Two different human LH receptor sequences have been published, differing by a 6-basepair insertion encoding leu-gln at position 55-60 (Minegishi et al., 1990; Atger et al., 1995). Rodien et al. (1998) demonstrated that both sequences exist as allelic variants in the Caucasian population. Allele frequencies of LQ variant and wildtype allele are 0.26 and 0.74 respectively. In contrast, the LQ allele is virtually absent from the Japanese population. Functional characterization of both alleles by transient expression in COS-7 cells did not reveal any difference between the 2 receptors, neither for cell surface expression nor for cAMP production and sensitivity to CG/LH.
Powell et al. (2003) investigated whether functional polymorphic variants in the LH signaling pathway are associated with the risk of breast cancer or its clinical phenotype. Women who were homozygous for the LQ allele were, on average, 8.3 years younger at diagnosis, compared with those homozygous for the wildtype LHR allele (mean age, 51.9 years vs 60.2 years; P = 0.03). Trends were observed for associations between LQ carriers and nodal involvement or larger tumor size. Patients who were LQ carriers revealed a significantly worse overall survival, compared with those who were homozygous for wildtype LHR. The authors concluded that their findings suggested that the LQ gene polymorphism determines an earlier age of disease onset and is prognostic for poor outcome of breast cancer.
