Mutational analysis of minichromosome maintenance complex component (MCM) family genes in Chinese Han women with polycystic ovarian syndrome

Figures & data

Table 1. Clinical data of the patients.

Variable	PCOS (n = 365)	Control (n = 860)	p value^a
Age (y)	28.28 ± 3.76	28.91 ± 6.74	.5364
BMI (kg/m^2)	27.60 ± 3.26	25.42 ± 3.51	<.001
FSH (IU/L)	5.81 ± 1.40	6.51 ± 4.80	<.001
LH (IU/L)	9.58 ± 10.34	8.92 ± 5.84	.3360
E2 (pg/mL)	149.40 ± 63.39	126.04 ± 101.17	.3280
T (ng/dL)	40.72 ± 19.02	30.44 ± 10.87	<.001
P (ng/mL)	1.06 ± 1.48	1.89 ± 4.60	.2424
AMH (ng/mL)	7.73 ± 4.03	2.53 ± 2.33	<.001

Data are given as mean ± SD.

BMI, body mass index; FSH, follicle-stimulating hormone; LH, luteinizing hormone; E2, estradiol; P, progesterone; T, testosterone; SD, standard deviation.

^a p values obtained by comparison of variables between PCOS and control groups using the Mann–Whitney U test.

Figure 1. The sequence chromatograms of MCM family genes variations identified in Chinese patients with PCOS. The arrow refers to the location of the mutation, compared with normal control sequences.

Figure 2. The schematic diagram of the MCM family genes. The arrow refers to the location of the mutations identified in patients with PCOS. The red arrows show the novel mutations identified in our study.

Table 2. Genetic variants of MCM gene family.

Gene/ Transcript	Patient	Rs#	Base change	Protein change	SIFT	PolyPhen2	MAF in 365 PCOS patients	MAF in 860 controls	p value (cont rol-PCOS)	MAF in TOPMED	MAF in ExAC
MCM2 NM_004526.3	GB143, GB320	rs1852298481	53G > C	Arg18Pro	0.007(D)	0.916(D)	0.0027 (2/730)	0 (0/1720)	.0893	NP	NP
	GB301	rs775995747	389G > A	Arg130His	0.009(D)	0.956(D)	0.0014 (1/730)	0 (0/1720)	.2985	0.000008	0.000046
	GB363	Novel	20C > G	Ser7Cys	0.009(D)	0.635(P)	0.0014 (1/730)	0 (0/1720)	.2985	NP	NP
	GB415	rs138684820	1888G > A	Ala630Thr	0.001(D)	0.869(P)	0.0014 (1/730)	0.0047(8/1720)	.2950	0.000135	0.000359
	GB496	rs762194625	2420A > G	Lys807Arg	0.014(D)	0.984(D)	0.0014 (1/730)	0 (0/1720)	.2985	0.000104	0.000118
MCM4 NM_005914.3	GB75	rs548816846	571C > T	Pro191Ser	0.02(D)	0.961(D)	0.0014 (1/730)	0 (0/1720)	.2985	0.000072	0.000091
	GB255, GB383	rs151044076	1829G > A	Arg610His	0.0(D)	0.993(D)	0.0027 (2/730)	0.0023(4/1720)	1.0000	0.000247	0.000354
	GB480	rs756593226	2122C > T	Gln708*	–	–	0.0014 (1/730)	0 (0/1720)	.2985	0.000024	0.000044
	GB445	rs556503441	2243G > A	Arg748Lys	0.0(D)	0.999(D)	0.0014 (1/730)	0.0006 (1/1720)	.5078	0.000032	0.000066
MCM5 NM_006739.3	GB309	rs142715814	553C > T	Arg185Cys	0.027(D)	0.696(P)	0.0014 (1/730)	0 (0/1720)	.2985	0.000119	NP
	GB370	rs7702227185	995A > G	Try332Cys	0.001(D)	0.11(B)	0.0014 (1/730)	0 (0/1720)	.2985	NP	NP
	GB492	Novel	1049A > G	Lys350Arg	0.001(D)	0.994(D)	0.0014 (1/730)	0 (0/1720)	.2985	NP	NP
	GB423	rs1028271579	1789G > A	Glu597Lys	0.004(D)	0.85(P)	0.0014 (1/730)	0 (0/1720)	.2985	0.000016	NP
MCM6 NM_005915.5	GB321	rs765220170	620G > A	Arg207His	0.001(D)	0.993(D)	0.0014 (1/730)	0.0006 (1/1720)	.5078	0.000032	0.000017
MCM7 NM_005916.4	GB474	rs376400426	644G > A	Arg215His	0.07(D)	0.639(P)	0.0014 (1/730)	0 (0/1720)	.2985	0.000072	0.000082
	GB481	rs765220170	1219C > T	Arg407Trp	0.0(D)	1.0(D)	0.0014 (1/730)	0.0006 (1/1720)	.5078	0.000032	0.000017
	GB429	rs1443365468	1579C > T	Arg527*	–	–	0.0014 (1/730)	0.0012 (2/1720)	1.0000	NP	NP
MCM8 NM_001281521.1	GB346	rs146490315	832C > T	Arg278Cys	0.042(D)	0.742(P)	0.0014 (1/730)	0 (0/1720)	.2985	0.000175	0.000346
	GB328	rs201813827	1565C > T	Thr522Met	0.001(D)	0.873(P)	0.0014 (1/730)	0 (0/1720)	.2985	0.000064	0.000082
MCM9 NM_017696.2	GB387	rs367896634	395G > A	Arg132Gln	0.0(D)	0.997(D)	0.0014 (1/730)	0 (0/1720)	.2985	0.000096	0.000074
MCM10 NM_182751.2	GB275, GB427	rs780031747	136T > G	Phe46Val	0.0(D)	0.996(D)	0.0027 (2/730)	0 (0/1720)	.0893	0.000016	0.000016
	GB390	Novel	849G > T	Lys283Asn	0.026(D)	0.864(P)	0.0014 (1/730)	0 (0/1720)	.2985	NP	NP
MCMDC2 NM_173518.4	GB306	rs369484487	530C > T	Thr177Met	0.003(D)	0.928(D)	0.0014 (1/730)	0 (0/1720)	.2985	0.000032	NP
MCM3AP NM_003906.4	GB97, GB329	rs144496882	4867G > A	Val623Met	0.011(D)	0.921(D)	0.0027 (2/730)	0.0029 (5/1720)	1.0000	0.000104	0.000082
	GB342, GB390	rs17183290	5383G > A	Ala1795Thr	0.01(D)	0.996(D)	0.0027 (2/730)	0.0035 (6/1720)	1.0000	0.000247	0.000338
	GB445	Novel	5123C > T	Ser1708Phe	0.003(D)	0.963(D)	0.0014 (1/730)	0 (0/1720)	.2985	NP	NP
	GB440	rs201315959	2653C > T	Leu885Phe	0.007(D)	0.997(D)	0.0014 (1/730)	0.0029 (5/1720)	.6769	0.000223	0.000098
	GB443	rs781537531	3746C > A	Ala1249Asp	0.01(D)	0.621(P)	0.0014 (1/730)	0 (0/1720)	.2985	0.000008	0.000011
	GB370, GB391, GB446, GB207	rs199529702	2524C > G	Gln842Glu	0.014(D)	0.133(B)	0.0055 (4/730)	0.0006 (1/1720)	.0294	0.000032	0.000032

NP, not present in the database; D, probably damaging; P, possibly damaging; B, benign.

Figure 3. The evolutionary conservation analysis of the four novel mutations in the MCM family genes. These results suggested that these mutations were highly conserved among 10 vertebrate species from Human to Pig.

Figure 4. Structural difference between wild type and mutant type proteins. The proteins structural of wild type and mutany type were modeled based on the crystal model of human MCM5 and MCM10 proteins, respectively. The enlarged image shows that both the MCM5 p.K350R and MCM10 p.K283N mutations caused the structure changes of MCM5 and MCM10 protein, respectively.

Availability of data and materials

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