Evidence that luteinising hormone receptor polymorphisms may contribute to male undermasculinisation

Abstract

Background: The luteinising hormone receptor (LHR) is necessary for the stimulation of androgen production and male genital development. It contains three protein polymorphisms: a leucine and glutamine insertion between codons 8 and 9 (LQ+) and two amino acid substitutions (N291S, N312S). Objectives: To determine whether these LHR polymorphisms are associated with male genital under-masculinisation or the androgen receptor polyglutamine repeat polymorphism (AR(Q)n), which contributes in some cases to the cause of genital undermasculinisation. Methods: The LHR polymorphisms were assessed by PCR amplification of genomic DNA, followed by restriction enzyme analysis. The frequency of the LHR polymorphisms were compared between an undermasculinised male group (n = 75) and a control group (n = 55). Results: LQ+ was not independently associated with the undermasculinised group (P = 0.09), but it was associated with increased AR(Q)n within the undermasculinised group (P = 0.02), particularly for AR(Q)n lengths ≥ 26 (P = 0.002). In the undermasculinised group, homozygosity for N291 (872A/A) was more frequent (P = 0.05), whereas homozygosity for N312 (935A/A) was less frequent (P = 0.05). The combination of the presence of 872A/A and the absence of 935A/A showed a stronger association with the undermasculinised group than either polymorphism independently (P = 0.006). The odds ratio of this genotype compared with any other, between the undermasculinised and control groups was 3.28 (95% confidence interval (CI) 1.33 to 8.08). Conclusion: LHR polymorphisms may contribute to genital undermasculinisation.