Triple CGG counts on the FMR1 (Fragile X) gene vary between races/ethnicities based on distribution, but not based on normal range and median

Abstract

OBJECTIVE: 26-32 CGG repeats on the FMR1 gene reflect normal, while < 26 and >32 denote risk towards diminished ovarian reserve (DOR). Whether CGG counts differ between different races/ethnicities was recently by an NIH panel identified as a desirable research subject.DESIGN: Cohort study.MATERIALS AND METHODS: 385 consecutive females with FMR1 results (770 alleles), who identified as belonging to a single race/ethnicity, were studied and classified (as self identified) Caucasian, African or Asian (women in three other ethnicities co-identified as Hispanic). Box and whisker plots were established, defining the normal range of CGG repeats for each race/ethnicity and distribution of outliers (CGG counts outside of normal range) was compared.RESULTS: Box and whisker plots confirmed 26-32 CGG counts (median 30) as normal range for all patients, and reconfirmed this range within each race/ethnic group. African and Asian women demonstrated, more homogeneity in CGG counts than Caucasians: Asians demonstrated a higher prevalence of two normal range allele counts (65.0%) than Caucasians (54.3%; p=0.03); Caucasians demonstrated the highest rate of abnormal allele counts (43.3%) and were the only racial/ethnic group demonstrating homozygous (both allele) abnormalities. In contrast, Asian women are genetically most homogenous and demonstrated significantly fewer lower outliers (<26 repeats) than Caucasians (p=0.002) and Africans (p=0.03).CONCLUSIONS: These data suggest that: [1] 26-32 (median 30) CGG counts on the FMR1 gene represent the normal range in reference to ovarian reserve, independent of race/ethnicity. [2] This finding also, in principle, validates this normal range. [3] Races/ethnicities, however, nevertheless differ significant in the distribution of triple CGG counts, with Asians being most, and Caucasians least, homogeneous; [4] These differences may reflect differences in ovarian function and female fertility, as have been reported in the literature. OBJECTIVE: 26-32 CGG repeats on the FMR1 gene reflect normal, while < 26 and >32 denote risk towards diminished ovarian reserve (DOR). Whether CGG counts differ between different races/ethnicities was recently by an NIH panel identified as a desirable research subject. DESIGN: Cohort study. MATERIALS AND METHODS: 385 consecutive females with FMR1 results (770 alleles), who identified as belonging to a single race/ethnicity, were studied and classified (as self identified) Caucasian, African or Asian (women in three other ethnicities co-identified as Hispanic). Box and whisker plots were established, defining the normal range of CGG repeats for each race/ethnicity and distribution of outliers (CGG counts outside of normal range) was compared. RESULTS: Box and whisker plots confirmed 26-32 CGG counts (median 30) as normal range for all patients, and reconfirmed this range within each race/ethnic group. African and Asian women demonstrated, more homogeneity in CGG counts than Caucasians: Asians demonstrated a higher prevalence of two normal range allele counts (65.0%) than Caucasians (54.3%; p=0.03); Caucasians demonstrated the highest rate of abnormal allele counts (43.3%) and were the only racial/ethnic group demonstrating homozygous (both allele) abnormalities. In contrast, Asian women are genetically most homogenous and demonstrated significantly fewer lower outliers (<26 repeats) than Caucasians (p=0.002) and Africans (p=0.03). CONCLUSIONS: These data suggest that: [1] 26-32 (median 30) CGG counts on the FMR1 gene represent the normal range in reference to ovarian reserve, independent of race/ethnicity. [2] This finding also, in principle, validates this normal range. [3] Races/ethnicities, however, nevertheless differ significant in the distribution of triple CGG counts, with Asians being most, and Caucasians least, homogeneous; [4] These differences may reflect differences in ovarian function and female fertility, as have been reported in the literature.