Androgen receptor polymorphism (CAG repeats) and androgenicity

Area of Science:

• Genetics
• Endocrinology
• Human Physiology

Background:

• Androgen receptor (AR) gene polymorphism, specifically CAG repeats (CAGr), is linked to various health conditions.
• Understanding AR polymorphism distribution is crucial for interpreting its role in androgen-related disorders.

Purpose of the Study:

• To determine the frequency distribution of AR CAG repeats in a healthy Italian population.
• To investigate the association of AR CAG repeats with hypoandrogenism and infertility.

Main Methods:

• Direct sequencing was used to analyze CAG repeat lengths in 91 healthy controls, 29 hypoandrogenic patients, and 29 infertile patients.
• Statistical analysis compared CAG repeat distributions across the groups.

Main Results:

• Hypoandrogenic males exhibited a statistically significant shift towards longer CAG repeats (mean 24.0) compared to controls (mean 21.5) and infertile patients (mean 21.4).
• 38% of hypoandrogenic patients had 25 or more CAG repeats, versus 5% in controls and 7% in infertile patients.
• No significant difference in CAG repeat length was found between infertile patients and controls. CAGr length did not correlate with hormonal levels but showed slight correlation with testis and prostate volume in hypoandrogenic subjects.

Conclusions:

• The AR CAG repeat distribution in the Italian population is comparable to other European populations.
• Longer AR CAG repeats are associated with hypoandrogenism, suggesting a role in modulating androgenic effects.
• AR polymorphism, rather than circulating testosterone levels alone, influences the final androgenic phenotype in conditions like hypoandrogenism.