Table 2 Genetic Variants Associated with POI
| Mechanism | Gene | Subject Demographics | Subject Sample Size & Selection Criteria | Variant Frequency | Reference |
|---|---|---|---|---|---|
| Follicle Development | NOBOX |
Caucasian, Senegalese, Bantu [81] Caucasian, African [82] |
178 women diagnosed with idiopathic POI and 362 ethnic-matched women control [81] 213 women diagnosed with idiopathic POI and 362 ethnic-matched women control [82] |
6.2% in POI group 0% in control group [81] 7% in POI group 0% in control group [82] | [81, 82] |
| FIGLA | Chinese | 100 women diagnosed with POI and 304 healthy women between 30 and 62 years old with regular menses and no history of infertility as control |
4% in POI group 0.3% in control group | [83] | |
| BNC1 | Chinese | 82 women diagnosed with POI and 332 healthy female control |
4% in POI group 0% in control group | [84] | |
| SOHLH1 | China, Serbia |
364 Chinese women and 197 Serbian women diagnosed with POI 400 Chinese and 200 Serbian women with regular menses and normal FSH level as control |
2.2% in Chinese POI group 0.9% in Chinese control group 0% in Serbian POI group 0% in Serbian control group | [85] | |
| SOHLH2 | China, Serbia |
364 Chinese women and 197 Serbian women diagnosed with POI; 222 Chinese and 200 Serbian women with normal menses and normal FSH level as control |
2.2% Chinese POI group 0% in Chinese control group 2% in Serbian POI group 0% in Serbian control group | [86] | |
| FOXO3A/FOXO1A |
China, New Zealand, Slovenia |
114 Chinese patients diagnosed with POI and 100 control subjects under the age of 40 with proven fertility, normal menstrual cycle and ovarian morphology [87] 30 patients from New Zealand and 60 patients from Slovenia diagnosed with POI and 60 healthy control subjects [69] |
13% in POI group (FOXO3) 0% in control group (FOXO3) [87] 2.2% in POI group (FOXO3A) 0% in control group (FOXO3A) 1.1% in POI group (FOXO1A) 0% in control group (FOXO1A) [69] | [69, 87] | |
| Follicle Development | BMP15 | US (Caucasian) | 166 Caucasian women diagnosed with POI and 211 controls (95 women with menopause beyond 50 years of age, 86 women and 30 men from the general population) |
2.1% in POI group 0% in control | [88] |
|
KHDRBS1 (or Sam68) | Chinese | 215 women diagnosed with POI and 400 women over age of 40 not diagnosed with POI with a history of regular menstrual cycle |
0.04% in POI group 0% in control group | [89] | |
|
FMR1 Premutation (55–200 CGG repeats) | Unknown | UK | 254 women presented with POI and 1915 controls selected either as postmenopausal at entry with a menopausal age of 46 years or older (74.3%) or premenopausal and entered the study at 46 years or older (25.7%) |
2% in POI group 0.4% in control group | [90] |
|
DNA Damage Repair | BRCA1 | UK |
2028 women diagnosed with breast cancer before age of 55 between 1991 and 1996 prevalence calculated based on a mathematical model |
1.2% in cancer group; 0.09% in general population | [91] |
| MCM8/9 | US |
155 women diagnosed with POI Control group data from public database such as exome variant server |
2% in POI group (MCM8) 0% in control group (MCM8) 5% in POI group (MCM9) 0% in control group (MCM9) | [92] | |
| FANCM | Chinese | 200 patients diagnosed with POI and 200 age-matched women with regular menses an normal FSH level as control |
0.4% in POI group 0% in control group | [93] | |
| Apoptosis Regulation | NANOS3 | Chinese, Caucasian, Brazilian |
80 Chinese women and 88 Caucasian women diagnosed with POI and 63 healthy Chinese and 63 healthy Caucasian control subjects [94] 30 Brazilian women diagnosed with POI and 185 women with normal fertility as control [95] |
0.14% in Chinese POI group 0.09% in Chinese control group 0.09% in Caucasian POI group 0.03% in Caucasian control group [94] 0% in POI group 0% in control group [95] | [94, 95] |
| PGRMC1 | China | 196 nulligravida women diagnosed with POI without family history of POI or X chromosome abnormalities and 200 healthy women with regular menstrual cycle and no known history of infertility before age of 40 years |
0.51% in POI group 0% in control group | [96] | |
| HFM1 | Meiosis | Chinese | 69 women diagnosed with POI and 316 controls matched for ethnic background, sex and age |
2.9% in POI group 0% in control group | [97] |