The methylenetetrahydrofolate reductase c.c.677 C>T and c.c.1298 A>C polymorphisms in reproductive failures: Experience from an RSA and RIF study on a Polish population

<div><p>Almost 1600 individuals from the Polish population were recruited to this study. Among them 319 were fertile couples, 289 were recurrent spontaneous abortion (RSA) couples, and 131 were in the group of recurrent implantation failure (RIF) following in vitro fertilization. The aim of this study was to evaluate the <i>MTHFR</i> c.c.677 C>T and c.c.1298 A>C polymorphisms’ association with RSA and RIF. We used PCR-RFLP with <i>Hinf</i>I (677 C>T) and <i>Mbo</i>II (1298 A>C) digestion. We observed a protective effect of the female AC genotype (OR = 0.64, <i>p</i> = 0.01) and the C allele (AC+CC genotypes; OR = 0.65, <i>p</i> = 0.009) against RSA. Moreover, 1298 AA/677 CT women were more frequent in RSA (31.14%) and RIF (25.20%) groups in comparison to fertile women (22.88%), although this difference was significant only in the case of RSA (<i>p</i> = 0.022, OR = 1.52). Male combined genotype analysis revealed no association with reproductive failure of their partners. Nevertheless, the female/male combination AA/AC of the 1298 polymorphism was more frequent in RSA couples (<i>p</i> = 0.049, OR = 1.49). However, the significant results became insignificant after Bonferroni correction. In addition, analysis of haplotypes showed significantly higher frequency of the C/C haplotype (1298 C/677 C) in the female control group than in the female RSA group (<i>p</i> = 0.03, OR = 0.77). Moreover, the association between elevated homocysteine (Hcy) level in plasma of RSA and RIF women and <i>MTHFR</i> polymorphisms was investigated but did not reveal significant differences. In conclusion, for clinical practice, it is better to check the homocysteine level in plasma and, if the Hcy level is increased, to recommend patients to take folic acid supplements rather than undergo screening of <i>MTHFR</i> for 1298 A>C and 677 C>T polymorphisms.</p></div

Distribution of genotypes in RSA and RIF groups according to the presence or absence of homocysteine (Hcy).

<p>Distribution of genotypes in RSA and RIF groups according to the presence or absence of homocysteine (Hcy).</p

Haplotype dependent association of rs7927894 (11q13.5) with atopic dermatitis and chronic allergic rhinitis: A study in ECAP cohort

<div><p>The T allele of rs7927894 (at 11q13.5) was associated with atopic dermatitis and other allergic diseases. Our purpose was to replicate the association with allergic phenotypes and explore the role of rs7927894 in predisposing to persistent allergic rhinitis and atopic asthma. We also wanted to explore if other SNPs at 11q13.5 contributed to effect of rs7927894. We studied patients with atopic dermatitis (N = 270), atopic asthma (N = 486), persistent allergic rhinitis (N = 589) and controls matched for age, sex and region (N = 540, N = 372 and N = 1178, respectively). We found that rs7927894 T was associated with atopic dermatitis (OR = 1.39, CI: 1.12–1.73, P = 0.003) and independently with persistent allergic rhinitis (OR = 1.24, CI:1.07–1.43, P = 0.0043, P_corrected = 0.013) but not atopic asthma. Analysis of additional tagging SNPs (rs7930763, rs2513517, rs7125552) showed that effect of rs7927894 T was limited to haplotypes encoding G at rs7125552. In conclusion, rs7927894 T is associated not only with atopic dermatitis but also persistent allergic rhinitis. Since these effects are haplotype dependent rs7927894 alone does not account for the association between 11q13.5 and atopic dermatitis/persistent allergic rhinitis.</p></div

Summary of the effects of <i>MTHFR</i> 1298 A>C and 677 C>T polymorphisms on susceptibility to RSA.

<p>Summary of the effects of <i>MTHFR</i> 1298 A>C and 677 C>T polymorphisms on susceptibility to RSA.</p

Characteristics of study population.

<p>Characteristics of study population.</p

Distribution of alleles and genotypes of rs7927894 among patients and controls.

<p>Distribution of alleles and genotypes of rs7927894 among patients and controls.</p

Distribution of genotypes of 11q13.5 SNPs among subjects with AD and controls.

<p>Distribution of genotypes of 11q13.5 SNPs among subjects with AD and controls.</p

Patient disposition according to initial calcineurine inhibitor use.

<p>AGR, acute graft rejection; CsA, cyclosporine A; Tac, Tacrolimus.</p

Linkage disequilibrium between <i>KIR2DS4</i> gene variants and <i>KIR2DS5</i> gene in patients and controls.

<p>Abbreviations: AGR, acute graft rejection; HFs, haplotype frequencies; D_KL, Kullback-Leibler divergence from linkage equilibrium; KIR, killer immunoglobulin-like receptor; <i>KIR2DS4fl</i>, <i>KIR2DS4</i> full length gene; <i>KIR2DS4del</i>, <i>KIR2DS4</i> 22-base pair deletion variant of the <i>KIR2DS4</i> gene; R², global squared correlation coefficient for two loci; r, correlation coefficient for alleles frequencies. <i>Likelihood ratio statistics</i> (LRS): {Pts with AGR} <i>vs</i> {Controls+Pts without AGR}; LRS = 11.01; <i>df</i> = 5; p = 0.0513.</p

<i>KIR</i> gene frequencies in controls and patients.

<p>Abbreviations: CI, confidence interval; KIR, killer immunoglobulin-like receptor; <i>KIR2DS4fl</i>, <i>KIR2DS4</i> full length gene; <i>KIR2DS4del</i>, <i>KIR2DS4</i> 22-base pair deletion variant of the <i>KIR2DS4</i> gene; OR, odds ratio.</p