Dataset of allele, genotype and haplotype frequencies of four polymorphisms filaggrin gene in Russian patients with atopic dermatitis.

Data on the allele, genotype and haplotype frequencies of four single nucleotide polymorphisms (SNPs) (rs3126085, rs12144049, rs471144 and rs4363385) filaggrin (FLG) gene in Russian patients with atopic dermatitis are presented. Genome-wide association studies identified these SNPs could be significant genetic markers associated with atopic dermatitis. The frequencies of alleles, genotypes and haplotypes of four SNPs were calculated in 3 groups: entire sample, females and males. No significant differences in the allele, genotype and haplotype frequencies between males and females with AD patients were observed.

Data description

The dataset represents the raw data (supplementary Table), frequencies of alleles, genotypes (Table 1) and haplotypes (Fig. 1, Table 2) for four single nucleotide polymorphisms (SNPs) (rs3126085, rs12144049, rs471144 and rs4363385) filaggrin (FLG) gene in Russian patients with atopic dermatitis (AD). These SNPs were associated with AD in previously published genome-wide association studies (GWAS) (Table 3) and also candidate gene studies https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738205/ [[1], [2], [3], [4], [5]], have significant regulatory potential (Table 4) and influence gene expression level (Table 5). The dataset frequencies of the SNP alleles, genotypes and haplotypes were divided into three groups: entire sample, females and males. The minor allele frequency (MAF) for rs3126085 – 0.1443 (female – 0.1477, male – 0.1372), rs12144049 – 0.2300 (female – 0.2363, male – 0.2168), rs471144 – 0.0714 (female – 0.0823, male – 0.0487) and rs4363385 – 0.4243 (female – 0.4283, male – 0.4159). No significant differences in the allele, genotype and haplotype frequencies were found between males and females with AD patients.

Table 1

The frequencies of alleles and genotypes for single nucleotide polymorphisms (SNPs) rs3126085, rs12144049, rs471144 and rs4363385 in FLG gene in Russian patients with atopic dermatitis.

SNP genotype or allele	All (n = 350)		Female (n = 237)		Male (n = 113)
	n	frequency	n	frequency	n	frequency
rs3126085
AA	12	0.0342	9	0.0380	3	0.0265
GA	77	0.2200	52	0.2194	25	0.2212
GG	261	0.7457	176	0.7426	85	0.7522
A	101	0.1443	70	0.1477	31	0.1372
G	599	0.8557	404	0.8523	195	0.8628
rs12144049
GG	26	0.0743	18	0.0759	8	0.0708
AG	109	0.3114	76	0.3207	33	0.2920
AA	215	0.6143	143	0.6034	72	0.6372
G	161	0.2300	112	0.2363	49	0.2168
A	539	0.7700	362	0.7637	177	0.7832
rs471144
TT	4	0.0114	4	0.0169	0	0.0000
GT	42	0.1200	31	0.1308	11	0.0973
GG	304	0.8686	202	0.8523	102	0.9027
T	50	0.0714	39	0.0823	11	0.0487
G	650	0.9286	435	0.9177	215	0.9513
rs4363385
AA	66	0.1886	45	0.1899	21	0.1858
GA	165	0.4714	113	0.4768	52	0.4602
GG	119	0.3400	79	0.3333	40	0.3540
A	297	0.4243	203	0.4283	94	0.4159
G	403	0.5757	271	0.5717	132	0.5841

Fig. 1

Linkage disequilibrium (LD) between SNPs rs3126085, rs12144049, rs471144, and rs4363385 of the FLG gene in Russian patients with atopic dermatitis. LD measures are presented as Lewontin's standardized coefficient D′ (Figure, A) and the square of the correlation Pearson's coefficient (r2) between SNPs (Figure, B). D′ values vary gradually from white color (D′ = 0, no LD between SNPs) to dark red (D′ = 1, SNPs are in complete LD). Figure sections 1, 2 and 3 represent entire sample, females, and males, respectively.

Table 2

The frequencies of haplotypes for haploblock of single nucleotide polymorphisms (SNPs) rs3126085 and rs12144049 in FLG gene in Russian patients with atopic dermatitis.

Haplotype (rs3126085 and rs12144049)	All (n = 350), frequency	Female (n = 237), frequency	Male (n = 113), frequency
GA	0.638	0.626	0.656
GG	0.224	0.232	0.212
AA	0.138	0.142	0.132

Table 3

The literature data about associations of the studied polymorphisms with atopic dermatitis (GWAS data).

SNP	Position (hg38)	Association (significance)	Reference
rs3126085	152,328,341	OR = 1.22 (p = 6 × 10−12)	[1]
rs12144049	152,468,434	OR = 1.53 (p = 3 × 10−30)	[2]
		OR = 1.39 (p = 1 × 10−16)	[3]
rs471144	152,481,779	OR = 1.54 (p = 2 × 10−12)	[2]
rs4363385	153,016,845	OR = 1.23 (p = 2 × 10−17)	[2]

Table 4

Regulatory effects of the 4 SNPs of the FLG gene (HaploReg, v4.1, update 05.11.2015) (https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php).

chr	pos (hg38)	variant	Ref	Alt	AFR	AMR	ASN	EUR	SiPhy	Promoter	Enhancer	DNAse	Proteins	Motifs	NHGRI/EBI	GRASP QTL	Selected eQTL	GENCODE	dbSNP
					freq	freq	freq	freq	cons	histone marks	histone marks		bound	changed	GWAS hits	hits	hits	genes	func annot
1	152328341	rs3126085	G	A	0.53	0.36	0.59	0.15			7 tissues			Foxp3,TEF	1 hit	1 hit	26 hits	FLG-AS1	intronic
1	152468434	rs12144049	C	T	0.67	0.8	0.76	0.74						Irf,Obox6,ZEB1		2 hits	1 hit	23kb 3′ of RP1-91G5.3
1	152481779	rs471144	T	G	0.06	0.08	0.18	0.08		LIV, GI				7 altered motifs			1 hit	29kb 5′ of LCE5A
1	153016845	rs4363385	T	C	0.78	0.54	0.66	0.59								3 hits	7 hits	4.2kb 5′ of SNORA31

Table 5

The cis-eQTL values of the 4 SNPs of the FLG gene in skin (according to Genotype-Tissue Expression (GTEx) (http://www.gtexportal.org/)).

SNP	Gene expression	Reference allele	Alternative allele	Effect Size (β)	P-Value	Tissue
rs3126085	FLG	G	A	−0.22	0.000000037	Skin - Sun Exposed (Lower leg)
	RP1-91G5.3	G	A	0.38	0.00002	Skin - Sun Exposed (Lower leg)
rs12144049	CRNN	C	T	−0.3	0.00000000096	Skin - Sun Exposed (Lower leg)
	CRNN	C	T	−0.32	0.00000003	Skin - Not Sun Exposed (Suprapubic)
rs471144	FLG-AS1	T	G	−0.51	0.000023	Skin - Not Sun Exposed (Suprapubic)
rs4363385	SPRR1B	T	C	−0.25	0.00000000011	Skin - Sun Exposed (Lower leg)
	SPRR2D	T	C	0.27	0.0000000045	Skin - Sun Exposed (Lower leg)
	LCE3C	T	C	−0.34	0.000000033	Skin - Sun Exposed (Lower leg)
	LCE3C	T	C	−0.34	0.000000033	Skin - Not Sun Exposed (Suprapubic)
	SPRR2B	T	C	−0.24	0.00000081	Skin - Sun Exposed (Lower leg)
	LCE1D	T	C	−0.27	0.0000014	Skin - Not Sun Exposed (Suprapubic)
	SPRR1B	T	C	−0.18	0.0000025	Skin - Not Sun Exposed (Suprapubic)
	LCE1D	T	C	−0.24	0.0000046	Skin - Sun Exposed (Lower leg)
	SPRR2B	T	C	−0.24	0.000014	Skin - Not Sun Exposed (Suprapubic)

Experimental design, materials, and methods

Subjects selection

During a period between 2010 and 2016, AD patients were recruited at Dermatovenerologic dispensaries of Belgorod and Kursk regions (Russia). AD was diagnosed by experienced dermatologists according to the UK Diagnostic Criteria [6]. The participants were unrelated Russians born in the Central Russia [7]. The exclusion criteria were as follows: malignant tumors, severe autoimmune diseases, chronic severe diseases of the vital organs (heart, respiratory or renal failure). A total of 350 patients with AD (237 female and 113 male) met these criteria. This work was approved by the Regional Ethics Committee of Belgorod State University and informed consents were obtained from all participants.

DNA analysis

The procedures of whole blood sampling, genomic DNA isolation were described elsewhere [8].

Four SNPs in the FLG gene such as rs3126085, rs12144049, rs471144 and rs4363385 were selected for the analysis according to the following criteria [9]: 1) a SNP was reported to be associated with AD risk by genome-wide association, 2) SNP possesses a regulatory potential (regSNP), 3) SNP is associated with changes in gene expression (eSNP), and 4) MAF ≥ 5%.

The selected SNPs were found to be associated with the risk of AD, as previously reported by genome-wide association studies (Table 3) and were found to be functionally significant polymorphisms, i.e. they possess significant regulatory potential (Table 4), as determined by the HaploReg online tools, v4.1 update 05.11.2015 (https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php), and have impact on gene expression level (Table 5), as determined by the GTExportal, (http://www.gtexportal.org).

DNA samples were genotyped using the MALDI-TOF mass spectrometry iPLEX platform (Agena Bioscience Inc, San Diego, CA). To ensure quality control of genotyping blind replicates were included. Laboratory personnel involved in genotyping were completely blinded to patients’ information. The repeatability test for 5% of randomly selected samples was performed, yielded 100% reproducibility.

Statistical analysis

Genotypes for the polymorphisms were evaluated regarding their accordance to Hardy-Weinberg equilibrium (HWE) using the chi-square test. Differences in allele, genotype and haplotype frequencies between females and males with AD were assessed by the Kruskall-Wallis test. The linkage disequilibrium (LD) between rs3126085, rs12144049, rs471144 and rs4363385 FLG gene was analyzed using Haploview version 4.2 software (https://www.broadinstitute.org/haploview/haploview). The LD block structure was determined using the Solid Spine of the LD algorithm [10] provided by the Haploview 4.2. The degree of genetic linkage between the 4 SNPs in 3 groups was estimated as Lewontin's coefficient D′ and squared Pearson's correlation coefficient r2. D′ values vary gradually from white color (D′ = 0, no LD between SNPs) to dark red (D′ = 1, SNPs are in complete LD). (Fig. 1).

Specifications Table

Subject	Biology
Specific subject area	Genetics
Type of data	Table and figure
How data were acquired	MALDI/TOF mass spectrometry using Sequenom MassARRAY 4.0 platform (Agena Bioscience™)
Data format	Raw and analyzed data
Parameters for data collection	Total genomic DNA was isolated from buffy coat using the standard phenol-chloroform method.
Description of data collection	DNA samples were genotyped using the Sequenom MassARRAY® iPLEX platform, which is based on MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry
Data source location	Belgorod, Russia
Data accessibility	The data is available with this article

Value of the Data• The frequencies of alleles, genotypes and haplotypes of rs3126085, rs12144049, rs471144 and rs4363385 of the FLG gene in Russian were not differed between males and females with AD. • The polymorphisms at the FLG gene may associate with atopic dermatitis. • The allele, genotype and haplotype frequencies are an important data for understanding the genetic architecture of different populations. • The data can be used for studying the genetic basis of atopic dermatitis and other skin (i.e. psoriasis) or allergic disease (i.e. asthma) in various populations of the world.