男性不育患者Y染色体AZF区域STS微缺失位点多重PCR法检测及其意义

doi:10.13481/j.1671-587X.20230520

摘要/Abstract

摘要：

目的探讨Y染色体无精子症因子（AZF）区域的15个标签位点（STS）序列片段微缺失位点与男性不育（MI）的关系，为干预遗传性MI提供依据。方法选择2 586例疑似MI患者作为研究对象，按照年龄分为≤ 20岁组（14例）、21~30岁组（988例）、31~40岁组（1 318例）和≥41岁组（266例）。采用聚合酶链式反应（PCR）法对Y染色体AZF区域的15个STS序列片段进行检测并筛选异常结果，比较各组MI患者Y染色体微缺失情况。结果在2 586例参检人群样本中发现207例Y染色体异常，占总体样本的8.00%；其中≤20岁组、21~30岁组、31~40岁组和≥41岁组检出Y染色体异常率分别为7.14%（1/14）、8.10%（80/988）、8.04%（106/1 318）和7.52%（20/266）；各组患者基础位点合并扩展位点的缺失率比较差异有统计学意义（χ²=10.836，P=0.013），21~30岁组患者基础位点合并扩展位点的缺失率明显高于31~40岁组（P<0.05）；在总体受检样本中，发生基础位点片段缺失者52例，异常率为2.01%，各组患者异常率比较差异有统计学意义（χ²=9.658，P=0.022）；AZFc片段缺失者占所有受检人数1.39%，21~30岁组和31~40岁组患者AZFc缺失率明显高于≥41岁组（P<0.05），21~30岁组和31~40岁组患者总体缺失率比较差异有统计学意义（χ²=3.612，P=0.040）；各组患者sY127、sY134合并sY105、sY121、sY1192、sY153和sY160位点缺失率比较差异无统计学意义（P>0.05），各组患者sY254、sY255合并sY105、sY121、sY1192、sY153和sY160位点缺失率比较差异无统计学意义（P>0.05）结论广西壮族自治区东北部地区主要生育年龄段男性Y染色体异常的主要原因是sY1192和sY153位点微缺失，其中以sY1192位点微缺失为主，且随着年龄增长，该位点突变检出率越高。

关键词: 男性不育, Y染色体, 微缺失位点, 标签位点, 无精子症因子

Abstract:

Objective To discuss the relationship between microdeletions of 15 sequence tagged sites （STS） in azoospermia factor （AZF） region of the Y chromosome and male infertility （MI）， and to provide the evidence for the intervention of hereditary MI. Methods A total of 2 586 suspected MI patients were selected， and they were divided into four groups according to their ages，≤20 years old group（14 cases）， 21—30 years old group（988 cases）， 31—40 years old group（1 318 cases），and ≥41 years old group（266 cases）. The polymerase chain reaction （PCR） method was used to detect the 15 STS sequence fragments in the Y chromosome AZF region and the abnormal results were screened out. The microdeletion status of the Y chromosome was compared among the MI patients in various groups. Results Among 2 586 samples， 207 cases of Y chromosome abnormalities were found， accounting for 8.00% （207/2 586） of the total samples. The Y chromosome abnormalit rates of the somples in≤20 years old， 21—30 years old，31—40 years old， and ≥41 years old groups were 7.14% （1/14）， 8.10% （80/988），8.04% （106/1 318）， and 7.52% （20/266）， respectively； there were significant differences in the detetion rates of base sites and extension sites of the patients between various groups （χ²=10.836，P=0.013），and the deletion rate of base sites and extension sites of the patients in 21—30 years old group was higher than that in 31—40 years old group （P<0.05）. In the overall tested samples， 52 cases of base site fragment deletion were found， the abnormality rate was 2.01%， and there were significant differences in the abnormality rates of the patients between various groups （χ²=9.658， P=0.022）. The deletion rate of the AZFc segment accounted for 1.39% of all tested individuals， and the deletion rates of the patients in 21—30 years old group and 31—40 years old group were significantly higher than that in ≥41 years old group （P<0.05）.There were significant differences in the overall deletion rates of the patients between 21—30 years old and 31—40 years old groups（χ²=3.612，P=0.040）. There were no statistically significant differences in the deletion rates of the sY127， sY134 combined with sY105， sY121， sY1192， sY153， and sY160 sites of the patients between various groups （P>0.05），and there were no significant differences in the deletion rates of the sY254， sY255 combined with sY105， sY121， sY1192， sY153， and sY160 sites of the patients between various groups （P>0.05）. Conclusion The main cause of Y chromosome abnormalities of the males in reproductive age group in Northeast of Guangxi Zhuang Autonomous Region is microdeletion at the sY1192 and sY153 sites， and the sY1192 site microdeletion is the most prevalent. The detection rate of mutation at this site is increased with the increasing of age.

Key words: Male infertility, Y chromosome, Microdeletion site, Tag site, Azoospermia factor

中图分类号:

R394.1

冯乔,王曼伊,于鸿浩,李君,曾丹,侯任. 男性不育患者Y染色体AZF区域STS微缺失位点多重PCR法检测及其意义[J]. 吉林大学学报(医学版), 2023, 49(5): 1262-1267.

Qiao FENG,Manyi WANG,Honghao YU,Jun LI,Dan ZENG,Ren HOU. Multiplex PCR method detection of STS microdeletion sites in AZF region of Y chromosome in male infertility patients and its significance[J]. Journal of Jilin University(Medicine Edition), 2023, 49(5): 1262-1267.

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参考文献 22

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Group	Microdeletion region			Total
Group	Base site and extension site	Base site	Extension site	Total
≤ 20 years old	1(7.14)	0(0)	0(0)	1(7.14)
21－30 years old	28(2.83)	0(0)	52(5.26)	80(8.10)
31－40 years old	20(1.52)	2(1.52)	84(6.37)	106(8.04)
≥ 41 years old	1(0.38)	0(0)	19(7.14)	20(7.52)
Total	50(1.93)	2(0.08)	155(5.99)	207(8.00)
χ²	10.836	1.926	2.789	0.113
P	0.013	0.588	0.452	0.990

Group	AZF missing region					Total
Group	AZFa	AZFb	AZFc	AZFb+AZFc	AZFa+AZFb+AZFc	Total
≤ 20 years old	0(0)	0(0)	1(7.14)	0(0)	0(0)	1(7.14)
21－30 years old	1(0.10)	2(0.20)	19(1.92)	4(0.40)	2(0.20)	28(2.83)
31－40 years old	0(0)	1(0.08)	15(1.14)	6(0.46)	0(0)	22(1.67)
≥ 41 years old	0(0)	0(0)	1(0.38)	0(0)	0(0)	1(0.38)
Total	1(0.04)	3(0.12)	36(1.39)	10(0.39)	2(0.08)	52(2.01)
χ²	5.541	3.323	8.022	1.811	5.389	9.658
P	0.490	0.702	0.048	0.820	0.351	0.022

Group	AZFc abnormal fragments				Total
Group	sY254(－)/sY255(－),Y1192(－)/sY143(－),sY153(－)	sY153(－)	sY1192(－)/sY143(－)	sY1192(－)/sY143(－),sY153(－)	Total
≤ 20 years old	1(7.14)	0(0)	0 (0)	0(0)	1(7.14)
21－30 years old	19(1.92)	2(0.20)	40(4.05)	10(1.01)	71(7.19)
31－40 years old	15(1.14)	0(0)	63(4.78)	21(1.59)	99(7.51)
≥ 41 years old	1(0.38)	0(0)	15(5.64)	4(1.50)	20(7.52)
Total	36(1.39)	2(0.08)	118(4.56)	35(1.35)	191(7.39)
χ²	8.022	5.389	1.535	1.785	0.247
P	0.048	0.351	0.623	0.566	0.983

Group	Number of abnormal fragment			Total
Group	sY127(－),sY134(－),sY254(－),sY255(－), sY121(－),sY1192(－)/sY143(－),sY153(－)	sY127(－),sY134(－),sY254(－),sY255(－), sY121(－),sY1192(－)/sY143(－), sY153(－),sY160(－)	sY127(－),sY134(－),sY254(－),sY255(－),sY121(－),sY1192(－)/sY143(－),sY153(－),sY160(－),sY105(－)	Total
≤ 20 years old	0(0)	0(0)	0(0)	0(0)
21－30 years old	3(0.30)	1(0.10)	0(0)	4(0.40)
31－40 years old	3(0.23)	1(0.08)	2(0.15)	6(0.46)
≥ 41 years old	0(0)	0(0)	0(0)	0(0)
Total	6(0.23)	2(0.08)	2(0.08)	10(0.39)
χ²	2.072	3.424	4.234	1.811
P	0.852	1.000	0.610	0.833

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