Abstract
BACKGROUND AND OBJECTIVE: Females with sickle cell disease (SCD) often show late onset of menarche. In transgenic sickle cell mouse, deficiency of gene encoding endothelial nitric oxide synthase (eNOS) has been reported to be associated with late onset of menarche. Thus to explore the possible association of eNOS gene polymorphism with age of onset of menarche in SCD females, 3 important eNOS gene polymorphisms- eNOS 4a/b, eNOS 894G>T (rs1799983) and eNOS-786 T>C (rs2070744) and plasma nitrite levels were tested among three groups of females- SCD late menarche, SCD early menarche and control females. METHODOLOGY: About 39 SCD females comprising of 18 SCD early menarche and 21 SCD late menarche groups were studied along with 48 control females. Genotyping of eNOS gene polymorphisms were done by PCR-RFLP and quantification of plasma nitrite level was performed by ELISA based commercial kits. RESULTS: SCD late menarche females showed significantly higher prevalence and higher association of heterozygous genotypes, higher frequency of mutant alleles .4a., .T. and .C. as compared to that of control group and SCD early menarche group. The frequency of haplotype .4a-G-C. and haplotype .4b-G-C. (alleles in order of eNOS 4a/b, eNOS 894G>T and eNOS-786 T>C respectively) were found to be significantly high in SCD late menarche compared to combined groups of SCD early menarche and controls. SCD late menarche group had significantly low level of plasma nitrite concentration for all 3 eNOS gene polymorphisms as compared to controls and SCD early menarche females. CONCLUSION: eNOS gene polymorphism may influence age of onset of menarche in SCD females.