated region on chromosome 10, this regulatory variant demonstrates how small changes in gene expression control can have broad metabolic effects. The degree of functional impact appears to vary by tissue type and hormonal milieu, with effects most pronounced in steroidogenic tissues like the adrenal cortex, ovarian theca cells, and testicular Leydig cells.

The Evidence

A 2021 meta-analysis of 15 studies encompassing 2,277 PCOS patients and 1,913 controls found that the CC genotype was associated with increased PCOS risk under a recessive model (OR 1.24, 95% CI 1.02-1.50)³³ A 2021 meta-analysis of 15 studies encompassing 2,277 PCOS patients and 1,913 controls found that the CC genotype was associated with increased PCOS risk under a recessive model (OR 1.24, 95% CI 1.02-1.50)
This association was stronger in Caucasian women (OR 1.45, 95% CI 1.03-2.06) than in Asian populations. Polycystic ovary syndrome is characterized by hyperandrogenism, menstrual irregularity, and metabolic dysfunction affecting 5-10% of reproductive-aged women.

A 2024 Chinese study of men with benign prostatic hyperplasia found that the GG genotype (equivalent to CC on the forward strand) was independently associated with metabolic syndrome and BPH, with a decreased testosterone-to-estradiol ratio⁴⁴ A 2024 Chinese study of men with benign prostatic hyperplasia found that the GG genotype (equivalent to CC on the forward strand) was independently associated with metabolic syndrome and BPH, with a decreased testosterone-to-estradiol ratio
The GG genotype showed an OR of 5.87 for BPH and 7.23 for metabolic syndrome after age adjustment. This suggests the variant's effects extend beyond reproductive disorders to metabolic health in both sexes.

A case-control study of 143 endometriosis patients found the TT genotype associated with 1.95-fold increased endometriosis risk⁵⁵ A case-control study of 143 endometriosis patients found the TT genotype associated with 1.95-fold increased endometriosis risk
The association remained significant after adjusting for confounding factors. However, results have been mixed across different populations and conditions.

Notably, a large Australian study of 824 prostate cancer cases found no association between rs743572 and prostate cancer risk or circulating hormone levels (testosterone, estradiol, DHEA-S, androstenedione)⁶⁶ a large Australian study of 824 prostate cancer cases found no association between rs743572 and prostate cancer risk or circulating hormone levels (testosterone, estradiol, DHEA-S, androstenedione)
Men with different genotypes had similar hormone levels across all measures tested. This negative finding suggests the variant's effects may be context-dependent or limited to specific tissues.

Practical Implications

This variant's primary clinical significance relates to hormone-dependent conditions, particularly PCOS in women and metabolic syndrome in men. The CC genotype appears to shift steroid hormone balance toward increased androgen production, though the magnitude varies substantially by individual, tissue, and hormonal environment.

For women with PCOS symptoms (irregular periods, hirsutism, acne, infertility), the CC genotype may indicate a genetic predisposition to androgen excess. However, PCOS is multifactorial, and this variant is neither necessary nor sufficient for disease development. Management focuses on insulin sensitization (metformin, lifestyle modification), hormonal contraceptives for symptom control, and fertility treatments when needed.

For men, particularly those with metabolic syndrome, the variant may contribute to altered testosterone-to-estradiol ratios. Maintaining a healthy weight, regular exercise, and metabolic health monitoring become especially important. The association with BPH suggests monitoring prostate health with age may be warranted for CC carriers with metabolic risk factors.

The variant does not appear to affect response to CYP17A1 inhibitors like abiraterone, which are used in castration-resistant prostate cancer treatment. Circulating hormone levels are influenced by many factors beyond this single variant, so testing should be based on clinical symptoms rather than genotype alone.

Interactions

This variant functions within the broader steroid hormone synthesis pathway. Other variants in genes encoding enzymes downstream of CYP17A1—such as CYP19A1 (aromatase, converting androgens to estrogens), HSD3B1 (converting DHEA to androstenedione), and SRD5A2 (converting testosterone to DHT)—may compound or modify the effects of CYP17A1 variants. However, specific gene-gene interactions for rs743572 have not been systematically studied in the literature.