RF6基因多态性与黔北人群非综合征性唇腭裂的相关性研究

目的 探讨黔北地区人群IRF6基因rs2235371和rs2235373 SNP位点的多态性及其与非综合征性唇腭裂的相关性。方法 采用PCR和测序方法对153个对照儿童和123个NSCL/P儿童的IRF6基因中2个SNP位点rs2235371和rs2235373进行扩增和测序；对样本群体进行Hardy-Weinberg平衡分析，比较2组人群的基因型频率、等位基因频率及OR分析；两位点连锁不平衡分析。结果 对照组与病例组人群rs2235371基因型均含有GG、GA和AA型，rs2235373位点均含有CC、CT和TT型。对于2个位点，对照组和病例组均符合Hardy-Weinberg平衡法则(P＞0.05)。2组人群中，rs2235371和rs2235373位点的等位基因和基因型差异均有统计学意义(P＜0.05)；rs2235371位点GGvsGA的OR值(95%CI) =1.725(1.025～2.902)，GGvsAA的OR值(95%CI) = 2.100(1.109～4.328)；rs2235373位点CCvsTT的OR值(95%CI) = 2.263(1.348～5.015)，CTvsTT的OR值(95%CI) = 2.061(1.108～2.169)；(P＜0.05)。rs2235371和rs2235373位点存在连锁不平衡，GC单倍型是主要的单倍体型，对NSCL/P均有致病风险，OR值(95%CI)= 1.722(1.219～2.431)， (P＜0.05)。结论 在黔北地区人群中，IRF6基因 rs2235371和rs2235373位点均具有多态性；rs2235371位点的GG基因型和rs2235373位点的CC、CT基因型与NSCL/P的发生有相关性；rs2235371和rs2235373位点存在连锁不平衡，GC单倍型对NSCL/P有致病风险。

Correlation study of polymorphism of IRF6 gene and nonsyndromic clepft lip with or without cleft in north of Guizhou

Objective To study the correlation between SNP sites rs2235371 and rs2235373 of IRF6 gene and nonsyndromic clepft lip with or without cleft in north of Guizhou. Methods PCR and DNA sequencing technology were used to detect the SNP sites in the IRF6 gene in 153 children without NSCL/P(control group) and 123 children with NSCL/P(case group). Two groups were performed Hardy-Weinberg test, Genotype frequencies analyses, allele frequencies analyses and odd ration analyses. Linkage disequilibrium analysis was performed on rs2235371 and rs2235373. Results SNP rs2235371 contained GG, GA and AA genetypes while SNP rs2235373 contained CC, CT and TT genetypes in both groups. The two groups were in line with the principles of Hardy-Weinberg equilibrium (P>0.05). The difference of frequencies of genotype and allele in two SNP sites between two groups were statistically significant (P<0.05). In rs2235371 site, OR (95%CI) of GGvsGA=1.725 (1.025-2.902) and OR (95%CI) of GGvsAA=2.100 (1.109-4.328). In rs2235373site, OR (95%CI) of CCvsTT=2.263 (1.348-5.015) and OR (95%CI) of CTvsTT=2.061 (1.108-2.169). There was linkage disequilibrium between rs2235371 and rs2235373. GC haplotype was the main haplotype and be risk to NSCL/P, OR(95%CI)=1.722(1.219-2.431)(P<0.05). Conclusion Polymorphism exists in rs2235371 and rs2235373 in the people from north of Guizhou. GG genetype of rs2235371 is related to NSCL/P. CC and CT genetype of rs2235373 is related to NSCL/P. There is linkage disequilibrium between rs2235371 and rs2235373 of IRF6 gene. GC haplotype is risk to NSCL/P.