FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome.
FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome.
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DOI：
10.1371/journal.pone.0016390
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发表时间：
2011-01-20
期刊：
影响因子：
3.7
通讯作者：
Strauss JF 3rd
中科院分区：
文献类型：
--
作者：
Ewens KG;Jones MR;Ankener W;Stewart DR;Urbanek M;Dunaif A;Legro RS;Chua A;Azziz R;Spielman RS;Goodarzi MO;Strauss JF 3rd
多囊卵巢综合征(PCOS)是女性无排卵性不孕的主要原因。它还与代谢紊乱有关，这些代谢紊乱使女性患肥胖症和2型糖尿病的风险增加。有强有力的证据表明多囊卵巢综合征的家族聚集性和遗传易感性。然而，导致多囊卵巢综合征表型的基因(S)尚不清楚。这项基于家庭和病例对照的两阶段遗传学研究旨在解决在全基因组关联研究中被确定为肥胖易感基因的SNP是否也与多囊卵巢综合征和BMI升高相关。对至少有一个孩子患有多囊卵巢综合征的439个家庭的成员进行了15个SNP的基因分型，这些SNP以前被证明与肥胖有关。用传递/不平衡检验(TDT)评估与多囊卵巢综合征的连锁和关联。这些SNP还在一项独立的病例对照研究中进行了分析，研究对象包括395名患有多囊卵巢综合征的女性和176名有规律月经周期的健康女性。这15个SNP中只有一个(NEGR1中的rs2815752)被发现与多囊卵巢综合征有名义上的显著关联(χ2 = 6.11，P = 0.013)，但这种关联在病例对照研究中未能复制。虽然与PCOS本身无关，但通过定量TDT分析，FTO中的5个SNP和MC4R中的2个SNP与BMI相关，其中几个SNP与病例对照队列中的BMI相关。这些发现表明，与肥胖相关的某些SNP导致多囊卵巢综合征患者BMI升高，但似乎对多囊卵巢综合征本身并不起主要作用。这些发现支持PCOS表型是少基因/多基因机制的结果的观点。
Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility in women. It is also associated with metabolic disturbances that place women at increased risk for obesity and type 2 diabetes. There is strong evidence for familial clustering of PCOS and a genetic predisposition. However, the gene(s) responsible for the PCOS phenotypes have not been elucidated. This two-phase family-based and case-control genetic study was designed to address the question of whether SNPs identified as susceptibility loci for obesity in genome-wide association studies (GWAS) are also associated with PCOS and elevated BMI. Members of 439 families having at least one offspring with PCOS were genotyped for 15 SNPs previously shown to be associated with obesity. Linkage and association with PCOS was assessed using the transmission/disequilibrium test (TDT). These SNPs were also analyzed in an independent case-control study involving 395 women with PCOS and 176 healthy women with regular menstrual cycles. Only one of these 15 SNPs (rs2815752 in NEGR1) was found to have a nominally significant association with PCOS (χ2 = 6.11, P = 0.013), but this association failed to replicate in the case-control study. While not associated with PCOS itself, five SNPs in FTO and two in MC4R were associated with BMI as assessed with a quantitative-TDT analysis, several of which replicated association with BMI in the case-control cohort. These findings demonstrate that certain SNPs associated with obesity contribute to elevated BMI in PCOS, but do not appear to play a major role in PCOS per se. These findings support the notion that PCOS phenotypes are a consequence of an oligogenic/polygenic mechanism.
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影响因子：
3.2
作者：
Barber, T. M.;McCarthy, M. I.;Franks, S.
通讯作者：
Franks, S.
影响因子：
30.8
作者：
Chambers, John C.;Elliott, Paul;Kooner, Jaspal S.
通讯作者：
Kooner, Jaspal S.
DOI：
10.1159/000264407
发表时间：
2010-01-01
期刊：
FRONTIERS IN EATING AND WEIGHT REGULATION
影响因子：
--
作者：
Hetherington, Marion M.;Cecil, Joanne E.
通讯作者：
Cecil, Joanne E.
影响因子：
9.8
作者：
Abecasis, GR;Cardon, LR;Cookson, WOC
通讯作者：
Cookson, WOC
影响因子：
5.8
作者：
Urbanek, M;Woodroffe, A;Spielman, RS
通讯作者：
Spielman, RS