印度北部人群哮喘和慢性胰腺炎病例中 CFTR 基因突变的谱和分布。

Spectrum and distribution of CFTR gene mutations in asthma and chronic pancreatitis cases of North Indian population.

机构信息

Deptarment of Medical Genetics, SGPGIMS, Lucknow 226014, India.

出版信息

Gene. 2014 Apr 10;539(1):125-31. doi: 10.1016/j.gene.2014.01.022. Epub 2014 Jan 14.

DOI:10.1016/j.gene.2014.01.022

PMID:24440239

Abstract

BACKGROUND

Cystic fibrosis transmembrane conductance regulator (CFTR) gene accounts for an autosomal recessive condition called cystic fibrosis (CF). In the Indian subcontinent, CF and its related diseases are under-diagnosed by the medical community due to poor knowledge of the disease and its confounding diagnosis, and also due to poor medical facilities available for these patients, thus causing an increased infant mortality rate with a low life expectancy in general. The aim of the study was to document the spectrum and distribution of CFTR mutations in controls, asthma and chronic pancreatitis cases of North India.

METHODS

A total of 800 subjects including 400 controls, 250 asthma cases and150 chronic pancreatitis cases were analyzed for 6 mutations (F508del, G542X, G551D, R117H, W1282X, and S549N) and IVS8 Tn polymorphism.

RESULTS

Out of 800 subjects, 18% [asthma - 24% (n=250), CP - 29.33% (n=150) cases and controls - 9.3% (n=400)] were positive for heterozygous mutation, 0.8% of the (n=250) asthmatic cases (n=250) were homozygous for IVS8 T5 polymorphism while no subjects were found positive for W1282X mutation. T5 polymorphism was more common in asthmatic cases while F508del mutation in chronic pancreatitis cases. The carrier frequency of F508del, G542X, G551D, R117H, S549N and T5 was 0.015, 0.025, 0.02, 0.005, 0.005, and 0.022 respectively. The cumulative carrier frequency was 0.093.

CONCLUSION

CFTR mutations were underestimated in Indian population. The present study will serve in establishment of genetic screening and prenatal setup for Indian population.

摘要

背景

囊性纤维化跨膜电导调节因子（CFTR）基因是一种常染色体隐性遗传病，称为囊性纤维化（CF）。在印度次大陆，由于对该疾病及其复杂诊断的了解不足，以及可供这些患者使用的医疗设施较差，医学界对 CF 和相关疾病的诊断不足，这导致婴儿死亡率增加，总体预期寿命较低。本研究的目的是记录印度北部 CFTR 突变在对照组、哮喘和慢性胰腺炎病例中的谱和分布。

方法

对 800 名受试者，包括 400 名对照、250 例哮喘病例和 150 例慢性胰腺炎病例，进行了 6 种突变（F508del、G542X、G551D、R117H、W1282X 和 S549N）和 IVS8 Tn 多态性分析。

结果

在 800 名受试者中，18%（哮喘-24%[n=250]、CP-29.33%[n=150]病例和对照组-9.3%[n=400]）为杂合突变阳性，250 例哮喘病例中有 0.8%（n=250）为 IVS8 T5 多态性纯合子，而未发现 W1282X 突变阳性。T5 多态性在哮喘病例中更为常见，而 F508del 突变在慢性胰腺炎病例中更为常见。F508del、G542X、G551D、R117H、S549N 和 T5 的携带频率分别为 0.015、0.025、0.02、0.005、0.005 和 0.022。累积携带频率为 0.093。