Why do fragile X carrier frequencies differ between Asian and non-Asian populations?

Genereux, Diane P.; Laird, Charles D.

doi:10.1266/ggs.88.211

Cited by 12 publications

(11 citation statements)

References 47 publications

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“…22 The Asian curve was left-shifted, which indicated a lower mean repeat length for intermediate and expanded alleles among Asians. The study by Otsuka et al 19 might suggest potentially an overall lower distribution at repeats <40 CGG in Japanese populations, given their finding of a slightly lower modal value than reported elsewhere (Table 1).…”

Section: Existing Population Data On Fmr1 Differences By Race-ethnicitymentioning

confidence: 99%

FMRI CGG Repeats:Reference Levels and Race-Ethnic Variation in Women With Normal Fertility (Study of Women’s Health Across the Nation)

et al. 2016

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, and potentially women with high normal (35)(36)(37)(38)(39)(40)(41)(42)(43)(44) or low normal (<28) CGG repeats, are at risk of premature ovarian aging. The scarcity of population data on CGG repeats <45 CGG, and variation in raceethnicity, makes it difficult to determine true associations. DNA was analyzed for FMR1 CGG repeat lengths from 803 women (386 caucasians, 219 African Americans, 102 Japanese, and 96 Chinese) from the US-based Study of Women's Health Across the Nation (SWAN). Participants had 1 menses in the 3 months before enrollment, 1 pregnancy, no history of infertility or hormonal therapy, and menopause 46 years. Statistical analyses used Fisher exact tests. Among these women with normal reproductive histories, significant FMR1 repeat length differences were found across race-ethnicity for both the longer (P ¼ .0002) and the shorter (P < .0001) alleles. The trinucleotide length variance was greater for non-Asian than Asian women (P < .0001), despite identical median values. Our data indicate that short allele lengths <25 CGG on one or both alleles are more common in non-Asian than Asian women. We confirm the minor allele in the 35 to 39 CGG range among Asians as reported previously. Only 2 (0.3%) premutation carriers were identified. These data demonstrate that FMR1 distributions do vary by race-ethnicity, even within the ''normal'' range. This study indicates the need to control for race-ethnicity in FMR1 ovarian aging research and provides race-ethnic population data for females separated by allele.

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Section: Existing Population Data On Fmr1 Differences By Race-ethnicitymentioning

confidence: 99%

FMRI CGG Repeats:Reference Levels and Race-Ethnic Variation in Women With Normal Fertility (Study of Women’s Health Across the Nation)

et al. 2016

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“…There is no consensus about the estimated prevalence of FMR1 alleles and this prevalence varies between geographical areas and the population assessed [41,44,45]. …”

Section: Fmr1 Genementioning

confidence: 99%

Study of the Genetic Etiology of Primary Ovarian Insufficiency: FMR1 Gene

Barasoain

Barrenetxea

Huerta

et al. 2016

Genes

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Menopause is a period of women’s life characterized by the cessation of menses in a definitive way. The mean age for menopause is approximately 51 years. Primary ovarian insufficiency (POI) refers to ovarian dysfunction defined as irregular menses and elevated gonadotrophin levels before or at the age of 40 years. The etiology of POI is unknown but several genes have been reported as being of significance. The fragile X mental retardation 1 gene (FMR1) is one of the most important genes associated with POI. The FMR1 gene contains a highly polymorphic CGG repeat in the 5′ untranslated region of exon 1. Four allelic forms have been defined with respect to CGG repeat length and instability during transmission. Normal (5–44 CGG) alleles are usually transmitted from parent to offspring in a stable manner. The full mutation form consists of over 200 repeats, which induces hypermethylation of the FMR1 gene promoter and the subsequent silencing of the gene, associated with Fragile X Syndrome (FXS). Finally, FMR1 intermediate (45–54 CGG) and premutation (55–200 CGG) alleles have been principally associated with two phenotypes, fragile X tremor ataxia syndrome (FXTAS) and fragile X primary ovarian insufficiency (FXPOI).

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“…One of the important limitations of this study concerns the lack of analyses stratified by other related susceptible factors, such as race and ethnicity have not been conducted in the present study because insufficient data were available from the primary studies. Race/ethnic differences in the FMR1 CGG repeat distribution have been reported [37][38][39]. However, the results from individual studies were inconsistent.…”

Section: Discussionmentioning

confidence: 99%

“…However, the results from individual studies were inconsistent. Genereux and Laird used eight general population studies and found that the Asian and non-Asian populations had similar distribution curves, but the Asian curve was leftshifted and "almost completely non-overlapping" relative to the non-Asian distribution [38]. A study performed by Pastore et al [18] found that DOR cases had fewer CGG repeats in the shorter FMR1 allele than controls among Whites, but this was not significant among Asians.…”

Section: Discussionmentioning

confidence: 99%

Association between the FMR1 CGG repeat lengths and the severity of idiopathic primary ovarian insufficiency: a meta analysis

Huang

Zhang

Liu³

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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2019) Association between the FMR1 CGG repeat lengths and the severity of idiopathic primary ovarian insufficiency: a meta analysis, Artificial Cells, Nanomedicine, and Biotechnology, 47:1, 3116-3122, ABSTRACT Aim: Reports on the association of the CGG repeat length in the FMR1 gene with the severity of idiopathic POI are inconclusive. Therefore, a meta analysis was performed to investigate the relationship between the expansion of repeat CGG and idiopathic POI risk. Methods: Up to January 2019, 18 case-control or cohort studies involving 3022 idiopathic POI patients and 8461 controls were included for meta analysis. Results: Thirteen studies, including 2047 cases and 6912 controls, met our criteria for the assessment of the premutation and intermediate repeat length in patients patients with POI. Compared with controls, FMR1 gene premutation is significantly associated with POI (OR ¼ 8.13; 95% CI: 4.35-15.19; p < .00001), whereas there was no significant correlation between intermediate repeat length and POI (OR ¼ 0.86; 95% CI: 0.62-1.18; p ¼ .34). Six studies, representing 975 patients and 1749 controls, were eligible for evaluation of the premutation and intermediate repeat length in diminished ovarian reserve (DOR). The association between premutation and DOR was significant (OR¼14.87; 95% CI:5.20-42.52; p < 0.00001), while no significant correlation of intermediate size to DOR was found in the case-control comparison (OR ¼ 0.98; 95% CI: 0.65-1.47; p ¼ 0.93). Conclusion: There is a close association between premutation of the FMR1 gene and increased susceptibility to idiopathic POI of each stage and no correlation between intermediate repeat length of the FMR1 gene and the severity of idiopathic POI. ARTICLE HISTORY KEYWORDSIdiopathic primary ovarian insufficiency; diminished ovarian reserve, fragile X mental retardation 1 (FMR1); CGG repeat length; meta analysis CONTACT Hong Jiang

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Why do fragile X carrier frequencies differ between Asian and non-Asian populations?

Cited by 12 publications

References 47 publications

FMRI CGG Repeats:Reference Levels and Race-Ethnic Variation in Women With Normal Fertility (Study of Women’s Health Across the Nation)

FMRI CGG Repeats:Reference Levels and Race-Ethnic Variation in Women With Normal Fertility (Study of Women’s Health Across the Nation)

Study of the Genetic Etiology of Primary Ovarian Insufficiency: FMR1 Gene

Association between the FMR1 CGG repeat lengths and the severity of idiopathic primary ovarian insufficiency: a meta analysis

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