Pyun Jung-A, Kim Sunshin, Cha Dong Hyun, Kwack KyuBum
From the 1Department of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea; and 2Division of Genetics, Department of Obstetrics and Gynecology, College of Medicine, CHA General Hospital, CHA University, Seoul, Republic of Korea.
Menopause. 2014 Aug;21(8):890-5. doi: 10.1097/GME.0000000000000172.
This study investigated whether epistasis between single nucleotide polymorphisms (SNPs) within the TSHB (thyroid-stimulating hormone β) and ADAMTS16 (ADAM metallopeptidase with thrombospondin type 1 motif, 16) genes is associated with an increased risk of premature ovarian failure (POF) in Korean women.
In stage I, 120 women with POF and 222 controls participated. A GoldenGate assay with VeraCode technology was used to genotype SNPs within the TSHB and ADAMTS16 genes. For stage II, we obtained genotype data merged with imputed data for 1,641 female controls from the Korean Genome Epidemiology Study.
In stage I, two SNPs (rs7530810 and rs1321108) in the 5' flanking region of the TSHB gene demonstrated significant synergistic interactions with one tagging intronic SNP (rs13172105) in the ADAMTS16 gene (odds ratios, 6.63 and 5.57; 95% CIs, 2.30-19.18 and 2.05-15.12; P = 0.00048 and 0.00074, respectively) although the SNPs were not significantly associated with POF in a single SNP model. When at least one G allele at rs7530810 or one A allele at rs1321108 was present in combination with a C allele at rs13172105, significant synergistic effects were observed in a recessive model. In stage II and combined analyses, the same combinations repeatedly showed significant synergistic interactions.
Epistasis between SNPs within the TSHB and ADAMTS16 genes may increase the risk of POF in Korean women.
本研究调查了促甲状腺激素β（TSHB）基因和含血小板反应蛋白基序的解聚素样金属蛋白酶16（ADAMTS16）基因内单核苷酸多态性（SNP）之间的上位性是否与韩国女性卵巢早衰（POF）风险增加相关。
在第一阶段，120例POF女性和222例对照参与研究。采用VeraCode技术的GoldenGate检测法对TSHB和ADAMTS16基因内的SNP进行基因分型。在第二阶段，我们从韩国基因组流行病学研究中获得了1641名女性对照的基因分型数据以及合并的推算数据。
在第一阶段，TSHB基因5'侧翼区域的两个SNP（rs7530810和rs1321108）与ADAMTS16基因中的一个标签内含子SNP（rs13172105）表现出显著的协同相互作用（优势比分别为6.63和5.57；95%可信区间分别为2.30 - 19.18和2.05 - 15.12；P值分别为0.00048和0.00074），尽管在单SNP模型中这些SNP与POF无显著关联。当rs7530810处至少一个G等位基因或rs1321108处至少一个A等位基因与rs13172105处的一个C等位基因同时存在时，在隐性模型中观察到显著的协同效应。在第二阶段及合并分析中，相同组合反复显示出显著的协同相互作用。
TSHB和ADAMTS16基因内SNP之间的上位性可能增加韩国女性患POF的风险。
