A common protamine 1 promoter polymorphism (-190 C→{A) correlates with abnormal sperm morphlogy and increased protamine P1/P2 ratio in infertile patients

Abstract

It is known that targeting the protamine 1 gene in mice leads to infertility, abnormal chromatin packaging, and abnormal sperm morphology. Because many infertile patients also have an abnormal sperm morphology and chromatin packaging, the human protamine 1 gene (PRM1) is an important candidate to screen for potential mutations. In this work, we have screened the PRM1 gene in search of potential mutations and determined the sperm morphology and the ratio between protamine 1 and protamine 2 (P1/P2 ratio). Direct sequencing of the PRM1 promoter led to the identification of a common single-nucleotide polymorphism (SNP; -190 C→A). The -190 AA genotype was detected at a higher frequency (13.8%) in patients with markedly altered sperm morphology (≤9% normal forms) compared with other patients (4.5%; P < .05) or compared with controls (2.97%; P < .005). The allelic frequency of the PRM1 -190 C→A change was also consistently higher (.331) in infertile patients with a markedly altered morphology compared with population controls (.178; P