Ethnic Differences in the Frequency of CFTR Gene Mutations in Populations of the European and North Caucasian Part of the Russian Federation

Abstract

Cystic fibrosis (CF) is a common monogenic disease caused by pathogenic variants in the CFTR gene. The distribution and frequency of CFTR variants vary in different countries and ethnic groups. The spectrum of pathogenic variants of the CFTR gene was previously studied in more than 1,500 CF patients from different regions of the European and North Caucasian region of Russia and the spectrum of the most frequent pathogenic variants of the CFTR gene and ethnic features of their distribution were determined. To assess the population frequency of CFTR gene mutations some of the common variants were analyzed in the samples of healthy unrelated individuals from the populations of the European part of the Russian Federation: 1,324 Russians from four European regions (Pskov, Tver, Rostov, and Kirov regions), representatives of five indigenous ethnic groups of the Volga-Ural region [Mari (n = 505), Udmurts (n = 613), Chuvash (n = 780), Tatars (n = 704), Bashkirs (n = 517)], and six ethnic groups of the North Caucasus [Karachay (n = 324), Nogais (n = 118), Circassians (n = 102), Abazins (n = 128), Ossetians (n = 310), and Chechens (n = 100)]. The frequency of common CFTR mutations was established in studied ethnic groups. The frequency of F508del mutation in Russians was found to be 0.0056 on average, varying between four regions, from 0.0027 in the Pskov region to 0.0069 in the Rostov region. Three variants W1282X, 1677delTA, and F508del were identified in the samples from the North Caucasian populations: in Karachay, the frequency of W1282X mutation was 0.0092, 1677delTA mutation – 0.0032; W1282X mutation in the Nogais sample – 0.0127, the frequency of F508del mutations was 0.0098 and 1677delTA – 0.0098 in Circassians; in Abazins F508del (0.0039), W1282X (0.0039) and 1677delTA (0.0117) mutations were found. In the indigenous peoples of the Volga-Ural region, the maximum frequency of the F508del mutation was detected in the Tatar population (0.099), while this mutation was never detected in the Mari and Bashkir populations. The E92K variant was found in Chuvash and Tatar populations. Thus, interethnic differences in the spectra of CFTR gene variants were shown both in CF patients and in healthy population of the European and North Caucasian part of Russia.

Identification of Pathogenic Variant Burden and Selection of Optimal Diagnostic Method Is a Way to Improve Carrier Screening for Autosomal Recessive Diseases

“…Furthermore, we performed a comparison of the obtained AF with those from recently published data for the Russian population [ 6 , 10 ]. There were no statistically significant differences in AF between our results and these two population studies, which is consistent with a close ethnic composition of studied groups of samples.…”

“…In addition, we compared our AF results to those in the known data for the Russian population, where available [ 6 , 10 ]. A total of six CFTR variants had AF for the Russian population ( n = 1324) in the study by Petrova et al [ 6 ]—rs121908751 (E92K), rs397508686 (L138ins), rs113993960 (F508del), rs121908776 (1677delTA), rs77010898 (W1282X), and hg19::chr7:117138367-117159446 (CFTRdele2,3). There were no statistically significant differences in AF compared to this study.…”

“…While expanded carrier screening with NGS is becoming more common, targeted testing approach remains a valid detection tool for the most widely distributed deleterious variants [ 3 ], especially in the case of variants, which account for a major part of the disease occurrence. There are no carrier screening programs in Russia, and the majority of the available panels [ 4 , 5 , 6 ] detect only a few variants most common for the disease. Besides there are only a limited number of studies with Russian population-based allele frequency (AF) data [ 6 , 7 , 8 , 9 , 10 ].…”

“…There are no carrier screening programs in Russia, and the majority of the available panels [ 4 , 5 , 6 ] detect only a few variants most common for the disease. Besides there are only a limited number of studies with Russian population-based allele frequency (AF) data [ 6 , 7 , 8 , 9 , 10 ].…”

“…To find a balance between the size of the panel (and therefore cost of screening) and the proportion of carriers it allows to detect, it is necessary to know the AF in the target population [ 6 ]. We designed a custom panel for carrier screening of the four aforementioned diseases consisting of 115 variants, which occur in the Russian population according to the literature data [ 4 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ].…”